A170566 Study Report Body

Clinical Study Report
Protocol No.: A17.0566

Page 1 of 79
1.0 TITLE PAGE
An open label, randomized, two-treatment, two-sequence,

two-period, cross over, single-dose, oral bioequivalence
study of Lisdexamfetamine Dimesylate Capsules 70 mg
Study Title : (Test) of Norwich Pharmaceuticals, Inc. and Vyvanse®
(Lisdexamfetamine Dimesylate) Capsules 70 mg (Reference)
of Shire US Inc., in healthy, adult, human subjects under
fasting conditions.
Investigational Medicinal Product
Reference Product (R) : Vyvanse® (Lisdexamfetamine Dimesylate) Capsules 70 mg
Test Product (T) : Lisdexamfetamine Dimesylate Capsules 70 mg
Vyvanse® is indicated for the treatment of Attention Deficit
Indication : Hyperactivity Disorder (ADHD) and Moderate to Severe
Binge Eating Disorder (BED) in adults.
An open label, randomized, two-treatment, two-sequence,
two-period, cross-over, single-dose, oral bioequivalence
Study Design :
study in healthy, adult, human subjects under fasting
conditions.
Name of the Sponsor : Norwich Pharmaceuticals, Inc.
Protocol Identification
: A17.0566 (Version No.: 01, Dated: 12MAR19)
Number
Development Phase of
: I (Bioequivalence Study)
Study
Study Dates
Date of First Subject
: 27APR19
Enrolled
Date of Last Subject
: 08MAY19
Completed
Peter C. Boldingh, Pharm.D., R.Ph.
AXIS Clinicals
Principal Investigator : 1711 Center Avenue West
Dilworth, MN 56529-1342
Telephone No.: 218-284-9844
K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc
Page 2 of 79
Email: P.Boldingh@AxisClinicals.com
Meena Venugopal, Ph.D.
Norwich Pharmaceuticals, Inc.
10B Bloomfield Avenue
Sponsor
: Pine Brook, New Jersey 07058, USA
Representative
Fax No.: 973-227-6556
Email: Meena.Venugopal@alvogen.com
Good Clinical Practice Statement: This study was conducted as per the protocol, ICH-
GCP guidelines and SOPs of AXIS Clinicals (refer to Appendix 16.1.5 for GCP
compliance statement).
All drug accountability records, case report forms (CRFs), source data, and related
regulatory documents will be retained for at least two years following marketing
approval.
Report Issued : 11JUL19

Page 3 of 79
1.1 Signature Page
We attest to the fact that the data presented here is accurate and reflects the raw data. The
study has been conducted as per the protocol, SOPs of AXIS Clinicals and all other
pertinent requirements of the ICH ‘Guideline for Good Clinical Practice’ and ‘FDA
bioanalytical guidance’, Code of Federal Regulations (21 CFR), Parts 50, 54, 56, 312, 314,
and 320, and applicable regulatory requirements. We accept the responsibility for scientific
correctness of the project and the validity of the data produced in this report.
__________________________ __________________
Peter C. Boldingh, Pharm.D., R.Ph. Date
Principal Investigator
___________________________ __________________
Ardeshir Khadang Date
Bioanalytical Investigator

Page 4 of 79
2.0 SYNOPSIS
Name of Sponsor / Company: Individual study table (for national

referring to part of the authority use only)
dossier
Name of Finished Product:
Lisdexamfetamine Dimesylate Capsules 70
mg
Name of Active Ingredient: Volume: 01
Lisdexamfetamine
Title of Study: An open label, randomized, two-treatment, two-sequence, two-period, cross
over, single-dose, oral bioequivalence study of Lisdexamfetamine Dimesylate Capsules 70 mg
(Test) of Norwich Pharmaceuticals, Inc. and Vyvanse® (Lisdexamfetamine Dimesylate)
Capsules 70 mg (Reference) of Shire US Inc., in healthy, adult, human subjects under fasting
conditions.
Investigators:
Principal Investigator: Peter C. Boldingh, Pharm.D., R.Ph.
Sub-Investigators: Patrick A. Luger, M.D.; Brent Gillund, MA, CCRC.; and Harry
Moskowitz
Bioanalytical Investigator: Ardeshir Khadang, BS Analytical Chemistry
Statistical Investigator: Rakesh.P, M.Sc. Statistics
Study Center(s):
Clinical : AXIS Clinicals
1711 Center Avenue West
Bioanalytical : AXIS Clinicals
1711 Center Avenue West
Statistical : AXIS Clinicals LLC, Offshore Office
1-121/1, Miyapur,
Hyderabad-500 049, India
Telephone No.:+91-40-40408158

Page 5 of 79

dossier
mg
Lisdexamfetamine
Publication (Reference): None at the time of this report.
Study Period: Phase of Development: Phase I
Date of First Enrollment: 27APR19 Type of Study: Bioequivalence Study
Date of Completion: 08MAY19
Objectives:
Primary Objective:
To compare the rate and extent of absorption of Lisdexamfetamine Dimesylate Capsules 70 mg
(Test) of Norwich Pharmaceuticals, Inc. with Vyvanse® (Lisdexamfetamine Dimesylate)
Capsules 70 mg (Reference) of Shire US Inc., under fasting conditions.
Secondary Objective:
To monitor for adverse events and optimize subject safety.
Methodology: An open label, randomized, two-treatment, two-sequence, two-period,
cross-over, single-dose, oral bioequivalence study in healthy, adult, human subjects under
fasting conditions. A total of twenty-eight (28) subjects were enrolled in the study in order to
ensure twenty-eight (28) subjects to be dosed with Lisdexamfetamine Dimesylate Capsules 70
mg. Subjects were housed from approximately 12 hours prior to study drug administration and
until after the 24 hour post-dose activities in each study period. Subjects reported to the clinical
facility for the 36.00, 48.00 and 72.00 hour ambulatory activities in each study period.
During the housing period, subjects were dosed with either the Test product (T) or Reference
product (R) as per the randomization schedule.
In each study period, blood samples were collected at pre-dose (0.00 hour) (within 90 minutes
prior to dose administration) and post-dose at 0.08, 0.17, 0.33, 0.50, 0.67, 0.83, 1.0, 1.33, 1.67,
2.0, 2.33, 2.67, 3.0, 3.50, 4.0, 4.50, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0 and 72.0
hours in each study period.
Number of Subjects (Planned and Analysed):
No. of Subjects Planned: 28

Page 6 of 79

dossier
mg
Lisdexamfetamine
No. of Subjects Enrolled: 28 (01-28).
No. of Subjects Completed: 27 (01-07 and 09-28).
Dropout/Withdrawn Subjects: 01 (Subject No. 08) (Refer to Appendix 16.2.1 for a list of
dropout/withdrawn subjects).
Subjects Included for Bioanalysis: 28 (01-28).
Subjects Included for Pharmacokinetic Analysis:
Lisdexamfetamine: 28 (01-28).
Dextroamphetamine: 27* (01-26 and 28).
Subjects Included for Statistical Analysis:
Lisdexamfetamine: 27# (01-07 and 09-28).
Dextroamphetamine: 26*# (01-07, 09-26 and 28).
Subjects Included for Bioequivalence Evaluation:
Lisdexamfetamine: 27 (01-07 and 09-28).
Note:
*The plasma samples for subject no. 27 were analysed, presented, and not considered for
pharmacokinetic analysis and statistical analysis as per protocol sections 12.1 (Sample
Analysis), 14.3 (Pharmacokinetic Analysis) and 14.4 (Statistical Analysis) for
Dextroamphetamine, since subject no. 27 had a pre-dose plasma concentration value is greater
than 5% of Cmax.
#
The plasma samples for subject no. 08 were analysed, presented, and considered for
pharmacokinetic analysis and not considered for statistical analysis as per protocol sections
12.1 (Sample Analysis), 14.3 (Pharmacokinetic Analysis) and 14.4 (Statistical Analysis) for
Dextroamphetamine and Lisdexamfetamine, since subject no. 08 completed one study period,

Page 7 of 79

dossier
mg
Lisdexamfetamine
hence subject was excluded from the statistical analysis.
Refer to section 11.0 for individual subjects data analysis.
Diagnosis and Main Criteria for Inclusion:
Healthy, adult, human subjects 18 years of age and older with a body mass index (BMI)
ranging between 18.0 to 32.5 kg/m2 were selected according to the inclusion and exclusion
criteria. Subjects were assessed to be in healthy condition based on a pre-study medical
examination and clinical laboratory tests.
Test Product, Dose, Mode of Administration and Batch Number:
Test Product (T): Lisdexamfetamine Dimesylate Capsules 70 mg
Dose: 1 x 70 mg
Mode of Administration: Oral
Lot/Batch No.: N479068
Duration of Treatment:
Treatment Periods:
Period-I: 28APR19
Period-II: 05MAY19
Washout Period:
A washout period of 07 days was maintained between each treatment schedule.
Reference Product, Dose, Mode of Administration and Batch Number:
Reference Product (R): Vyvanse® (Lisdexamfetamine Dimesylate) Capsules 70 mg
Dose: 1 x 70 mg
Mode of Administration: Oral
Lot/Batch No.: 3172362

Page 8 of 79

dossier
mg
Lisdexamfetamine
Criteria for Evaluation
Pharmacokinetic:
Plasma Lisdexamfetamine and Dextroamphetamine determined from blood samples collected
at pre-dose (0.00 hour) and post-dose at 0.08, 0.17, 0.33, 0.50, 0.67, 0.83, 1.0, 1.33, 1.67, 2.0,
2.33, 2.67, 3.0, 3.50, 4.0, 4.50, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0 and 72.0
Note: The pre-dose (0.00 hour) blood sample was collected within 90 minutes prior to dosing
in each study period.
Calculation of pharmacokinetic parameters were done for Lisdexamfetamine and
Dextroamphetamine using drug concentration-time data by non-compartmental method with
Phoenix WinNonlin® Software, Version 8.0 (Certara USA, Inc.). Statistical comparison of the
pharmacokinetic parameters of the two formulations was carried out using General Linear
Model (PROC GLM) of SAS® Release 9.4 (SAS Institute Inc., USA) to assess the oral
bioequivalence of Lisdexamfetamine. Descriptive statistics was computed and reported for
primary and secondary pharmacokinetic parameters for Lisdexamfetamine and
Dextroamphetamine.
All subjects who were dosed and did not withdraw consent from the study were included in
pharmacokinetic analyses. The statistical analysis population included all subjects with
sufficient plasma drug concentrations to adequately characterize Cmax and the AUC parameters.
No concentration estimates were provided for missing sample values. Any sample with a
missing value was treated as if the sample had not been collected. All plasma concentrations
below the lower limit of quantitation (BLQ) for the assay were treated as “0” in the
pharmacokinetic analyses and summary statistics. Any subject with a pre-dose value greater
than 5% of Cmax was dropped from pharmacokinetic and statistical analysis.
Primary pharmacokinetic parameters of Cmax, AUC0-t, and AUC0-, and secondary
pharmacokinetic parameters of AUC%Extrapolation, Tmax, Kel, and T½, for Lisdexamfetamine and
Dextroamphetamine were calculated for the test and reference products for each subject in each

Page 9 of 79

dossier
mg
Lisdexamfetamine
period.
Safety Evaluations:
Detailed medical examination including medical history, physical examination, vital signs
(blood pressure, pulse rate and temperature), clinical laboratory tests, urine pregnancy test (for
females), FSH test, and 12-lead ECG were carried out at the time of screening to exclude any
clinically significant medical condition that may interfere or was likely to interfere with the
pharmacokinetics of the drug. Safety assessments were carried out at the time of check-in and
throughout the study.
Urine drug screen and alcohol breath analysis were carried out at the time of screening and
each study period check-in.
Urine pregnancy test (for all females) was performed at the time of screening, each study
period check-in, and at the end of the study.
In each study period, vital signs monitoring (blood pressure, pulse rate and temperature) was
collected in a sitting position prior to dosing. Vital signs (blood pressure and pulse rate) were
collected at 2.00, 12.00 and 24.00 hours after each dose and at ambulatory visits (36.00, 48.00,
and 72.00 hours post-dose). All in-house and ambulatory vitals were collected within a window
period of ± 30 minutes to the scheduled time (for deviations, refer to Appendix 16.2.2.2),
except pre-dose vitals. Pre-dose vitals were collected within 90 minutes prior to dosing in each
study period.
Adverse event monitoring (subject well-being questionnaire) was done at pre-dose, at 2.00,
12.00 and 24.00 hours post-dose, and at ambulatory visits (36.00, 48.00, and 72.00 hours post-
dose). All in-house adverse event monitoring (subject well-being questionnaire) was collected
within a window period of ± 30 minutes to the scheduled time (for deviations, refer to
Appendix 16.2.2.2), except pre-dose SWBQ. Pre-dose SWBQ was collected within 90 minutes
prior to dosing in each study period.

Page 10 of 79

dossier
mg
Lisdexamfetamine
Statistical Methods:
Pharmacokinetic
Summary statistics, analysis of variance (ANOVA), 90% confidence intervals, geometric
means and ratio of means (ratio analysis), intra-subject variability, and power were calculated
for pharmacokinetic data of Lisdexamfetamine and Dextroamphetamine.
ANOVA was computed for Untransformed and Ln-transformed pharmacokinetic parameters of
Cmax, AUC0-t and AUC0- for Lisdexamfetamine and Dextroamphetamine.
Individual subject ratio analysis was computed for Untransformed pharmacokinetic parameters
of Cmax, AUC0-t and AUC0- for Lisdexamfetamine and Dextroamphetamine.
All statistical analyses for Lisdexamfetamine and Dextroamphetamine were performed using
PROC GLM Model of SAS® Release 9.4 (SAS Institute Inc., USA).
Safety:
Adverse events (AEs) were collected and tabulated for all subjects who received at least one
dose of Test product (T) or Reference product (R). No formal statistical analyses of safety data
were performed.
Summary-Conclusions
Pharmacokinetics Results:
A summary of results for statistical evaluations comparing Lisdexamfetamine Dimesylate
Capsules 70 mg of Test product (T) to Vyvanse® (Lisdexamfetamine Dimesylate) Capsules
70 mg of Reference product (R) is provided below.

Page 11 of 79

dossier
mg
Lisdexamfetamine
Lisdexamfetamine:
Ln-transformed Data
(N = 27*)
Parameter Geometric Mean Intra-
(T/R) 90% Confidence Power
Subject CV
Test (T) Reference (R) Ratio % Interval (%)
(%)
Cmax
40.2529 42.8597 93.92 86.67-101.78 17.4 100
(ng/mL)
AUC0-t
48.2379 50.1601 96.17 89.16-103.72 16.4 100
(hr. ng/mL)
AUC0-
48.8294 50.7590 96.20 89.31-103.62 16.1 100
(hr. ng/mL)
*Subject no. 08 completed one study period, hence subject was excluded from the
statistical analysis.
Dextroamphetamine:
Ln-transformed Data
(N = 26#)
Subject CV
(%)
Cmax
(ng/mL) 67.3195 66.3431 101.47 98.94-104.07 5.3 100
AUC0-t
(hr. ng/mL) 1123.2433 1083.5338 103.66 99.42-108.09 8.8 100
AUC0-
(hr. ng/mL) 1155.8341 1109.4460 104.18 99.86-108.69 8.8 100
#
Subject no. 08 completed one study period, hence subject was excluded from the
statistical analysis. Subject no. 27 had a pre-dose plasma concentration value is greater
than 5% of Cmax, hence subject was excluded from the statistical analysis.

