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CLINICAL USE Clin Drug Invest 2001; 21 (1): 25-32

1173-2563/01/0001-0025/$22.00/0

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Efficacy and Tolerability of Once-Daily 5mg


Desloratadine, an H1-Receptor Antagonist,
in Patients with Seasonal Allergic Rhinitis
Assessment during the Spring and Fall Allergy Seasons
Eli O. Meltzer,1 Bruce M. Prenner,2 Anjuli Nayak 3 and the Desloratadine Study Group
1 Allergy and Asthma Medical Group and Research Center, San Diego, California, USA
2 Allergy Associates Medical Group, San Diego, California, USA
3 Peoria School of Medicine, University of Illinois, Peoria, Illinois USA

Abstract Objective: To evaluate the efficacy and tolerability of desloratadine 5mg once
daily, a new, selective, H1-receptor antagonist, for the treatment of patients with
seasonal allergic rhinitis (SAR) during the two major pollen seasons in the USA.
Design: Two multicentre, randomised, double-blind, placebo-controlled,
parallel-group investigations in patients with SAR are reported, one conducted
during the spring (172 and 174 patients in the desloratadine and placebo groups,
respectively) and the other during the fall (164 patients each in the desloratadine
and placebo groups) allergy season.
Study Participants: Patients 12 years of age or older with clinically symptomatic
SAR and a minimum 2-year history of SAR.
Interventions: Desloratadine 5mg or placebo once daily for 14 days following
a 1-week screening period.
Main Outcome Measures: The primary efficacy assessment was the mean
change from baseline in the average reflective am/pm total symptom score (TSS)
averaged over the 2-week study period.
Results: In both seasons, desloratadine 5mg once daily resulted in a significant
improvement in TSS for patients with SAR (p < 0.01 and p = 0.02, respectively)
over the 2-week study. Adverse events reported were mild to moderate in severity
and similar to placebo. Assessment of sedation and ECG data revealed no
clinically significant changes from baseline with desloratadine- or placebo-
treated patients.
Conclusion: Desloratadine 5mg once daily was effective and well tolerated in
the treatment of symptoms associated with SAR following the first dose of
therapy and continuing for the 2-week duration of the study during both the spring
and fall allergy seasons.
26 Meltzer et al.

Allergic rhinitis is estimated to afflict 10 to 30% including ketoconazole and erythromycin.[8,9] Also
of adults and up to 40% of children in the United in human studies, desloratadine has no clinically
States.[1] Prevalence studies of allergic rhinitis in significant effect on electrocardiographic para-
other parts of the world indicate that allergic dis- meters, even when administered in up to nine
ease is a worldwide problem and that it is on the times the recommended clinical dose (5mg) for 10
rise.[2,3] Symptoms of seasonal allergic rhinitis days.[10]
(SAR) pose a substantial disease burden to affected Desloratadine has been evaluated for the treat-
patients. ment of patients with SAR. In a dose-ranging study
Allergic rhinitis is the local manifestation of a the 5mg dose was determined to be the optimal