Page 12 of 79

dossier
mg
Lisdexamfetamine
Note: For active metabolite, Dextroamphetamine, the above data was provided as supportive
evidence of the comparable therapeutic outcome, but was not included in the bioequivalence.
Safety Results:
 All the subjects’ vital signs were within normal range or considered not clinically significant
by the Investigator.
 All subjects were in normal healthy status at the time of subject well-being questionnaire
other than the reported adverse events listed.
 Over all, twelve (12) adverse events were reported in five (05) subjects in entire duration of
the study.
 Over all, seven (07) adverse events were reported in four (04) subjects in period-I.
 Subject no. 03 had headache which was considered possible in relation to treatment (T).
 Subject no. 06 had hyperhidrosis which was considered possible in relation to treatment
(R).
 Subject no. 08 had hyperhidrosis which was considered possible in relation to treatment
(T).
 Subject no. 08 had thirst which was considered unlikely in relation to treatment (T).
 Subject no. 17 had headache, dry mouth and dizziness which were considered possible in
relation to treatment (T).
 Over all, one (01) adverse event was reported in one (01) subject in prior to period-II
dosing.
 Subject no. 23 had injection site joint pain which was considered unlikely in relation to
treatment (R).
 Over all, four (04) adverse events were reported in three (03) subjects in period-II.
 Subject no. 03 had headache which was considered possible in relation to treatment (R).

Page 13 of 79

dossier
mg
Lisdexamfetamine
 Subject no. 17 had dizziness which was considered possible in relation to treatment (R).
 Subject no. 17 had headache which was considered unlikely in relation to treatment (R).
 Subject no. 23 had mood altered which was considered possible in relation to treatment
(T).
 No adverse events were reported in post-study lab investigations.
 All reported adverse events were mild in severity.
 All adverse events were resolved completely on follow-up.
 All subjects were found to be in normal healthy status at the time of post-study examination.
Serious/Significant Adverse Events: No serious adverse events were reported during the
study duration.
Deaths: No deaths were reported during the entire duration of the study.
Conclusion
Safety:
No serious adverse events (SAEs) were reported.
Overall, twelve (12) adverse events were reported in five (05) subjects over the course of the
study. All reported adverse events were mild in severity.
Five (05) AEs (headache, n = 2; hyperhidrosis, n = 1; dizziness, n = 1; injection site joint pain,
n = 1) occurred following oral administration of Reference product (R) of Vyvanse®
(Lisdexamfetamine Dimesylate) Capsules 70 mg. All reported adverse events were resolved
completely on follow-up.
Seven (07) AEs (headache, n = 2; hyperhidrosis, n = 1; thirst, n = 1; dizziness, n = 1; dry
mouth, n = 1; mood altered, n = 1) occurred following oral administration of Test product (T)
of Lisdexamfetamine Dimesylate Capsules 70 mg. All reported adverse events were resolved
completely on follow-up.

Page 14 of 79

dossier
mg
Lisdexamfetamine
There were no clinically significant findings of all subjects who participated in the post-study
safety assesments. Thus, the test product and reference product were comparable in safety
profile.
Overall, Lisdexamfetamine Dimesylate Capsules 70 mg was well tolerated as a single oral dose
when administered under fasting conditions.
Pharmacokinetics Conclusion:
Lisdexamfetamine:
The 90% confidence interval for geometric least squares mean ratios of Ln-transformed data of
Cmax, AUC0-t and AUC0- of Lisdexamfetamine were calculated:
Range of Ln-transformed 90% CI
Parameter Lisdexamfetamine
T Vs R
Cmax 86.67-101.78
AUC0-t 89.16-103.72
AUC0- 89.31-103.62
Based on these results, Lisdexamfetamine Dimesylate Capsules 70 mg (Test product) of

Norwich Pharmaceuticals, Inc. is bioequivalent with that of Vyvanse® (Lisdexamfetamine
Dimesylate) Capsules 70 mg (Reference product) of Shire US Inc., 300 Shire Way, Lexington,
MA 02421 when administered under fasting conditions.
Overall, Lisdexamfetamine Dimesylate Capsules 70 mg was well tolerated as a single oral dose
when administered under fasting conditions.
Date of the Report: 11JUL19

Page 15 of 79
3.0 TABLE OF CONTENTS FOR THE INDIVIDUAL CLINICAL STUDY REPORT

1.0 TITLE PAGE ........................................................................................................... 1
1.1 SIGNATURE PAGE ..................................................................................................................................3
2.0 SYNOPSIS ................................................................................................................ 4
3.0 TABLE OF CONTENTS FOR THE INDIVIDUAL CLINICAL STUDY
REPORT ................................................................................................................. 15
3.1 LIST OF TABLES ................................................................................................. 18
3.2 LIST OF FIGURES ............................................................................................... 19
4.0 LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ....................... 20
5.0 ETHICS .................................................................................................................. 23
5.1 INSTITUTIONAL REVIEW BOARD (IRB) ............................................................................................... 23
5.2 ETHICAL CONDUCT OF THE STUDY...................................................................................................... 23
5.3 SUBJECT INFORMATION AND CONSENT ............................................................................................... 23
6.0 INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ......... 25
7.0 INTRODUCTION.................................................................................................. 26
8.0 STUDY OBJECTIVES.......................................................................................... 28
9.0 INVESTIGATIONAL PLAN ............................................................................... 29
9.1 OVERALL STUDY DESIGN AND PLAN-DESCRIPTION ............................................................................ 29
9.2 DISCUSSION OF STUDY DESIGN, INCLUDING THE CHOICE OF CONTROL GROUPS ................................ 31
9.3 SELECTION OF STUDY POPULATION .................................................................................................... 32
9.3.1 Inclusion Criteria ............................................................................................................................... 32
9.3.2 Exclusion Criteria............................................................................................................................... 33
9.3.3 Removal of Subject from Therapy or Assessment ............................................................................... 35
9.4 TREATMENTS ...................................................................................................................................... 35
9.4.1 Treatments Administered .................................................................................................................... 35
9.4.2 Identity of Investigational Product(s) ................................................................................................. 36
9.4.3 Method of Assigning Subjects to Treatment Groups ........................................................................... 37
9.4.4 Selection of Doses in the Study ........................................................................................................... 37
9.4.5 Selection and Timing of Dose for Each Subject.................................................................................. 37
9.4.6 Blinding .............................................................................................................................................. 40
9.4.7 Prior and Concomitant Therapy ......................................................................................................... 40
9.4.8 Treatment Compliance ....................................................................................................................... 40
9.5 PHARMACOKINETIC AND SAFETY VARIABLES ..................................................................................... 41
9.5.1 Pharmacokinetic and Safety Measurements Assessed and Flow Chart .............................................. 41
9.5.2 Appropriateness of Measurements...................................................................................................... 43
9.5.3 Pharmacokinetic Variable(s) .............................................................................................................. 44
9.5.4 Drug Concentration Measurements.................................................................................................... 45
9.6 DATA QUALITY ASSURANCE ............................................................................................................... 46

Page 16 of 79
9.7 STATISTICAL METHODS PLANNED IN THE PROTOCOL AND DETERMINATION OF SAMPLE SIZE............ 47
9.7.1 Statistical and Analytical Plans .......................................................................................................... 47
9.7.2 Determination of Sample Size ............................................................................................................. 48
9.8 CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSIS ................................................... 49
10.0 STUDY SUBJECTS ............................................................................................... 49
10.1 DISPOSITION OF SUBJECTS................................................................................................................... 49
10.2 PROTOCOL DEVIATIONS ...................................................................................................................... 50
11.0 EFFICACY EVALUATION ................................................................................. 50
11.1 DATA SETS ANALYSED ....................................................................................................................... 50
11.2 DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS.................................................................. 51
11.3 MEASUREMENTS OF TREATMENT COMPLIANCE .................................................................................. 52
11.4 PHARMACOKINETIC RESULTS AND TABULATIONS OF INDIVIDUAL SUBJECT DATA ............................. 53
11.4.1 Analyses of Pharmacokinetics ............................................................................................................ 53
11.4.2 Statistical / Analytical Issues .............................................................................................................. 58
11.4.2.1 Adjustments for Covariates ........................................................................................................ 58
11.4.2.2 Handling of Dropouts or Missing Data...................................................................................... 59
11.4.2.3 Interim Analysis and Data Monitoring....................................................................................... 59
11.4.2.4 Multicentre Studies ..................................................................................................................... 59
11.4.2.5 Multiple Comparisons / Multiplicity .......................................................................................... 59
11.4.2.6 Use of an “Efficacy Subset” of Subjects .................................................................................... 59
11.4.2.7 Active-Control Studies Intended to Show Equivalence .............................................................. 59
11.4.2.8 Examination of Subgroups ......................................................................................................... 59
11.4.3 Tabulation of Individual Response Data ............................................................................................ 60
11.4.4 Drug Dose, Drug Concentration and Relationships to Response....................................................... 60
11.4.5 Drug-Drug and Drug-Disease Interactions ....................................................................................... 60
11.4.6 By-Subject Displays ............................................................................................................................ 60
11.4.7 Pharmacokinetic Conclusions ............................................................................................................ 60
12.0 SAFETY EVALUATION ...................................................................................... 61
12.1 EXTENT OF EXPOSURE......................................................................................................................... 61
12.2 ADVERSE EVENTS (AES) ..................................................................................................................... 61
12.2.1 Brief Summary of Adverse Events ....................................................................................................... 61
12.2.2 Display of Adverse Events .................................................................................................................. 63
12.2.3 Analysis of Adverse Events ................................................................................................................. 67
12.2.4 Listing of Adverse Events by Subjects................................................................................................. 67
12.3 DEATHS, OTHER SERIOUS ADVERSE EVENTS AND OTHER SIGNIFICANT ADVERSE EVENTS ................ 67
12.3.1 LISTING OF DEATHS, OTHER SERIOUS ADVERSE EVENTS AND OTHER SIGNIFICANT ADVERSE EVENTS
............................................................................................................................................................ 67
12.3.1.1 Deaths ........................................................................................................................................ 67
12.3.1.2 Other Serious Adverse Events .................................................................................................... 67
12.3.1.3 Other Significant Adverse Events ............................................................................................... 67
Page 17 of 79
12.3.2 Narratives of Deaths, Other Serious Adverse Events and Certain Other Significant Adverse Events68
12.3.3 Analysis and Discussion of Deaths, Other Serious Adverse Events and Other Significant Adverse
Events ................................................................................................................................................. 68
12.4 CLINICAL LABORATORY EVALUATION ................................................................................................ 68
12.4.1 Listing of Individual Laboratory Measurements by Subject and Each Abnormal Laboratory Values
............................................................................................................................................................ 68
12.4.2 Evaluation of Each Laboratory Parameter ........................................................................................ 68
12.4.2.1 Laboratory Values Over Time .................................................................................................... 68
12.4.2.2 Individual Subject Changes ........................................................................................................ 68
12.4.2.3 Individual Clinically Significant Abnormalities ......................................................................... 68
12.5 VITAL SIGNS, PHYSICAL FINDINGS AND OTHER OBSERVATIONS RELATED TO SAFETY ...................... 69
12.6 SAFETY CONCLUSIONS ........................................................................................................................ 69
13.0 DISCUSSION AND OVERALL CONCLUSIONS ............................................ 70
14.0 TABLES, FIGURES AND GRAPHS REFERRED TO BUT NOT INCLUDED
IN THE TEXT........................................................................................................ 71
14.1 DEMOGRAPHIC DATA .......................................................................................................................... 71
14.2 EFFICACY DATA .................................................................................................................................. 72
14.3 SAFETY DATA ..................................................................................................................................... 75
14.3.1 Displays of Adverse Events ................................................................................................................. 75
14.3.2 Listings of Deaths, Other Serious and Certain Other Significant Adverse Events ............................. 75
14.3.3 Narratives of Deaths, Other Serious and Certain Other Significant Adverse Events ......................... 75
14.3.4 Abnormal Laboratory Value Listings ................................................................................................. 75
15.0 REFERENCE LIST ............................................................................................... 76
16.0 APPENDICES ........................................................................................................ 78

Page 18 of 79
3.1 List of Tables
Table 1 Abbreviations and Specialist Terms .............................................................................. 20
Table 2 Schedule of Events ........................................................................................................ 29
Table 3 Identification of Investigational Products...................................................................... 36
Table 4 Summary of Demographic Characteristics1 of Subjects at Enrollment and Completion

.................................................................................................................................................... 51
Table 5 Treatment Means for Lisdexamfetamine Pharmacokinetic Parameters ........................ 53
Table 6 Treatment Means for Dextroamphetamine Pharmacokinetic Parameters ..................... 54
Table 7 Summary of Treatment-Emergent Adverse Events ....................................................... 63
Table 8 Statistical Comparisons of Pharmacokinetic Parameters for Test Product Vs. Reference
Product........................................................................................................................................ 72

Page 19 of 79
3.2 List of Figures
Figure 1 Linear Plot of Mean Plasma Concentrations Vs Time of Lisdexamfetamine .............. 56
Figure 2 Semi - log Plot of Mean Plasma Concentrations Vs Time of Lisdexamfetamine ........ 56
Figure 3 Linear Plot of Mean Plasma Concentrations Vs Time of Dextroamphetamine ........... 57
Figure 4 Semi - log Plot of Mean Plasma Concentrations Vs Time of Dextroamphetamine ..... 57

Page 20 of 79
4.0 LIST OF ABBREVIATIONS AND DEFINITION OF TERMS

The following abbreviations and specialist terms listed in Table 1 were used in the
clinical study report.
Table 1 Abbreviations and Specialist Terms

ADHD : Attention Deficit Hyperactivity Disorder
AE : Adverse Event
ANDA : Abbreviated New Drug Application
ANOVA : Analysis of Variance
AUC : Area Under the plasma concentration versus time Curve
The area under the plasma concentration versus time curve,
AUC0-t : from time 0 to the last measurable concentration, as
calculated by the linear trapezoidal method.
The area under the plasma concentration versus time curve
from time 0 to time infinity. AUC0- is calculated as the sum
AUC0- :
of the AUC0-t plus the ratio of the last measurable plasma
concentration (Ct) to the elimination rate constant Kel.
AUC%Extrapolation : Extrapolated AUC percentage of total AUC.
BA : Bioavailability
BE : Bioequivalence
BED : Binge Eating Disorder
BLQ : Below the Lower Limit of Quantitation
BMI : Body Mass Index
°C : Degree Celsius
CFR : Code of Federal Regulations
CI : Confidence Interval
Cmax Maximum measured plasma concentration over the time
:
span specified.
CNS : Central Nervous System
COA : Certificate of Analysis
CRF : Case Report Form
Ct : Last Measurable Concentration
CV : Coefficient of Variation/Curriculum vitae
CYP2D6 : Cytochrome P450 2D6
DOPA : 3,4-Dihydroxyphenylalanine
ECG : Electrocardiogram

Page 21 of 79
e.g. : for example

FDA : Food and Drug Administration
FSH : Follicle-Stimulating Hormone
g : Gram
GCP : Good Clinical Practice
GLM : General Linear Model
h/hr/hr./hrs : Hours
HBsAg : Hepatitis B Surface Antigen
HCl : Hydrochloride
HCV : Hepatitis C Virus
HIV : Human Immunodeficiency Virus
i.e. : that is
ICF : Informed Consent Form
ICH : International Conference on Harmonisation
Inc. : Incorporated
IND : Investigational New Drug
IRB : Institutional Review Board
IUD : Intrauterine Device
Apparent first order elimination rate constant calculated
from a semi-log plot of plasma concentration versus time
Kel : point. The parameter will be calculated by linear square
regression analysis using the last 3 (or more) non-zero
plasma concentrations.
kg : Kilogram
kg/m2 : Kilogram per meter square
K2EDTA : Di-potassium Ethylenediaminetetraacetic Acid
L : Liter
LC-MS/MS : Liquid Chromatography-Tandem Mass Spectrometry
LLC : Limited Liability Company
m : Meter
MAOI : Monoamine Oxidase Inhibitor
MDMA : 3,4-methylenedioxy-N-methylamphetamine
MedDRA : Medical Dictionary for Regulatory Activities
mg : Milligram
mL : Milliliter
N : Number of subjects

Page 22 of 79
NA : Not Applicable
NCS : Not Clinically Significant
ng : Nanogram
ng/mL : Nanogram per Millilitre
NIA : National Institute on Aging
No./no. : Number
p-value : Probability Value
PCP : Phencyclidine
PK : Pharmacokinetics
PROC : Procedure
QC : Quality Control
R : Reference Product
RPM : Revolutions Per Minute
S : Subject
SAE : Serious Adverse Event
SAS : Statistical Analysis System
SD : Standard Deviation
SNRIs : Serotonin Norepinephrine Reuptake Inhibitors
SOP : Standard Operating Procedure
SSRIs : Selective Serotonin Reuptake Inhibitors
SWBQ : Subject Well-Being Questionnaire
T : Test Product
T½ : The elimination or terminal half-life.
THC : Tetrahydrocannabinol
Tmax : Time of the maximum measured plasma concentration.
US : United States
USA : United States of America
USFDA : United States Food and Drug Administration
Vs/vs : Versus
WHO-UMC : World Health Organization – Uppsala Monitoring Centre
WMA : World Medical Association

Page 23 of 79
5.0 ETHICS
5.1 Institutional Review Board (IRB)
Study protocol (Protocol No.: A17.0566, Version No.: 01, Dated: 12MAR19),
Informed Consent Form (English, Version 01) and other supporting documents for the
study drug were submitted for review to IntegReview Institutional Review Board on
12MAR19.
Written approval for Study protocol (Protocol No.: A17.0566, Version No.: 01, Dated:
12MAR19), Informed Consent Form (English, Version 01) and other supporting
documents for the study drug was obtained from IntegReview Institutional Review
Board on 19MAR19.
The study was started as per the protocol bearing Study No.: A17.0566, Version No.:
02, Dated: 12MAR19, which was approved by IntegReview Institutional Review
Board on 19MAR19.
During the conduct of the study, IntegReview Institutional Review Board was apprised
of all the events reported in the study.
Refer to Appendix 16.1.1 for protocol and protocol amendments (as applicable), and
Appendix 16.1.3 for IntegReview IRB approval.
5.2 Ethical Conduct of the Study

This study was carried in compliance with the protocol and good clinical practices as
per the following guidelines:
 The Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil,
October 2013).
 Integrated Addendum to ICH-E6 (R1) Guidance for Good Clinical Practice March
2018.
 FDA Bioanalytical Guidance.
 Guidance for Industry – Bioequivalence Studies with Pharmacokinetic Endpoints
for Drugs Submitted Under an ANDA (USFDA, December 2013).
5.3 Subject Information and Consent

All subjects who agreed to participate in the study were required to provide the
investigators with properly documented and fully executed (signed by all parties)
informed consent prior to the initiation of any study-specific activities.
Delegated staff were responsible for preparing the written informed consent documents

Page 24 of 79
for this study. The documents incorporated the required elements for informed consent,
including the possible treatment risks. The study-specific consent form embodied
elements of informed consent and necessary documentation as required by 21 CFR 50.
The study-specific informed consent form was reviewed and approved by the
IntegReview Institutional Review Board before use.
At the screening visit, all subjects reviewed the Informed Consent form approved by the
IntegReview Institutional Review Board. All subjects were provided information about
the study through the study information consent form. The investigator or delegated
study staff members provided the subjects with an explanation of the nature of the
study, including the purpose, procedures, expected duration, and potential risks.
Prospective participants were informed of their right to withdraw from the study at any
time without prejudice. At the screening visit, study procedures and potential risks, as
described in the study-specific ICF, were reviewed with each subject with the
opportunity to ask questions and have them answered. If consent was obtained, the
subject signed and dated the informed consent form during period-I check-in. The
original consent form was kept in the subject’s records, and a copy of the signed and
dated consent form was provided to the subject.
Please refer to the subject’s individual case report forms for the dates that ICF Version
01 was signed by each individual subject.
A sample of the informed consent form is provided in Appendix 16.1.3.

Page 25 of 79
6.0 INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE
Designation Name of the Individual Responsibility
Planning and scheduling of projects and delegation of

investigators of various phases i.e. clinical, statistical.
Obtain informed consent, adverse event review,
Peter C. Boldingh, Pharm.D., regulatory binder maintenance, CRF entry/corrections,
Principal Investigator
R.Ph. study activity conduct/ supervision, IRB
communication, SAE reporting and investigational
product handling. Dr. Boldingh is also the authorized
signatory for the final report.
Adverse event review, study activity
Patrick A. Luger, M.D. conduct/supervision, physical examination/clinical lab
and ECG review.
Obtain informed consent, regulatory binder
maintenance, CRF entry/corrections, study activity
Sub-Investigator Brent Gillund, MA, CCRC
conduct/supervision, IRB communication and SAE
reporting.
Obtain informed consent, regulatory binder
Harry Moskowitz, B.A. maintenance, CRF entry/corrections, study activity
conduct/supervision, and SAE reporting.
Study activity conduct/supervision and investigational
Pharmacist Lisa Odegaard, Pharm.D., R.Ph.
product handling.
Check that documentation and record-keeping
Sr. Manager, Quality
Amy Karels, BS, CCRC requirements are met internally to support regulatory
Assurance
submissions.
Plan and monitor the work on method development,
validation, and study sample analysis using
Bioanalytical Ardeshir Khadang,
HPLC/LC/MS/MS techniques as per the principles of
Investigator BS Analytical Chemistry
GLP and SOPs of AXIS Clinicals as well as approved
protocols.
Provide information for literature survey on
pharmacokinetic studies conducted previously on the
Pharmacokinetic
Vidya Sagar Papani, M. Pharm drug, review of protocol and report, and perform
Investigator
pharmacokinetic analysis with Phoenix WinNonlin®
Software, Version 8.0 (Certara USA, Inc.).
Statistical Preparation of randomization schedule and perform
Rakesh.P, M.Sc. Statistics
Investigator statistical analysis with SAS® Version 9.4.
The list of investigators with their affiliation and qualification is provided in Appendix
16.1.4.

Page 26 of 79
7.0 INTRODUCTION
Background Information
The present study is to compare the rate and extent of absorption of Lisdexamfetamine
Dimesylate Capsules 70 mg (Test) of Norwich Pharmaceuticals, Inc. with Vyvanse®
(Lisdexamfetamine Dimesylate) Capsules 70 mg (Reference) of Shire US Inc. when
given as a single oral dose to healthy, adult, human subjects under fasting conditions.
Indications and Usage
Vyvanse® is indicated for the treatment of:
 Attention Deficit Hyperactivity Disorder (ADHD)
 Moderate to Severe Binge Eating Disorder (BED) in adults.
Limitation of Use:
Vyvanse® is not indicated or recommended for weight loss. Use of other
sympathomimetic drugs for weight loss has been associated with serious cardiovascular
adverse events. The safety and effectiveness of Vyvanse® for the treatment of obesity
have not been established:
Pharmacokinetics
Pharmacokinetic studies after oral administration of Lisdexamfetamine dimesylate have
been conducted in healthy adult (capsule and chewable tablet formulations) and
pediatric (6 to 12 years) patients with ADHD (capsule formulation). After single dose
administration of Lisdexamfetamine dimesylate, pharmacokinetics of
dextroamphetamine was found to be linear between 30 mg and 70 mg in a pediatric
study and between 50 mg and 250 mg in an adult study. Dextroamphetamine
pharmacokinetic parameters following administration of Lisdexamfetamine dimesylate
in adults exhibited low inter-subject (<25%) and intra-subject (<8%) variability.
There is no accumulation of Lisdexamfetamine and dextroamphetamine at steady state
in healthy adults.
Safety and efficacy have not been studied above the maximum recommended dose of
70 mg.
Absorption:
Capsule formulation: Following single-dose oral administration of Vyvanse® capsule
(30 mg, 50 mg, or 70 mg) in patient’s ages 6 to 12 years with ADHD under fasted
conditions, Tmax of Lisdexamfetamine and dextroamphetamine was reached at
approximately 1 hour and 3.5 hour post dose, respectively. Weight/Dose normalized
AUC and Cmax values were the same in pediatric patient’s ages 6 to 12 years as the

Page 27 of 79
adults following single doses of 30 mg to 70 mg Vyvanse® capsule.

Food effect on capsule formulation:
Neither food (a high fat meal or yogurt) nor orange juice affects the observed AUC and
Cmax of dextroamphetamine in healthy adults after single-dose oral administration of 70
mg of Vyvanse® capsules. Food prolongs Tmax by approximately 1 hour (from 3.8 hour
at fasted state to 4.7 hour after a high fat meal or to 4.2 hour with yogurt). After an 8-
hour fast, the AUC for dextroamphetamine following oral administration of
Lisdexamfetamine dimesylate in solution and as intact capsules were equivalent.
Chewable Tablet formulation: After a single dose administration of 60 mg Vyvanse®
chewable tablet in healthy subjects under fasted conditions, Tmax of Lisdexamfetamine
and dextroamphetamine was reached at approximately 1 hour and 4.4 hour post dose,
respectively. Compared to 60 mg Vyvanse® capsule, exposure (Cmax and AUC) to
Lisdexamfetamine was about 15% lower. The exposure (Cmax and AUCinf) of
dextroamphetamine is similar between Vyvanse® chewable tablet and Vyvanse®
capsule.
Food effect on tablet formulation:
Administration of 60 mg Vyvanse® chewable tablet with food (a high-fat meal)
decreases the exposure (Cmax and AUCinf) of dextroamphetamine by about 5% to 7%,
and prolongs mean Tmax by approximately 1 hour (from 3.9 hrs at fasted state to 4.9
hours).
Elimination:
Plasma concentrations of unconverted Lisdexamfetamine are low and transient,
generally becoming non-quantifiable by 8 hours after administration. The plasma
elimination half-life of Lisdexamfetamine typically averaged less than one hour in
studies of Lisdexamfetamine dimesylate in volunteers. The mean plasma elimination
half-life of dextroamphetamine was about 12 hours after oral administration of
Lisdexamfetamine Dimesylate.
Metabolism:
Lisdexamfetamine is converted to dextroamphetamine and l-lysine primarily in blood
due to the hydrolytic activity of red blood cells after oral administration of
Lisdexamfetamine dimesylate.
In vitro data demonstrated that red blood cells have a high capacity for metabolism of
Lisdexamfetamine; substantial hydrolysis occurred even at low hematocrit levels (33%
of normal). Lisdexamfetamine is not metabolized by cytochrome P450 enzymes.

Page 28 of 79
Excretion:
Following oral administration of a 70 mg dose of radiolabeled Lisdexamfetamine
dimesylate to 6 healthy subjects, approximately 96% of the oral dose radioactivity was
recovered in the urine and only 0.3% recovered in the feces over a period of 120 hours.
Of the radioactivity recovered in the urine, 42% of the dose was related to
amphetamine, 25% to hippuric acid, and 2% to intact Lisdexamfetamine.
Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections.
 Known hypersensitivity to amphetamine products or other ingredients of
Vyvanse®.
 Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase
Inhibitors.
 Drug Dependence.
 Serious Cardiovascular Reactions.
 Blood Pressure and Heart Rate Increases.
 Psychiatric Adverse Reactions.
 Suppression of Growth.
 Peripheral Vasculopathy, including Raynaud’s phenomenon.
 Serotonin Syndrome.
8.0 STUDY OBJECTIVES

Primary Objective:
To compare the rate and extent of absorption of Lisdexamfetamine Dimesylate
Capsules 70 mg (Test) of Norwich Pharmaceuticals, Inc. with Vyvanse®
(Lisdexamfetamine Dimesylate) Capsules 70 mg (Reference) of Shire US Inc., under
fasting conditions.
Secondary Objective:
To monitor for adverse events and optimize subject safety.

Page 29 of 79
9.0 INVESTIGATIONAL PLAN

9.1 Overall Study Design and Plan-Description
The schedule of events is presented in Table 2.
Table 2 Schedule of Events
Activity/Event Period-I Period-II
04MAY19
05MAY19
06MAY19
29APR19
27APR19
28APR19
Date
Screening 08APR19 – 24APR19

Study Informed Consent 27APR19
Drug Dispensing 26APR19 - - 03MAY19 - -
Urine Sample for Drugs of Abuse  - -  - -
Alcohol Breath Analysis  - -  - -
Urine Pregnancy Test (for females)  - -  - 
Check-in  - -  - -
Drug Administration -  - -  -
Blood Sample Collection -   -  
Vital Signs -   -  
SWBQ -   -  
Snack   -   -
Lunch -  - -  -
Dinner -  - -  -
Check-out - -  - - 
Ambulatory Visits 29APR19 (36.00 hr) 06MAY19 (36.00 hr)
(Vital Signs, SWBQ and Blood 30APR19 (48.00 hr) 07MAY19 (48.00 hr)
Sample Collection) 01MAY19 (72.00 hr) 08MAY19 (72.00 hr)
Post-study Safety Assessments
(Vital Signs, Hematology,
All subjects on 08MAY19
Chemistry, and Urine Pregnancy
Test (for females))
Plasma Samples Transferred from
Clinical Unit to Bioanalytical 08MAY19
Department
Methodology:
This was an open label, randomized, two-treatment, two-sequence, two-period,
cross-over, single-dose study investigating the bioequivalence of Lisdexamfetamine
Dimesylate Capsules 70 mg (Test) of Norwich Pharmaceuticals, Inc., with that of
Page 30 of 79
Vyvanse® (Lisdexamfetamine Dimesylate) Capsules 70 mg (Reference) of Shire US

Inc., 300 Shire Way, Lexington, MA 02421.
Healthy, adult, human subjects 18 years of age and older with a Body Mass Index
(BMI) ranging between 18.0 to 32.5 kg/m2 were selected according to the inclusion and
exclusion criteria. Subjects were assessed to be in healthy condition based on a pre-
study medical examination including medications, allergies, and health history; a
physical examination including vital signs (blood pressure, respiratory rate, pulse rate
and temperature); 12-lead ECG; demographic data including sex, date of birth, height,
weight, BMI, history of smoking, history of intake of abusive/recreational drugs,
history of alcohol consumption, history of blood donation, and history of participation
in a drug research study; and clinical laboratory tests [hematology, chemistry,
urinalysis, test for drugs of abuse, alcohol breath analysis, screening for infection
diseases (HIV 1 & 2, HBsAg and HCV), FSH test, and serum pregnancy test (for all
females)].
Drugs of abuse screen [Amphetamine, Barbiturates, Benzodiazepines, Cocaine
metabolites, Marijuana (THC), Methadone, MDMA (3,4-methylenedioxy-
methamphetamine [Ecstasy]), Opiates, Opioids, Phencyclidine (PCP)] and an alcohol
breath analysis were performed during screening and each period check-in; those with
negative results were eligible for the study. Urine pregnancy test (for all females) was
performed at screening, each study check-in, and at the end of the study (refer to
Appendix 16.2.8.1 for a listing of laboratory values by subject).
Subjects screened within 28 days prior to the scheduled dosing day of period-I and who
were found to fulfill the inclusion and exclusion criteria were enrolled in this study.
This study was initiated with twenty-eight (28) (01-28) healthy, adult, human subjects
and twenty-seven (27) (01-07 and 09-28) subjects completed the study. All subjects
checked into the clinical facility on the day prior to dosing. Check-in occurred at least
12 hours prior to dose administration for each study period.
On study Day 1, after an overnight fasting of at least 10.0 hours, each subject received a
single oral dose of Lisdexamfetamine Dimesylate 70 mg × 1 Capsules of either Test
product (T) or Reference product (R) with approximately 240 mL of drinking water at
room temperature as per the randomization schedule (refer to Appendix 16.1.7). A
washout period of 07 days was maintained between each treatment schedule.
In each study period, blood samples were collected at pre-dose (0.00 hour) (within 90
minutes prior to dose administration) and post-dose at 0.08, 0.17, 0.33, 0.50, 0.67, 0.83,
1.0, 1.33, 1.67, 2.0, 2.33, 2.67, 3.0, 3.50, 4.0, 4.50, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0,

Page 31 of 79
24.0, 36.0, 48.0 and 72.0 hours. Subjects were allowed to leave the clinical facility after
the 24.00 hour post-dose activities. Subjects returned to the clinical facility for the
36.00, 48.00 and 72.00 hour study activities.
For each subject who completed the study, the total number of blood draws was 56 (28
x 2, for two periods) and the total volume of blood withdrawn was 356 mL.
PROCESS BREAKDOWN TOTAL
Screening 12.5 mL 12.5 mL
Period-I 28 X 1 X 6 mL 168 mL
Period-II 28 X 1 X 6 mL 168 mL
Post-study 7.5 mL 7.5 mL
Total Blood Loss 356 mL
Dietary Plan:
Subjects were provided a snack at check-in (Day -1) of each study period. Subjects
maintained an overnight fasting for at least 10.0 hours in each study period before drug
administration and four hours thereafter. Post-dose meals on Day 1 (Dosing Day) were
provided at approximately 4.5, 10 and 13 hours during each study period.
Standard meals were provided by the caterer. During housing, the meal plans were kept
identical for all periods. Information on the standardized meal, quantity consumed and
time was documented.
Drinking water was not permitted one hour before dosing until two hours post-dose; at
other times drinking water was permitted ad libitum.
Post-dose meals were provided with a window period of ± 30 minutes to the scheduled
time.
Date Times / Meal Type Menu Item
27APR19 Soft Pretzel and Hot Cheese Sauce, Applesauce, Protein Bar,
8:00 PM / Snack
04MAY19 Water
Burger Sandwich, Garden Salad, Mini Cheesecakes, 2% Milk
12:30 PM / Lunch
and/or Water
28APR19
Tomato Basil Soup, Tater Tot Casserole, Garden Salad, Dinner
05MAY19 6:00 PM / Dinner
Roll, 2% Milk and/or Water
9:00 PM / Snack Turkey Cold Sandwich, Applesauce, Protein Bar, Water
9.2 Discussion of Study Design, Including the Choice of Control Groups

Norwich Pharmaceuticals, Inc. is seeking approval in the United States for
Lisdexamfetamine Dimesylate Capsules 70 mg of Norwich Pharmaceuticals, Inc., a

Page 32 of 79
generic version of Shire US Inc., 300 Shire Way, Lexington, MA 02421 of Vyvanse®
(Lisdexamfetamine Dimesylate) Capsules 70 mg for which demonstration of
bioequivalence is required.
Since this was an open-label study, the randomization code was available to clinical
staff for dosing, and to the statisticians and medical writers for report writing purposes.
The randomization scheme was computer generated by using SAS® software at AXIS
Clinicals LLC offshore office and subjects were randomized prior to drug
administration.
This study was designed based on the known pharmacokinetics of Lisdexamfetamine
and Dextroamphetamine and the generally accepted standards for the conduct of
bioavailability and bioequivalence studies under fed conditions. Due to the nature of the
study (i.e., bioequivalence study), no control group was utilized.
9.3 Selection of Study Population

Eligibility assessments were done before enrollment of the subject into the study.
Subjects were recruited from a database and/or general advertising and selected during
screening to meet all of the following inclusion and exclusion criteria.
9.3.1 Inclusion Criteria

Subjects who met the following criteria were considered for inclusion into this study:
1. Healthy, adult, human subjects 18 years of age and older, inclusive.
2. Body Mass Index (BMI) ranging between 18.0 to 32.5 kg/m2, inclusive (according
to the formula of BMI = weight (kg) / [height (m)2]).
3. No evidence of underlying disease during screening or at period-I check-in.
4. Screening clinical laboratory values are within normal limits or considered by the
physician or Principal Investigator to be of no clinical significance.
5. Absence of disease markers of HIV 1 & 2, and Hepatitis B & C virus.
6. Generally healthy as documented by the medical history, physical examination
(including but may not be limited to an evaluation of the cardiovascular,
gastrointestinal, respiratory, musculoskeletal and central nervous systems) and vital
sign assessments.
7. Generally healthy as documented by 12-lead electrocardiogram (ECG).
8. Any subject abnormalities/deviations from the acceptable range for medical history,
clinical laboratory values, ECG and vitals not considered clinically significant by
the medical or clinical investigator.

Page 33 of 79
9. Able to comply with study procedures, in the opinion of the Principal Investigator.
10. Willing to give written consent and adhere to all the requirements of this protocol.
11. Female subjects of childbearing potential:
 Non-pregnant and non-lactating females practicing a medically acceptable
form of birth control and willing to continue during the study.
 Medically acceptable forms of birth control from screening to until 28 days of
study completion include:
1. Abstinence
2. Hormonal contraceptives (for at least 1 month prior to screening)
3. Double barrier (e.g., diaphragm with spermicide; condom with
spermicide)
4. Intrauterine device (IUD) or
5. Surgically sterile (e.g., bilateral tubal ligation and bilateral oophorectomy).
12. Postmenopausal female subjects age ≥ 45 years:
 Amenorrhea for at least 1 year or
 Bilateral oophorectomy with or without a hysterectomy and an absence of
bleeding for at least 6 months or
 Total hysterectomy and an absence of bleeding for at least 3 months.
9.3.2 Exclusion Criteria

Subjects who met any of the following criteria were excluded from this study:
1. Institutionalized subjects.
2. Evidence of allergy or known hypersensitivity or idiosyncratic reaction to
Lisdexamfetamine.
3. Clinically significant history of alcoholism within twelve months of period-I dosing
as per Investigator discretion.
4. Clinically significant history of addiction, abuse and misuse of any drug as per
Investigator discretion.
5. Any major illness in the last three months or any significant ongoing chronic
medical illness.
6. Smoke (≥ 10 cigarettes /day or equivalent) or consume tobacco products (≥ 4 chews
of any form/day).
7. Presence or history of a clinically significant disorder involving the cardiovascular,
respiratory, renal, hepatic, dermatologic, musculoskeletal, gastrointestinal,
immunologic, hematologic, endocrine or neurologic system(s) or psychiatric
disease (as determined by the Medical Investigator).

Page 34 of 79
 The examination should specifically avoid subjects with a history of advanced

arteriosclerosis, Tourette’s syndrome, symptomatic cardiovascular disease,
moderate to severe hypertension, severe psychiatric disease, and seizures, as
determined by the Medical Investigator.
8. Participation in any clinical trial within 30 days prior to dosing.
9. History of difficulty swallowing.
10. Report of dehydration from diarrhea, vomiting, or any other reason within a period
of 48 hours prior to dosing.
11. History or complaints of frequent dizziness or light headedness (“frequent” defined
as incidence occurs more than once every week).
12. Any blood donation/excess blood loss within 30 days or plasma donation within
14 days prior to dosing.
13. History of difficult venipuncture
14. Existence of any surgical or medical condition which, in the judgment of
Investigator(s), might interfere with the absorption, distribution, metabolism or
elimination of the study drug or is likely to compromise the safety of the subject
15. Positive results for drugs of abuse or alcohol breathalyzer prior to dosing.
16. Ingestion of any hormonal medication except hormonal contraceptives at any time
within 14 days prior to dosing.
17. Using of monoamine oxidase inhibitors (MAOIs), (e.g., selegiline,
tranylcypromine, isocarboxazid, phenelzine, linezolid, and methylene blue) and
CNS stimulants (selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid,
methylene blue), selective serotonin reuptake inhibitors (SSRI) within 30 days
prior to check-in of period-I.
18. Using of gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic
acid HCl, and ascorbic acid) and coumarin anticoagulants, anticonvulsants (e.g.,
phenobarbital, phenytoin, primidone), dopamine agonists (including DOPA and
tricyclic antidepressants) as well as dopamine antagonists (antipsychotics, e.g.,
haloperidol), and tricyclic drugs (e.g., imipramine, clomipramine, desipramine)
within 30 days prior to check-in of period-I.
19. Using of proton pump inhibitors (omeprazole), antihistamines, antihypertensives,
chlorpromazine, ethosuximide, haloperidol, lithium carbonate, meperidine,
methenamine therapy, norepinephrine, phenobarbital, phenytoin, propoxyphene,
and veratrum alkaloids, within 30 days prior to check-in of period-I.
20. Using of any concomitant serotonergic agents serotonin norepinephrine reuptake
inhibitors (SNRIs) (triptans, tricyclic antidepressants, fentanyl, lithium, tramadol,
tryptophan, buspirone, and St. John’s Wort) or CYP2D6 inhibitors for 30 days prior
to check-in of period-I.
Page 35 of 79
21. Female subjects:

 Demonstrating a positive pregnancy test at screening or check-in.
 Who are currently breastfeeding.
 Use hormone replacement therapy within three months prior to dosing.
9.3.3 Removal of Subject from Therapy or Assessment

In accordance with the ICH-GCP guidelines, all the subjects had the right to withdraw
from the study at any time, regardless of their reasons. Over the course of the study, the
clinical investigators and/or sponsor can decide to withdraw/discontinue any subject
from the study in the case of unnecessary risk, adverse events, non-compliance, or any
of the following reasons during the course of the study.
 If the subject suffers from significant illness or adverse event.
 If the subject vomits within 8 hours (2 times median Tmax) after study drug
dosing in any period.
 If the subject is uncooperative, destructive or treats their study colleagues in a
rude, hurtful manner.
 If the subject voluntarily withdraws consent from the study.
 If the subject continuously misses sample around Cmax and then withdraws
from the study.
 If the subject is non-compliant.
Subjects withdrawn/dropout from study

Refer to Appendix 16.2.1 for a list of withdrawn/dropout subjects.
9.4 Treatments
9.4.1 Treatments Administered
The following treatments were administered under fasting conditions:
Vyvanse® (Lisdexamfetamine Dimesylate) Capsules 70
Reference Product (R) :
mg.
Manufactured for : Shire US Inc., 300 Shire Way, Lexington, MA 02421.
Test Product (T) : Lisdexamfetamine Dimesylate Capsules 70 mg.
Manufactured by : Norwich Pharmaceuticals, Inc., Norwich NY, 13815.
Name of Sponsor : Norwich Pharmaceuticals, Inc.

Page 36 of 79
Drug Administration:
After an overnight fasting of at least 10.0 hours, each subject received a single oral dose
of Lisdexamfetamine Dimesylate 70 mg × 1 Capsules Test product (T) or Reference
product (R) with approximately 240 mL of drinking water at room temperature as per
the randomization schedule by study personnel.
Subjects received the Test product (T) once and Reference product (R) once with the
following treatment sequence as per the randomization schedule:
Sequence Period-I Period-II
Sequence 1 R T
Sequence 2 T R
Investigational drug product (Test product and Reference product) was administered to
the subjects on 28APR19 for period-I and on 05MAY19 for period-II.
Dosing for the subjects started at 08:00 and completed at 08:13 for both study periods.
Drug administration was carried out in two (02) dosing stations in both study periods.
Refer to section 9.4.5 for the drug administration schedule for individual subjects.
9.4.2 Identity of Investigational Product(s)

Investigational products were shipped by the sponsor and received by the pharmacist
along with relevant shipment documents. The received investigational products were
verified for the sealed condition of packs and adequacy of label such as product name,
strength, manufacturer, manufacturing date, lot number or batch number, expiry
date/retest date, the certificate of analysis (COA), and storage conditions.
The investigational products are described below in Table 3.
Table 3 Identification of Investigational Products

Details Reference Product (R) Test Product (T)
Lisdexamfetamine Dimesylate Lisdexamfetamine Dimesylate
Generic Name
Capsules 70 mg Capsules 70 mg
Vyvanse® (Lisdexamfetamine
Trade Name NA
Dimesylate) Capsules 70 mg
Dosage Form Capsule Capsule
Manufactured by NA
Norwich NY, 13815
Shire US Inc.
Manufactured for NA
300 Shire Way

Page 37 of 79
Details Reference Product (R) Test Product (T)

Lexington, MA 02421
Dose 1 x 70 mg 1 x 70 mg
Lot/Batch No. 3172362 N479068
Manufacturing Date NA NA
Expiry Date 10/2021 FEB/2021 (Planned)
Hard shell, locking gelatin Hard shell, locking gelatin
capsules, orange cap and blue capsules, orange cap and blue
body. "S489" printed axially body, "ALV" printed axially
on the orange cap, "70 mg" on the orange cap, "568"
Characteristics
printed axially on the blue printed axially on the blue
body, all printing in black ink. body, all printing in grey ink.
Contents: White to off-white Contents: White to off-white
powder. powder.
Assay Value(s) 99.8% 98.9%
The difference in the assay values of Test product (T) and Reference product (R) is not
more than 5%.
9.4.3 Method of Assigning Subjects to Treatment Groups

The randomization schedule was generated on 23APR19 using SAS® software (Version
No. 9.4) at AXIS Clinicals LLC Offshore Office. The order of receiving either Test
product (T) or Reference product (R) for each subject during each study period was
determined according to the open-label randomization schedule provided by the
biostatistician. The randomization was balanced and the code was kept under controlled
access. Equal allocation of the subjects to each sequence was ensured. The
randomization schedule is presented in Appendix 16.1.7.
9.4.4 Selection of Doses in the Study

A single oral dose of 70 mg was given to achieve sufficient plasma concentration level
to characterize the pharmacokinetic profile. The subjects were given a single oral dose
Dextroamphetamine suspension (either Test product (T) or Reference product (R)) as
per the randomization schedule in each study period.
9.4.5 Selection and Timing of Dose for Each Subject

All the subjects maintained an overnight fasting state from at least 10.0 hours prior to
administration of investigational product and a minimum of four hours thereafter. On
Day 1 (Dosing Day), a single oral dose of the study drug (either Test product (T) or
Reference product (R)) was administered with approximately 240 mL of drinking water

Page 38 of 79
at room temperature. Study drug dosing was done on 28APR19 for period-I and on
05MAY19 for period-II.
Before administration of the study drug on dosing day, the Principal Investigator
checked each dispensed unit dose label against the randomization schedule for the
treatment to be administered. They also ensured that the subject number on the label
corresponded to the number allocated to each recipient in each study period.
Dosing was staggered at specific intervals between 08:00 and 08:13 in both study
periods.
The dose was administered in a staggered manner to maintain subsequent blood
collection schedule. The information regarding the schedule and actual time of dosing
for each subject for both study periods is given below.
Drug Administration Schedule
Period-I Period-II
(28APR19) (08MAY19)
Drug Administration
Drug Administration
Actual Time of Drug
Actual Time of Drug

Scheduled Time of
Scheduled Time of
Administration
Administration
Subject No.
(hours)
(hours)
(hours)
01 08:00 08:00 08:00 (hours)

08:00
02 08:00 08:00 08:00 08:00
03 08:01 08:01 08:01 08:01
04 08:01 08:01 08:01 08:01
05 08:02 08:02 08:02 08:02
06 08:02 08:02 08:02 08:02
07 08:03 08:03 08:03 08:03

Elected to withdraw from the trial due to
08 08:03 08:03 schedule conflict (family gathering) during
period-II check-in
09 08:04 08:04 08:04 08:04
10 08:04 08:04 08:04 08:04

Page 39 of 79
Period-I Period-II
(28APR19) (08MAY19)
Drug Administration
Drug Administration
Actual Time of Drug
Actual Time of Drug

Scheduled Time of
Scheduled Time of
Administration
Administration
Subject No.
(hours)
(hours)
(hours)
(hours)
11 08:05 08:05 08:05 08:05
12 08:05 08:05 08:05 08:05
13 08:06 08:06 08:06 08:06
14 08:06 08:06 08:06 08:06
15 08:07 08:07 08:07 08:07
16 08:07 08:07 08:07 08:07
17 08:08 08:08 08:08 08:08
18 08:08 08:08 08:08 08:08
19 08:09 08:09 08:09 08:09
20 08:09 08:09 08:09 08:09
21 08:10 08:10 08:10 08:10
22 08:10 08:10 08:10 08:10
23 08:11 08:11 08:11 08:11
24 08:11 08:11 08:11 08:11
25 08:12 08:12 08:12 08:12
26 08:12 08:12 08:12 08:12
27 08:13 08:13 08:13 08:13
28 08:13 08:13 08:13 08:13
The actual times of administration of study medication were recorded in the individual
subject’s case report form (CRF) in Module 5.3.1.2.

Page 40 of 79
9.4.6 Blinding
The study was designated as open-label, and all study staff personnel as well as the
subjects were unblinded to the treatment assigned in either period. However, the
bioanalysts were blinded to the sequence of administration of test drug and reference
drug formulation throughout the analysis procedure. Each sample tube was labelled
with the study number, study period, each subject’s assigned subject number, sampling
time point, and the sample number but did not include any reference to the treatment
regimen.
9.4.7 Prior and Concomitant Therapy

Subjects were not allowed to use prescription or over-the-counter products as per the
protocol medication exclusion criteria and restrictions.
A listing of all prior and concomitant medications taken before and during the study
can be found in Appendix 16.2.7.3.
9.4.8 Treatment Compliance

Dosing was completed under the direct supervision of the AXIS Clinicals LLC
Investigator or delegated staff to ensure treatment compliance and proper drug
administration. Immediately after the administration of either product, each subject’s
oral cavity and hands were checked to confirm medication and fluid consumption by
trained study personnel.
Subjects were instructed to swallow the medication as a whole without chewing,
crushing or biting.
Subjects were instructed to be in a seated or semi-recumbent position for at least 4
hours after dosing. Thereafter, subjects were allowed to engage in normal activities
while avoiding severe physical exertion.
Drinking water restriction was maintained one hour before dosing until two hours post-
dose, and all the subjects refrained from drinking water during this period.
Subjects were continuously monitored by AXIS Clinicals staff throughout the
confinement period of the study. During the washout interval between each study
period, staff was available for subject queries during regular working hours and via
phone after hours.
Drug Accountability:
Six bottles (06) (each bottle 100 capsules; i.e., 600 capsules) of Test product (T) and

Page 41 of 79
Reference product (R) were received from sponsor on 17APR19, and thirty (30)
capsules of Test product (T) and Reference product (R) were transferred to AXIS
Clinicals A17.0567 (fed) study. The supplied study medication was stored in the
pharmacy as per the recommended storage conditions.
For the conduct of the clinical phase, drug products were dispensed for period-I on
26APR19 and for period-II on 03MAY19 by the pharmacist at the clinical facility.
For each study period, Test product (T) and Reference product (R) were dispensed in
pre-labelled unit dose containers as per the following table:
Period (Date) Test Product (T) Reference Product (R)
I (26APR19) 14 + 02 (Extra Dose) 14 + 02 (Extra Dose)
II (03MAY19) 14 14
Standby units of Test product (T) and Reference product (R) were replaced along with
original container after dosing in both study periods.
The designated pharmacists ensured that the medication was not used for purposes
other than as directed by the protocol, and ensured that records of the receipt and
administration of the study medication were maintained.
No. of Units Drug Dispensing
No. of Units Total
Transferred Breakdown Current
Received Retention Total Inventory
Product to Fed Extra Total
from Samples Quantity Quantity Quantity Available
Study Doses (1) Inventory
Sponsor Dispensed Dosed Returned (2)
(A17.0567) Returned
Test
Product 600 30 300 30 28 NA 2 240 542*
(T)
Reference
Product 600 30 300 30 27 1 2 240 543*
(R)
Column
1 2 3 4 5 6 7 8 9
No.
(1) Total Inventory Available = Column 1 - Column 2 - Column 3 - Column 4.

(2) Current Total Inventory = Column 3 + Column 6 + Column 7 + Column 8.
*Includes standby units.
9.5 Pharmacokinetic and Safety Variables

9.5.1 Pharmacokinetic and Safety Measurements Assessed and Flow Chart
Pharmacokinetic Measurements:
The pharmacokinetic parameters of Cmax, AUC0-t, AUC0-, AUC%Extrapolation, Tmax, Kel,

Page 42 of 79
and T½ were calculated for plasma Lisdexamfetamine and Dextroamphetamine for each
subject and each treatment using drug concentration-time data by non-compartmental
method utilizing Phoenix WinNonlin® Software, Version 8.0 (Certara USA, Inc.).
Pre-Study Measurements:
The following assessments were completed during screening, within 28 days prior to
period-I dose administration: medical history including medications, allergies, and
health history; complete physical examination including vital signs (blood pressure,
respiratory rate, pulse rate, and temperature); 12-lead ECG; and clinical laboratory tests
[hematology, chemistry, urinalysis, test for drugs of abuse (Amphetamine, Barbiturates,
Benzodiazepines, Cocaine metabolites, Marijuana (THC), Methadone, MDMA (3,4-
methylenedioxy-methamphetamine [Ecstasy]), Opiates, Opioids, Phencyclidine (PCP)),
screen for infectious diseases (HIV 1 & 2, HBsAg and HCV), alcohol breath analysis,
FSH test, and serum pregnancy test (for all females)]. Inclusion/exclusion criteria were
also assessed during screening.
Demographic data including sex, date of birth, height, weight, BMI, history of
smoking, history of intake of abusive/recreational drugs, history of alcohol
consumption, history of blood donation, and history of participation in a drug research
study were collected for each subject. The mean, standard deviation, and minimum and
maximum values of height, weight, age, and BMI are presented for all subjects in
Appendix 16.2.4.
Clinical Entry Measurements:
All subjects were briefly evaluated before each confinement period to assess whether
they continued to meet the study inclusion/exclusion criteria (see sections 9.3.1 and
9.3.2 of this report). In addition, a drugs of abuse screen [Amphetamine, Barbiturates,
Benzodiazepines, Cocaine metabolites, Marijuana (THC), Methadone, MDMA (3,4-
methylenedioxy-methamphetamine [Ecstasy]), Opiates, Opioids, Phencyclidine (PCP)],
alcohol breath analysis, and urine pregnancy test (for all females) were performed
during each study period check-in. Subjects who had negative test results were checked
in to the study areas.
Vital Signs Measurement:
In each period, vital signs monitoring (blood pressure, pulse rate and temperature) were
collected in a sitting position prior to dosing. Vital signs (blood pressure and pulse rate)
were collected at 2.00, 12.00 and 24.00 hours after each dose and at ambulatory visits
(36.00, 48.00, and 72.00 hours post-dose).
All in-house and ambulatory vitals were collected within a window period of ± 30
minutes to the scheduled time except pre-dose vitals (for deviations, refer to Appendix
Page 43 of 79
16.2.2.2). Pre-dose vitals were collected within 90 minutes prior to dosing in each
period.
Vital signs results can be found in Appendix 16.2.8.2.
Adverse Event Monitoring:
Adverse event monitoring (subject well-being questionnaire) was done at pre-dose, at
2.00, 12.00 and 24.00 hours post-dose, and at ambulatory visits (36.00, 48.00, and
72.00 hours post-dose). All in-house and ambulatory adverse event monitoring (subject
well-being questionnaire) were collected within a window period of ± 30 minutes to the
scheduled time (for deviations, refer to Appendix 16.2.2.2), except pre-dose SWBQ.
Pre-dose SWBQ was collected within 90 minutes prior to dosing in each period.
ECG (12-Lead) Recording and Evaluation:
A 12-lead ECG was collected during the screening visit and was evaluated by the
attending physician. All the subject’s ECGs collected during the screening visit were
found to be within normal limits or considered not clinically significant by the
physician.
Physical Examinations:
A physical examination was conducted by the attending physician during the screening
visit. All the subject’s systems during screening were found to be normal or considered
not clinically significant by the physician.
Post-Study/Study Exit:
Study exit procedures were completed after the last scheduled blood sample collection
for all of the subjects except withdrawal and dropout subjects who completed exit
procedures at the time of their last visit.
All subjects were required to complete a post-study evaluation including post-study
vitals (blood pressure and pulse rate), clinical laboratory tests (chemistry and
hematology), and urine pregnancy test (for all females). All subjects completed the
post-study evaluation. Results of clinical laboratory tests and urine pregnancy test can
be found in Appendix 16.2.8.1. Vital signs results can be found in Appendix 16.2.8.2.
9.5.2 Appropriateness of Measurements

The time points chosen for pharmacokinetic assessments are based on the literature for
the pharmacokinetics of Lisdexamfetamine and Dextroamphetamine (reference
mentioned in section 15 of this report). The total volume of blood collected over the
course of the study for pharmacokinetic sampling for each subject was approximately
356 mL. The volume of blood collected over this time period was considered to have
Page 44 of 79
no effect on the plasma concentration data. Plasma concentrations of the Test product
(T) and Reference product (R) were measured in this study.
9.5.3 Pharmacokinetic Variable(s)

The following primary and secondary pharmacokinetic parameters were assessed:
Lisdexamfetamine and Dextroamphetamine:
Primary Parameters
Cmax Maximum measured plasma concentration over the time span

specified.
AUC0-t The area under the plasma concentration versus time curve, from time
0 to the last measurable concentration, as calculated by the linear
trapezoidal method.
AUC0- The area under the plasma concentration versus time curve from time
0 to time infinity. AUC0- is calculated as the sum of the AUC0-t plus
the ratio of the last measurable plasma concentration (Ct) to the
elimination rate constant Kel.
AUC0- = AUC0-t + Ct/Kel
Secondary Parameters
AUC%Extrapolation The % extrapolation will be calculated as, [AUC0-AUC0-t] *100

AUC0-
Tmax Time of the maximum measured plasma concentration. If the

maximum value occurs at more than one time point, Tmax is defined as
the first time point with this value.
Kel Apparent first order elimination rate constant calculated from a semi-
log plot of plasma concentration versus time point. The parameter will
be calculated by linear square regression analysis using the last 3 (or
more) non-zero plasma concentrations.
T½ The elimination or terminal half-life will be calculated as 0.693/Kel.
These parameters were derived individually for each analysed subject from the
concentration vs time data of Lisdexamfetamine and Dextroamphetamine in plasma.

Page 45 of 79
Values below the lower limit of quantification were set to zero. The pharmacokinetic
parameters were calculated by non-compartmental model using Phoenix WinNonlin®
Software, Version 8.0 (Certara USA, Inc.).
Refer to Appendix 16.2.6 for individual and mean pharmacokinetic parameters of
Lisdexamfetamine and Dextroamphetamine.
9.5.4 Drug Concentration Measurements

Blood samples were collected by direct venipuncture. A total of 28 venous blood
samples (1 x 6 mL) were collected in pre-labelled vacutainer tubes containing K2EDTA
during each study period.
The pre-dose (0.00 hour) venous blood sample (1 x 6 mL) was collected within 90
minutes prior to drug dosing in each study period. The post-dose venous blood samples
(1 x 6 mL) were collected at 0.08, 0.17, 0.33, 0.50, 0.67, 0.83, 1.0, 1.33, 1.67, 2.0, 2.33,
2.67, 3.0, 3.50, 4.0, 4.50, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0 and 72.0
The actual blood sample times for all post-dose samples were documented on the
relevant raw data forms. Blood samples between 0.08 hour to 24.00 hours collected
within two minutes of the scheduled time were not considered as protocol deviations.
Blood samples at 36.00, 48.00 and 72.00 hours post-dose collected within ± 30 minutes
of the scheduled time were not considered as protocol deviations.
Refer to Appendix 16.2.2.1 for sample deviations that occurred during the study.
Handling of Blood Samples:
Each blood sample was collected into a pre-labelled vacutainer tube containing
K2EDTA and the collected blood samples were kept in an ice-bath until centrifugation.
The samples collected at each time point in period-I and period-II were centrifuged
(3000 RPM at 4°C ± 3°C for 10 minutes) within 60 minutes of sample collection to
separate plasma. After the centrifugation, the vacutainers were returned to an ice-bath
while they were being pipetted into duplicate polypropylene transport tubes. The
duplicate transport tubes remained in an ice-bath until pipetting was complete and then
transferred directly to an Ultralow (-86 to -50°C) freezer until transferred to the
bioanalytical facility. The transfer of plasma samples to the freezer did not exceed 90
minutes from time of collection in the study unit. The duplicate samples were
inventoried and transferred to the in-house bioanalytical laboratory upon completion of
the clinical portion of the study (for deviations, refer to Appendix 16.2.2.2).

Page 46 of 79
Summary of Analytical Method

The plasma samples of subjects were analysed using a validated LC-MS/MS method
for Lisdexamfetamine and Dextroamphetamine at the bioanalytical facility of AXIS
Clinicals, 1711 Center Avenue West, Dilworth, MN 56529. The analysis was
conducted as per the applicable method no: AP 052_00 for Lisdexamfetamine and
Dextroamphetamine. Calibration curve of 0.5000 ng/mL to 100.0 ng/mL and 1.000
ng/mL to 200.0 ng/mL for Lisdexamfetamine and Dextroamphetamine was used to
determine the concentrations of Lisdexamfetamine and Dextroamphetamine
respectively in the samples of various subjects.
The analytical report, certificates of analysis of working standards / reference standards,
method validation report, 20% chromatograms and bioanalytical SOPs are provided in
Appendix 16.5 and 16.6 (bioanalytical and method validation report).
9.6 Data Quality Assurance

The investigator was well trained on GCP requirements, how to handle any kind of
emergencies during study conduct, and the contents of the protocol for conducting the
clinical study as per the protocol, ICH-GCP and applicable regulatory requirements.
Refer to Appendix 16.1.4 for Investigator’s CV with qualification details.
The quality assurance department performed in-process and retrospective audits
throughout the conduct of the study to ensure compliance to study protocol, in-house
standard operating procedures (SOPs), GCP, FDA bioanalytical guidance, and
applicable regulatory requirements.
Quality assurance personnel monitored the critical activities during the clinical phase
and bioanalytical phase of the study by performing in-process audits. The in-process
audits performed during the clinical phase of the study may include dispensing of
investigational products, ICF (Informed Consent Form) presentation, compliance
during check-in, dosing process, phlebotomy and vital examination, etc. The in-process
audits performed during the bioanalytical phase of the study may include instrument
set-up, standard curve preparation, sample extraction, internal standard preparation,
Quality Control (QC) sample preparation, etc.
Quality assurance personnel performed retrospective audits of the study raw data and
reports generated during the clinical and bioanalytical phase of the study. All of the
findings or observations were reported to the affected department for appropriate
corrective actions. After verification of the corrective actions for compliance, a quality
assurance statement of audit was issued. Quality assurance audit statements are
included in Appendix 16.1.8.
Page 47 of 79
Prior to submission of the data to quality assurance, individual departments such as

clinical and bioanalytical departments performed quality control checks on the
generated data and reports to ensure completeness and correctness of the data along
with compliance to applicable procedures. In addition, in-process quality control checks
were performed during the conduct of the study.
9.7 Statistical Methods Planned in the Protocol and Determination of Sample Size
9.7.1 Statistical and Analytical Plans
The data set for the estimation of pharmacokinetic parameters was prepared using
Phoenix WinNonlin® Software, Version 8.0 (Certara USA, Inc.). Estimation of
pharmacokinetic parameters was also carried out using the same software.
Descriptive statistics were computed and reported for all pharmacokinetic parameters of
The comparison of pharmacokinetic parameters of Test product (T) and Reference
product (R) was carried out using PROC GLM of SAS® Version 9.4 (SAS Institute Inc.,
USA).
Analysis of variance (ANOVA) was carried out by employing PROC GLM of SAS®
Version 9.4 (SAS Institute Inc., USA) for the Untransformed and Ln-transformed
pharmacokinetic parameters of Cmax, AUC0-t and AUC0- for Lisdexamfetamine and
Dextroamphetamine.
The ANOVA model included treatment received, the period in which it was given along
with the sequence in which each treatment was being received, and the subject effect
(nested within the sequence). Sequence effect was tested by using the subject nested
within sequence mean square from the ANOVA as the error term.
An F-test was performed to determine the statistical significance of the period, sequence
and treatment effects involved in the model at a significance level of 5% (alpha = 0.05).
Ratio analysis was computed for Ln-transformed pharmacokinetic parameters of
Lisdexamfetamine and Dextroamphetamine Cmax, AUC0-t and AUC0- data.
A 90% confidence interval for the ratio of the Test product (T) and Reference product
(R) averages (geometric least squares mean) were calculated using the LSM for Ln-
transformed Cmax, AUC0-t and AUC0- of Lisdexamfetamine and Dextroamphetamine
data.
The power of test to detect 20% difference between Test product (T) and Reference

Page 48 of 79
product (R) formulations was computed and reported for Lisdexamfetamine and
Dextroamphetamine.
Intra-subject variability was calculated for Ln-transformed pharmacokinetic parameters
of Cmax, AUC0-t and AUC0- of Lisdexamfetamine and Dextroamphetamine data.
Criteria for Determination of Bioequivalence was as follows:

Lisdexamfetamine and Dextroamphetamine:
The Test product (T) was considered as bioequivalent to the Reference product (R) if
the 90% confidence interval for geometric least squares mean ratios of Ln-transformed
pharmacokinetic Cmax, AUC0-t and AUC0- of Lisdexamfetamine and
Dextroamphetamine falls within the acceptable range of 80.00% to 125.00%.
T Vs R
Cmax 86.67-101.78
AUC0-t 89.16-103.72
AUC0- 89.31-103.62

Parameter Dextroamphetamine
T Vs R
Cmax 98.94-104.07
AUC0-t 99.42-108.09
AUC0- 99.86-108.69
Note: For active metabolite, Dextroamphetamine, the above data was provided as
supportive evidence of the comparable therapeutic outcome, but was not included in the
bioequivalence.
Details of statistical tests and results are discussed in section 11.4.1.
The detailed output of the statistical computations is presented in Appendix 16.1.9.
9.7.2 Determination of Sample Size

The anticipated intra-subject variability for Lisdexamfetamine Dimesylate Capsules
among primary pharmacokinetic parameters was ~16%. Hence, considering the CV of
~16%, the following estimates were considered for the computation of sample size:
T/R Ratio = 90-110%
Page 49 of 79
Intra-subject CV (%) = ~16%

Significance Level = 5%
Power = 80%
Bioequivalence Limits = 80.00-125.00% (Cmax, AUC0-t and AUC0-)
By considering the above data, 24 subjects were sufficient to establish bioequivalence
between Test and Reference formulations under fasting conditions with adequate
power. However, considering the withdrawals/dropouts due to adverse events or non-
compliance or due to personal reasons, 28 subjects were randomized and dosed.
9.8 Changes in the Conduct of the Study or Planned Analysis

The study was started as per the protocol bearing Study No.: A17.0566, Version No.:
02, Dated: 12MAR19, which was approved by IntegReview Institutional Review Board
on 19MAR19 without any changes.
10.0 STUDY SUBJECTS

10.1 Disposition of Subjects
Thirty-four (34) subjects were consented, twenty-eight (28) (01-28) subjects were
enrolled, and twenty-seven (27) (01-07 and 09-28) subjects completed the study.
Subjects checked into the clinical facility on 27APR19 for period-I and on 04MAY19
for period-II. Study check-in occurred on Day -1 prior to drug administration. The
subjects remained confined in the clinical facility until after the 24.00 hours post-dose
activities in each study period. Subjects returned to the clinical facility for the 36.00,
48.00, and 72.00 hour ambulatory activities.
The subjects were dosed according to the randomization schedule on 28APR19 for
period-I and on 05MAY19 for period-II.
Period Date of Check-in No. of Subjects Checked-in Date of Dosing No. of Subjects Dosed
I 27APR19 34 28APR19 28
II 04MAY19 27 05MAY19 27
Summary of Subject Disposition

Sequence
Total
RT TR
Subjects Randomized 14 14 28
Subjects Enrolled into the Study 14 14 28

Page 50 of 79
Sequence
Total
RT TR
Subjects Successfully Completed 14 13 27
Subjects Who Withdrew from Study Conduct
0 1 1*
(Voluntarily Withdrew)
Subjects Discontinued by the Investigator 0 0 0
Subjects Discontinued by the Sponsor 0 0 0
*For discontinued subjects, refer to Appendix 16.2.1.
10.2 Protocol Deviations

Protocol deviations which occurred at any time during the entire duration of the study
are presented in Appendix 16.2.2.
11.0 EFFICACY EVALUATION

11.1 Data Sets Analysed
Study was planned to randomize 28 subjects. Twenty-eight (28) (01-28) subjects were
enrolled and twenty-seven (27) (01-07 and 09-28) subjects completed the study. Plasma
samples of 28 (01-28) subjects were analysed for Lisdexamfetamine and
Dextroamphetamine.
Plasma concentrations of 28 (01-28) subjects were included in pharmacokinetic analysis
of Lisdexamfetamine.
Plasma concentrations of 27* (01-26 and 28) subjects were included in pharmacokinetic
analysis of Dextroamphetamine.
Plasma concentrations of 27# (01-07 and 09-28) subjects were included in statistical
analysis of Lisdexamfetamine.
Plasma concentrations of 26*# (01-07, 09-26 and 28) subjects were included in statistical
analysis of Dextroamphetamine.
Plasma concentrations of 27 (01-26 and 28) subjects were included in bioequivalence
evaluation of Lisdexamfetamine.
Note:
*The plasma samples for subject no. 27 were analysed, presented, and not considered
for pharmacokinetic analysis and statistical analysis as per protocol sections 12.1
(Sample Analysis), 14.3 (Pharmacokinetic Analysis) and 14.4 (Statistical Analysis) for
Dextroamphetamine, since subject no. 27 had a pre-dose plasma concentration value is
Page 51 of 79
greater than 5% of Cmax.

#
The plasma samples for subject no. 08 were analysed, presented, and considered for
pharmacokinetic analysis and not considered for statistical analysis as per protocol
sections 12.1 (Sample Analysis), 14.3 (Pharmacokinetic Analysis) and 14.4 (Statistical
Analysis) for Dextroamphetamine and Lisdexamfetamine, since subject no. 08
completed one study period, hence subjects was excluded from the statistical analysis
(subjects excluded from efficacy analysis are provided in Appendix 16.2.3).
11.2 Demographic and Other Baseline Characteristics

Demographic data for the enrolled subjects and the subjects who completed the study
are summarized in Table 4. A by-subject listing of the demographic data are provided
in Appendix 16.2.4.
Table 4 Summary of Demographic Characteristics1 of Subjects at Enrollment and

Completion
Enrolled Completed
N = 28 N = 27
Gender, N (%)
Males 15 (53.6%) 14 (51.9%)
Females 13 (46.4%) 13 (48.1%)
Race, N (%)
American Indian/Alaskan Native 0 (0.0%) 0 (0.0%)
Asian 3 (10.7%) 2 (7.4%)
Black or African American 4 (14.3%) 4 (14.8%)
Native Hawaiian/Pacific Islander 0 (0.0%) 0 (0.0%)
White 18 (64.3%) 18 (66.7%)
Hispanic2 3 (10.7%) 3 (11.1%)
Other 0 (0.0%) 0 (0.0%)
Age (years)
Mean ± SD 39.75 ± 16.32 38.89 ± 16.61
Median 39.00 39.00
Range 18-75 18-75

Page 52 of 79
Enrolled Completed
N = 28 N = 27
Age Groups, N (%)
< 18 years 0 (0.0%) 0 (0.0%)
18 – 40 years 17 (60.7%) 16 (59.3%)
41 – 64 years 8 (28.6%) 8 (29.6%)
65 – 75 years 3 (10.7%) 3 (11.1%)
> 75 years 0 (0.0%) 0 (0.0%)
Height (m)
Mean ± SD 1.70 ± 0.10 1.70 ± 0.10
Median 1.70 1.70
Range 1.530-1.935 1.530-1.935
Weight (kg)
Mean ± SD 77.54 ± 14.38 77.51 ± 14.65
Median 77.90 77.30
Range 53.65-114.45 53.65-114.45
2
BMI (kg/m )
Mean ± SD 26.82 ± 3.51 26.83 ± 3.58
Median 27.21 27.33
Range 19.87-31.72 19.87-31.72
Tobacco User3
Yes 0 (0.0%) 0 (0.0%)
No 28 (100.0%) 27 (100.0%)
1
Determined at screening.
2
Subjects who self-identify themselves as both Hispanic and other race(s) are included as Hispanic.
3
Defined as current tobacco user.
11.3 Measurements of Treatment Compliance

All subjects included in the study fulfilled all the study requirements during the
selection process. After being enrolled into the study, all study subjects were in
compliance to dietary restrictions as well as pre-dose and post-dose water restrictions.
Posture compliance after drug administration was maintained by the study subjects as
per protocol.

Page 53 of 79
11.4 Pharmacokinetic Results and Tabulations of Individual Subject Data

11.4.1 Analyses of Pharmacokinetics
Plasma Dextroamphetamine concentrations were determined by a validated and
sensitive bioanalytical LC-MS/MS method. Details of these analyses are provided in the
Bioanalytical Report Module 5.3.1.4.
Pharmacokinetic analysis on the plasma concentrations for Lisdexamfetamine and
Dextroamphetamine was carried out for the Test product (T) and Reference product (R)
to determine the pharmacokinetic parameters of Cmax, AUC0-t, AUC0-, AUC%Extrapolation,
Tmax, Kel, and T½ were calculated in each individual subject by non-compartmental
method using Phoenix WinNonlin® Software, Version 8.0 (Certara USA, Inc.).
The mean and SD pharmacokinetic parameters of Lisdexamfetamine and
Dextroamphetamine for Reference product (R) and Test product (T) are summarised in
the following tables.
Refer to Appendix 16.2.6 for individual and mean pharmacokinetic parameters of Cmax,
AUC0-t, AUC0-, AUC%Extrapolation, Tmax, Kel, and T½ of Lisdexamfetamine and
Dextroamphetamine.
Table 5 Treatment Means for Lisdexamfetamine Pharmacokinetic Parameters

Descriptive Statistics
Mean ± SD (Untransformed Data)
Parameter (Unit)
Reference Product (R) Test Product (T)
(N = 27) (N = 27)
Cmax (ng/mL) 47.87333 ± 23.667409 46.21333 ± 26.416391
AUC0-t (hr. ng/mL) 56.04504 ± 27.189234 53.67059 ± 24.506886
AUC0-∞ (hr. ng/mL) 56.60046 ± 27.206389 54.23936 ± 24.598969
AUC%Extrapolation 1.17455 ± 0.627572 1.20444 ± 0.600265
Tmax* (hr) 1.00 (0.67-1.67) 1.00 (0.67-1.69)
-1
Kel (hr ) 1.28592 ± 0.390344 1.27724 ± 0.433787
T1/2 (hr) 0.599 ± 0.2101 0.617 ± 0.2350
*For Tmax, Median has been represented instead of Mean and Range instead of SD.

Capsules 70 mg Test to Reference is provided below.

Page 54 of 79
Ln-transformed Data
(N = 27*)
Subject CV
(%)
Cmax
40.2529 42.8597 93.92 86.67-101.78 17.4 100
(ng/mL)
AUC0-t
48.2379 50.1601 96.17 89.16-103.72 16.4 100
(hr. ng/mL)
AUC0-
48.8294 50.7590 96.20 89.31-103.62 16.1 100
(hr. ng/mL)
Table 6 Treatment Means for Dextroamphetamine Pharmacokinetic Parameters
Descriptive Statistics
Mean ± SD (Untransformed Data)
Parameter (Unit)
Reference Product (R) Test Product (T)
(N = 26) (N = 26)
Cmax (ng/mL) 68.11077 ± 16.021726 69.25654 ± 17.391867
AUC0-t (hr. ng/mL) 1111.78650 ± 259.122448 1153.82815 ± 286.830346
AUC0-∞ (hr. ng/mL)# 1143.85188 ± 265.669252 1186.13815 ± 288.580247
AUC%Extrapolation# 3.06064 ± 1.212670 2.81269 ± 1.182865
Tmax* (hr) 3.50 ( 2.33-5.00) 3.27 (2.33-7.00)
Kel (hr-1) # 0.07006 ± 0.012171 0.06660 ± 0.012358
#
T1/2 (hr) 10.220 ± 1.9851 10.800 ± 2.2768
*For Tmax, Median has been represented instead of Mean and Range instead of SD.
#
For Reference Product (R), N = 25 for pharmacokinetic parameters of AUC0-∞, AUC%Extrapolation, Kel and T1/2
as the plasma concentrations of subject no. 10 in period-II did not exhibit the log-linear relationship at the
terminal elimination phase.

Capsules 70 mg Test to Reference is provided below.

Page 55 of 79
Ln-transformed Data
(N = 26*)
Subject CV
(%)
Cmax
67.3195 66.3431 101.47 98.94-104.07 5.3 100
(ng/mL)
AUC0-t
1123.2433 1083.5338 103.66 99.42-108.09 8.8 100
(hr. ng/mL)
AUC0-
1155.8341 1109.4460 104.18 99.86-108.69 8.8 100
(hr. ng/mL)
supportive evidence of the comparable therapeutic outcome, but was not included in the
bioequivalence.

Page 56 of 79
Figure 1 Linear Plot of Mean Plasma Concentrations Vs Time of Lisdexamfetamine
Figure 2 Semi - log Plot of Mean Plasma Concentrations Vs Time of Lisdexamfetamine

Page 57 of 79
Figure 3 Linear Plot of Mean Plasma Concentrations Vs Time of Dextroamphetamine
Figure 4 Semi - log Plot of Mean Plasma Concentrations Vs Time of Dextroamphetamine

Page 58 of 79
11.4.2 Statistical / Analytical Issues

ANOVA was computed for Untransformed and Ln-transformed pharmacokinetic
parameters of Cmax, AUC0-t and AUC0- for Lisdexamfetamine and Dextroamphetamine
using General Linear Model (PROC GLM) of SAS® Release 9.4 (SAS Institute Inc.,
USA).
Probability values for factors in the ANOVA model are given below.
Lisdexamfetamine:
ANOVA p-values ANOVA p-values
Parameter Untransformed Ln-transformed
Cmax AUC0-t AUC0- Cmax AUC0-t AUC0-
Sequence 0.1338 0.2158 0.2144 0.1061 0.0990 0.0988
Period 0.3133 0.4074 0.4075 0.7337 0.5681 0.5698
Treatment 0.4163 0.3730 0.3749 0.1946 0.3862 0.3820
For Untransformed and Ln-transformed data, it was found that the sequence and treatment
effects were statistically insignificant (p > 0.05) for Cmax, AUC0-t and AUC0-.
Dextroamphetamine:
Sequence 0.1418 0.0676 0.0627 0.1139 0.0827 0.0783
Period 0.9815 0.3038 0.3701 0.9966 0.2252 0.2716
Treatment 0.2647 0.1633 0.1260 0.3332 0.1541 0.1117
For Untransformed and Ln-transformed data, it was found that the sequence and treatment
effects were statistically insignificant (p > 0.05) for Cmax, AUC0-t and AUC0-.
11.4.2.1 Adjustments for Covariates

As this was a bioequivalence study, adjustments for covariates were not carried out.

Page 59 of 79
11.4.2.2 Handling of Dropouts or Missing Data

Missed Samples:
PERIOD-I
Subject No. Time Points (hr.) No. of Samples Missed Reason for Missed Samples
18 0.17 01 Due to difficult phlebotomy
27 36.00 01 Due to difficult phlebotomy
10 48.00 01 Due to schedule conflict
Total Number of Samples Missed in Period-I = 03
PERIOD-II
Subject No. Time Points (hr.) No. of Samples Missed Reason for Missed Samples
27 0.17 and 1.00 02 Due to difficult phlebotomy
Elected to withdraw from the trial due
08 0.00-72.00 28 to schedule conflict (family gathering)
during period-II check-in
Total Number of Samples Missed in Period-II = 30
Total Number of Missed Samples in Two Periods = 33
11.4.2.3 Interim Analysis and Data Monitoring

No interim analysis and data monitoring were carried out.
11.4.2.4 Multicentre Studies

This was a single centre study.
11.4.2.5 Multiple Comparisons / Multiplicity

As this was a single dose bioequivalence study, multiple comparisons were not carried
out.
11.4.2.6 Use of an “Efficacy Subset” of Subjects

As this was a bioequivalence study, this section is not applicable.
11.4.2.7 Active-Control Studies Intended to Show Equivalence

11.4.2.8 Examination of Subgroups

Page 60 of 79
11.4.3 Tabulation of Individual Response Data

Refer to Appendix 16.2.5 for concentration data, mean linear plot, semi-log plot and
linear & semi-log plots for individual subjects of Lisdexamfetamine and
Dextroamphetamine.
11.4.4 Drug Dose, Drug Concentration and Relationships to Response

As this was a bioequivalence study, drug concentration-response relationship was not
relevant because there was no measurement of pharmacodynamics or clinical effect.
11.4.5 Drug-Drug and Drug-Disease Interactions

11.4.6 By-Subject Displays

Individual concentration-time profiles (linear-linear and log-linear scaling) are provided
in Appendix 16.2.5 and Appendix 16.2.6, respectively.
11.4.7 Pharmacokinetic Conclusions

The 90% confidence interval for geometric least squares mean ratios of Ln-transformed
data of Cmax, AUC0-t and AUC0- of Lisdexamfetamine were calculated.
T Vs R
Cmax 86.67-101.78
AUC0-t 89.16-103.72
AUC0- 89.31-103.62
Based on these results, Lisdexamfetamine Dimesylate Capsules 70 mg (Test product) of

Norwich Pharmaceuticals, Inc. is bioequivalent with that of Vyvanse®
(Lisdexamfetamine Dimesylate) Capsules 70 mg (Reference product) of Shire US Inc.,
300 Shire Way, Lexington, MA 02421 when administered under fasting conditions.

Page 61 of 79
12.0 SAFETY EVALUATION

12.1 Extent of Exposure
Dose: A single oral dose of Lisdexamfetamine Dimesylate 70 mg × 1 Capsules of

either Test product (T) or Reference product (R) was administered with approximately
240 mL of drinking water at room temperature as per the randomization schedule by
study personnel.
The below tables summarize the actual number of treatments received by all dosed
subjects, the amount of drug dosed, and the total cumulative dose received by each
subject over the course of the study.
Subjects Exposed to the
Period No. Treatment Exposure
Treatment Groups
I 28APR19 28 (T-14 & R-14)
II 05MAY19 27 (T-14 & R-13)
Note: T: Test product, R: Reference product
Extent of Exposure for All Dosed Subjects

Subjects Who were Dosed in the Study
Total Number of
Subject Numbers Treatment Dose Total Exposure
Doses Taken
01-07 and 09-28 02 1 x 70 mg 2 x 70 mg
08 01 1 x 70 mg 1 x 70 mg
12.2 Adverse Events (AEs)

12.2.1 Brief Summary of Adverse Events
The subjects were monitored throughout the study for any adverse experiences.
Adverse events were collected and subsequently coded in tabular form using the
MedDRA Version 21.0 adverse event dictionary. The subjects were encouraged to
report signs, symptoms, and any changes in health to the clinic staff. The severity of
each adverse event was determined by the clinic staff based on observation and
questioning of the subject. The Investigator judged the relationship of the event to the
study treatments. None of the adverse events experienced by the subjects during this
study was judged as serious.
No serious adverse events (SAEs) were reported in the study.
Over all, twelve (12) adverse events were reported in five (05) subjects in entire
duration of the study.

Page 62 of 79
Period-I:
Total of seven (07) adverse events were reported in four (04) subjects in period-I. The
reported adverse events were mild in severity and were resolved completely on
follow-up.
Prior to period-II dosing:
Total of one (01) adverse event was reported in one (01) subject prior to period-II
dosing. The reported adverse event was mild in severity and was resolved completely
on follow-up.
Period-II:
Total of four (04) adverse events were reported in three (03) subjects in period-II. The
reported adverse events were mild in severity and were resolved completely on
follow-up.
No adverse events were reported in post-study lab investigations.
Adverse events that occurred over the course of the study are presented in Table 12.2.2.
The percentages in the table reflect the number of subjects who experienced the
specified AE at least once. An AE was defined as drug-related if the relationship was
considered “Certain”, “Probable/Likely”, or “Possible” by the Investigator.
A complete listing of all adverse events is presented in Appendix 16.2.7.

Study No.: A17.0566
Page 63 of 79
12.2.2 Display of Adverse Events

The incidence of AEs are summarized by treatment group in Table 6.
Table 7 Summary of Treatment-Emergent Adverse Events
Treatment T* : Adverse Events N = 28 a
Subjects Who Experienced Indicated AE at Least Once by Intensity and Relationship b Total No. of AEs c
Mild Moderate Severe Total
System Organ Preferred
Possible Unlikely Possible Unlikely Possible Unlikely Possible Unlikely Overall
Class Term
Gastrointestinal 01 [S17]
Dry mouth - - - - - 01 - 01
disorders 3.6%
General 01 [S08]
Hyperhidrosis - - - - - 01 - 01
disorders and 3.6%
administration 01 [S08]
Thirst - - - - - - 01 01
site conditions 3.6%
02 [S03 and
Headache - - - - - 02 - 02
Nervous system S17] 7.1%
disorders 01 [S17]
Dizziness - - - - - 01 - 01
3.6%
Psychiatric 01 [S23]
Mood altered - - - - - 01 - 01
disorders 3.6%
Total Number of
- 06 01 - - - - 06 01 07
AEs Reported
Total Number of
Subjects
Reporting at
- 04 01 - - - - 04 01 04*
Least One AE
by Intensity and
Relationship

Study No.: A17.0566
Page 64 of 79
Treatment T* : Adverse Events N = 28 a

Class Term
Total Number of
Subjects
Reporting At
- 04 01 - - - - 04 01 04*
Least One AE
Over the Course
of the Study
a
= Number of subjects dosed with Treatment.
b
= Total number of subjects reporting at least one incidence of respective adverse event.
(%) percentage of subjects reporting at least one incidence of respective adverse event.
Subject numbers of subjects reporting at least one incidence of respective adverse event.
c
= Total number of reported adverse events.
^ = N/A
*S17 had 3 AEs and S08 had 2 AEs by relationship.

Study No.: A17.0566
Page 65 of 79
Treatment R* : Adverse Events N = 27 a

Class Term
General 01 [S06]
Hyperhidrosis - - - - - 01 - 01
disorders and 3.7%
administration Injection site 01 [S23]
- - - - - - 01 01
site conditions joint pain 3.7%
01 [S03] 01 [S17]
Headache - - - - 01 01 02
Nervous system 3.7% 3.7%
disorders 01 [S17]
Dizziness - - - - - 01 - 01
3.7%
Total Number of
- 03 02 - - - - 03 02 05
AEs Reported
Total Number of
Subjects
Reporting at
- 03 02 - - - - 03 02 04*
Least One AE
by Intensity and
Relationship

Study No.: A17.0566
Page 66 of 79
Treatment R* : Adverse Events N = 27 a

Class Term
Total Number of
Subjects
Reporting At
- 03 02 - - - - 03 02 04*
Least One AE
Over the Course
of the Study
a
= Number of subjects dosed with Treatment.
b
= Total number of subjects reporting at least one incidence of respective adverse event.
(%) percentage of subjects reporting at least one incidence of respective adverse event.
Subject numbers of subjects reporting at least one incidence of respective adverse event.
c
= Total number of reported adverse events.
^ = N/A
*S17 had 2 AEs by relationship.
Note: Original terms (verbatim term or literal term) were coded into preferred term using MedDRA version 21.0.

Study No.: A17.0566

Page 67 of 79
12.2.3 Analysis of Adverse Events

Adverse events (AEs) were collected and tabulated. Adverse events were coded to
the preferred term using the Medical Dictionary for Regulatory Activities
(MedDRA) version 21.0. No formal statistical analyses were performed.
The most frequently reported adverse event (AE) following administration of Test
product (T) was headache which was reported by 02/28 (7.1%) subjects.
The most frequently reported adverse event (AE) following administration of
Reference product (R) was headache which was reported by 02/27 (7.4%) subjects.
12.2.4 Listing of Adverse Events by Subjects

A complete listing of adverse events experienced over the course of the study is
presented in Appendix 16.2.7.
12.3 Deaths, Other Serious Adverse Events and Other Significant Adverse Events
No deaths and serious adverse events were reported during the entire duration of the
study.
12.3.1 Listing of Deaths, Other Serious Adverse Events and Other Significant Adverse
Events
No deaths and serious adverse events were reported during the entire duration of the
study.
12.3.1.1 Deaths
No deaths were reported during the entire duration of the study.
12.3.1.2 Other Serious Adverse Events

No serious adverse events were reported during the entire duration of the study.
12.3.1.3 Other Significant Adverse Events

No other significant adverse events were reported during the entire duration of the
study.

Study No.: A17.0566

Page 68 of 79
12.3.2 Narratives of Deaths, Other Serious Adverse Events and Certain Other Significant
Adverse Events
No deaths, other serious adverse events and certain other significant adverse events
occurred in the entire duration of the study.
12.3.3 Analysis and Discussion of Deaths, Other Serious Adverse Events and Other
Significant Adverse Events
No deaths, other serious adverse events and certain other significant adverse events
occurred in the entire duration of the study.
12.4 Clinical Laboratory Evaluation

12.4.1 Listing of Individual Laboratory Measurements by Subject and Each Abnormal
Laboratory Values
All subjects’ laboratory values from screening (hematology, chemistry, urinalysis,
immunology) and post-study (hematology, chemistry); urine pregnancy test
completed at screening, each period check-in and post-study; urine drug screen and
alcohol breathalyzer completed at screening and each period check-in; and FSH test
completed at screening are presented in each subject’s case report form (CRF). A
complete by-subject listing of all laboratory results is presented in Appendix 16.2.8.1.
All clinical laboratory determinations are included in the subjects' CRFs provided in
Module 5.3.1.2.
12.4.2 Evaluation of Each Laboratory Parameter

12.4.2.1 Laboratory Values Over Time
Not applicable.
12.4.2.2 Individual Subject Changes

Not applicable.
12.4.2.3 Individual Clinically Significant Abnormalities

The subjects who participated in the study did not have any clinically significant
abnormalities during the conduct of the study. There were no clinically significant
values in the post-study laboratory reports during post-study safety measurements.

Study No.: A17.0566

Page 69 of 79
12.5 Vital Signs, Physical Findings and Other Observations Related to Safety
Vital signs were collected as per the protocol (section 11.11.1). All the subjects were
found to have normal vitals or vital values that were not clinically significant as
determined by the study physician. Physical exam findings performed at the time of
screening were found to be normal or not clinically significant per the study
physician. Electrocardiograms (ECG) collected at screening were evaluated and were
within normal limits or found to be not clinically significant per the study physician.
All laboratory investigations performed for the safety of the subjects are presented in
Appendix 16.2.8.1 and 16.2.8.2.
Individual vital signs collected at screening, during the study and at post-study,
along with physical examinations and electrocardiograms collected at screening, are
presented in each subject’s case report form (CRF) in Module 5.3.1.2.
12.6 Safety Conclusions

No serious adverse events (SAEs) were reported.
Overall, twelve (12) adverse events were reported in five (05) subjects over the
course of the study. All reported adverse events were mild in severity.
Five (05) AEs (headache, n = 2; hyperhidrosis, n = 1; dizziness, n = 1; injection site
joint pain, n = 1) occurred following oral administration of Reference product (R) of
Vyvanse® (Lisdexamfetamine Dimesylate) Capsules 70 mg. All reported adverse
events were resolved completely on follow-up.
Seven (07) AEs (headache, n = 2; hyperhidrosis, n = 1; thirst, n = 1; dizziness, n = 1;
dry mouth, n = 1; mood altered, n = 1) occurred following oral administration of
Test product (T) of Lisdexamfetamine Dimesylate Capsules 70 mg. All reported
adverse events were resolved completely on follow-up.
There were no clinically significant findings of all subjects who participated in the
post-study safety assesments. Thus, the test product and reference product were
comparable in safety profile.
Overall, Lisdexamfetamine Dimesylate Capsules 70 mg was well tolerated as a
single oral dose when administered under fasting conditions.

Study No.: A17.0566

Page 70 of 79
13.0 DISCUSSION AND OVERALL CONCLUSIONS

Pharmacokinetic Conclusion
The 90% confidence interval for geometric least squares mean ratios of Ln-
transformed data of Cmax, AUC0-t and AUC0- of Lisdexamfetamine were calculated:
T Vs R
Cmax 86.67-101.78
AUC0-t 89.16-103.72
AUC0- 89.31-103.62
Based on these results, Lisdexamfetamine Dimesylate Capsules 70 mg (Test

product) of Norwich Pharmaceuticals, Inc. is bioequivalent with that of Vyvanse®
(Lisdexamfetamine Dimesylate) Capsules 70 mg (Reference product) of Shire US
Inc., 300 Shire Way, Lexington, MA 02421 when administered under fasting
conditions.
Overall, Lisdexamfetamine Dimesylate Capsules 70 mg was well tolerated as a

single oral dose when administered under fasting conditions.

Study No.: A17.0566

Page 71 of 79
14.0 TABLES, FIGURES AND GRAPHS REFERRED TO BUT NOT INCLUDED

IN THE TEXT
14.1 Demographic Data
Refer to Appendix 16.2.4 for a detailed listing of demographic data.

Study No.: A17.0566

Page 72 of 79
14.2 Efficacy Data
Table 8 Statistical Comparisons of Pharmacokinetic Parameters for Test Product Vs.

Reference Product
Descriptive Statistics for Lisdexamfetamine Pharmacokinetic Parameters
Cmax AUC0-t AUC0-∞ AUC% Tmax Kel T1/2
Statistics
(ng/mL) (hr.ng/mL) (hr.ng/mL) Extrapolation (hr) (hr-1) (hr)
N 27 27 27 27 27 27 27
Minimum 16.2400 19.5026 20.1200 0.5368 0.67 0.6367 0.36
Test Mean 46.21333 53.67059 54.23936 1.20444 1.129 1.27724 0.617

Formulation
Median 36.8600 47.8495 48.4523 0.9999 1.00 1.2792 0.54
(T)
Maximum 133.9000 124.1308 124.9780 3.0686 1.69 1.9504 1.09
SD 26.416391 24.506886 24.598969 0.600265 0.2983 0.433787 0.2350
CV (%) 57.2 45.7 45.4 49.8 26.4 34.0 38.1
N 27 27 27 27 27 27 27
Minimum 22.3400 22.1202 22.9271 0.3843 0.67 0.6300 0.33

Mean 47.87333 56.04504 56.60046 1.17455 1.110 1.28592 0.599
Reference
Formulation Median 39.4100 47.8814 48.3917 1.0545 1.00 1.1957 0.58
(R)
Maximum 111.5000 113.7734 114.2885 3.5195 1.67 2.1008 1.10
SD 23.667409 27.189234 27.206389 0.627572 0.2722 0.390344 0.2101
CV (%) 49.4 48.5 48.1 53.4 24.5 30.4 35.1
ANOVA Significance Testing

Sequence 0.1338 0.2158 0.2144 0.1061 0.0990 0.0988
Period 0.3133 0.4074 0.4075 0.7337 0.5681 0.5698
Treatment 0.4163 0.3730 0.3749 0.1946 0.3862 0.3820

Study No.: A17.0566

Page 73 of 79
Geometric Least Square Mean, Ratios, 90% Confidence and Power for
Lisdexamfetamine
Ln-transformed Data
(N = 27*)
Subject CV
(%)
Cmax
40.2529 42.8597 93.92 86.67-101.78 17.4 100
(ng/mL)
AUC0-t
48.2379 50.1601 96.17 89.16-103.72 16.4 100
(hr. ng/mL)
AUC0-
48.8294 50.7590 96.20 89.31-103.62 16.1 100
(hr. ng/mL)
Descriptive Statistics for Dextroamphetamine Pharmacokinetic Parameters

Cmax AUC0-t AUC0-∞ AUC% Tmax Kel T1/2
Statistics
(ng/mL) (hr.ng/mL) (hr.ng/mL) Extrapolation (hr) (hr-1) (hr)
N 26 26 26 26 26 26 26
Minimum 44.1400 713.4760 736.8430 1.1980 2.33 0.0386 7.27
Test Mean 69.25654 1153.82815 1186.13815 2.81269 3.804 0.06660 10.800

Formulation
Median 66.1750 1132.4535 1159.0585 2.8795 3.27 0.0663 10.46
(T)
Maximum 117.2000 2093.2810 2118.6670 5.3700 7.00 0.0953 17.98
SD 17.391867 286.830346 288.580247 1.182865 1.2218 0.012358 2.2768
CV (%) 25.1 24.9 24.3 42.1 32.1 18.6 21.1
N 26 26 25 25 26 25 25
Minimum 43.6900 668.8120 684.7030 1.2270 2.33 0.0480 7.80
Mean 68.11077 1111.78650 1143.85188 3.06064 3.567 0.07006 10.220

Reference
Formulation Median 66.9450 1084.8335 1098.3010 2.8990 3.50 0.0726 9.54
(R)
Maximum 111.7000 1753.2840 1775.0680 6.7370 5.00 0.0889 14.45
SD 16.021726 259.122448 265.669252 1.212670 0.8055 0.012171 1.9851
CV (%) 23.5 23.3 23.2 39.6 22.6 17.4 19.4

Study No.: A17.0566

Page 74 of 79
ANOVA Significance Testing

Sequence 0.1418 0.0676 0.0627 0.1139 0.0827 0.0783
Period 0.9815 0.3038 0.3701 0.9966 0.2252 0.2716

Treatment 0.2647 0.1633 0.1260 0.3332 0.1541 0.1117
Geometric Least Square Mean, Ratios, 90% Confidence and Power for
Dextroamphetamine
Ln-transformed Data
(N = 26*)
Subject CV
(%)
Cmax
67.3195 66.3431 101.47 98.94-104.07 5.3 100
(ng/mL)
AUC0-t
1123.2433 1083.5338 103.66 99.42-108.09 8.8 100
(hr. ng/mL)
AUC0-
1155.8341 1109.4460 104.18 99.86-108.69 8.8 100
(hr. ng/mL)
supportive evidence of the comparable therapeutic outcome, but was not included in
the bioequivalence.
Refer to Appendix 16.2.5 for concentration data, linear plot, semi-log plot and linear
& semi-log plots for individual subjects of Lisdexamfetamine and
Dextroamphetamine.
Refer to Appendix 16.1.9 for detailed output of statistical computations
(documentation of statistical methods).

Study No.: A17.0566

Page 75 of 79
14.3 Safety Data
14.3.1 Displays of Adverse Events

Adverse events that occurred over the course of the study are presented in Table
12.2.2. Refer to Appendix 16.2.7 for a complete listing of AEs.
14.3.2 Listings of Deaths, Other Serious and Certain Other Significant Adverse Events
No deaths or serious adverse events were reported during the entire duration of the
study.
14.3.3 Narratives of Deaths, Other Serious and Certain Other Significant Adverse Events
No deaths or serious adverse events were reported during the entire duration of the
study.
14.3.4 Abnormal Laboratory Value Listings

The subjects who participated in the study did not have any clinically significant
abnormalities during the conduct of the study.
All abnormal laboratory values (not clinically significant (NCS)) are presented in
Appendix 16.2.8.1.

Study No.: A17.0566

Page 76 of 79
15.0 REFERENCE LIST

 IntegReview IRB Approved Protocol No.: A17.0566, Version No.: 01, Dated:
12MAR19.
 ICH E3 – Structure and Contents of Clinical Study Reports.
 ICH E6 – Good Clinical Practice.
 Prescribing Information of Vyvanse® (Lisdexamfetamine dimesylate) capsules,
70 mg. At:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf
 Draft Guidance on Lisdexamfetamine Dimesylate Capsules, 70 mg
(Recommended Sept 2008; Revised Oct 2017). At:
https://www.accessdata.fda.gov/drugsatfda_docs/psg/Lisdexamfetamine%20Di
mesylate_draft_Oral%20cap_RLD%2021977_RC10-17.pdf
 Guidance for Industry and Investigators: Safety Reporting Requirements for
INDs and BA/BE Studies (December 2012). At:
https://www.fda.gov/downloads/Drugs/Guidances/UCM227351.pdf
 Guideline for Industry: Clinical Safety Data Management: Definitions and
Standards for Expedited Reporting (March 1995). At:
https://www.fda.gov/downloads/drugs/guidances/ucm073087.pdf
 NIA Adverse Event and Serious Adverse Event Guidelines. At:
https://www.nia.nih.gov/research/dgcg/clinical-research-study-investigators-
toolbox/adverse-events
 Draft Guidance for Industry: Pregnant Women: Scientific and Ethical
Considerations for Inclusion in Clinical Trials (April 2018). At:
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInforma
tion/Guidances/UCM603873.pdf
 E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1) Guidance
for Industry (March 2018). At:
https://www.fda.gov/media/93884/download
 Guidance for Industry: Bioanalytical Method Validation (May 2018). At:
https://www.fda.gov/downloads/drugs/guidances/ucm070107.Pdf
 Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil,
October 2013). At:
http://www.up.ac.za/media/shared/Legacy/sitefiles/file/45/2875/declarationofhe
lsinki_fortaleza_brazil2013.pdf
 Draft Guidance for Industry: Bioequivalence Studies with Pharmacokinetic
Endpoints for Drugs Submitted Under an ANDA (December 2013). At:
Study No.: A17.0566

Page 77 of 79
 Guidance for Industry: Statistical Approaches to Establishing Bioequivalence

(January 2001). At:
 WHO-UMC Causality Categories:
https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausa
lity_assessment.pdf

Study No.: A17.0566

Page 78 of 79
16.0 APPENDICES
Appendix
Title
No.
16.1 Study Information
16.1.1 Protocol and Protocol Amendments
16.1.2 Sample Case Report Forms (Unique Pages Only)
List of IntegReview Institutional Review Board (Plus the Name
16.1.3 of the Committee Chair) and Representative Written Information
for Subject and Sample Consent Forms
List and Description of Investigators and Other Important
16.1.4
Participants in the Study Including Brief CVs
Signatures of Principal/Coordinating Investigators/Sponsor
16.1.5
Responsible Medical Officer
Listing of Subjects Receiving Rest Drug(s)/Investigational
16.1.6 Product(s) from Specific Batches, Where More than One Batch
was Used
16.1.7 Randomization Scheme and Codes
16.1.8 Audit Certificates
16.1.9 Documentation of Statistical Methods
Documentation of Interlaboratory Standardization Methods and
16.1.10
Quality Assurance Methods
16.1.11 Publications Based on the Study
16.1.12 Important Publications Referenced in the Report
16.2 Subject Data Listings
16.2.1 Discontinued Subjects
16.2.2 Protocol Deviations
16.2.2.1 PK Sample Collection Deviations
16.2.2.2 Other Protocol Deviations
16.2.3 Subjects Excluded from the Efficacy Analysis

Study No.: A17.0566

Page 79 of 79
Appendix
Title
No.
16.2.4 Demographic Data
16.2.5 Compliance and Drug Concentration Data
16.2.6 Individual Efficacy Response Data
16.2.7 Adverse Event Listings
16.2.7.1 Summary of Adverse Events by System Organ Class
16.2.7.2 Listing of Adverse Events by Subjects
16.2.7.3 Concomitant Medications
Listing of Individual Laboratory Measurements by Subject, when
16.2.8
Required by Regulatory Authorities
16.2.8.1 Listing of Individual Laboratory Measurements by Subject
16.2.8.2 Vital Signs
16.3 Case Report Forms
CRFs for Deaths, Other Serious Adverse Events and
16.3.1
Withdrawals for Adverse Events
16.3.2 Other CRFs Submitted
16.4 Individual Subject Data Listings
16.5 Bioanalytical Report
16.6 Method Validation Report

A170566 Study Report Body

Caricato da

Informazioni sul documento

Titolo originale

Copyright

Formati disponibili

Condividi questo documento

Condividi o incorpora il documento

Opzioni di condivisione

Hai trovato utile questo documento?

Questo contenuto è inappropriato?

Copyright:

Formati disponibili

A170566 Study Report Body

Caricato da

Copyright:

Formati disponibili

Clinical Study Report

Protocol No.: A17.0566

1.0 TITLE PAGE

An open label, randomized, two-treatment, two-sequence,

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

1.1 Signature Page

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

Name of Sponsor / Company: Individual study table (for national

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

Name of Sponsor / Company: Individual study table (for national

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

Name of Sponsor / Company: Individual study table (for national

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

Name of Sponsor / Company: Individual study table (for national

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

Name of Sponsor / Company: Individual study table (for national

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

Name of Sponsor / Company: Individual study table (for national

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

Name of Sponsor / Company: Individual study table (for national

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

Name of Sponsor / Company: Individual study table (for national

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

Name of Sponsor / Company: Individual study table (for national

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

Name of Sponsor / Company: Individual study table (for national

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

Name of Sponsor / Company: Individual study table (for national

Based on these results, Lisdexamfetamine Dimesylate Capsules 70 mg (Test product) of

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

3.0 TABLE OF CONTENTS FOR THE INDIVIDUAL CLINICAL STUDY REPORT

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

3.1 List of Tables

Table 1 Abbreviations and Specialist Terms .............................................................................. 20

Table 2 Schedule of Events ........................................................................................................ 29

Table 3 Identification of Investigational Products...................................................................... 36

Table 4 Summary of Demographic Characteristics1 of Subjects at Enrollment and Completion

Table 5 Treatment Means for Lisdexamfetamine Pharmacokinetic Parameters ........................ 53

Table 6 Treatment Means for Dextroamphetamine Pharmacokinetic Parameters ..................... 54

Table 7 Summary of Treatment-Emergent Adverse Events ....................................................... 63

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

3.2 List of Figures

Figure 1 Linear Plot of Mean Plasma Concentrations Vs Time of Lisdexamfetamine .............. 56

Figure 3 Linear Plot of Mean Plasma Concentrations Vs Time of Dextroamphetamine ........... 57

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

4.0 LIST OF ABBREVIATIONS AND DEFINITION OF TERMS

Table 1 Abbreviations and Specialist Terms

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

e.g. : for example

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

5.2 Ethical Conduct of the Study

5.3 Subject Information and Consent

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

6.0 INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE

Designation Name of the Individual Responsibility

Planning and scheduling of projects and delegation of

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc

adults following single doses of 30 mg to 70 mg Vyvanse® capsule.

K:\Common\REPORTS\A17.0566_Lisdexamfetamine Dimesylate Capsules 70 mg_Fasting\a170566-study-report-body.doc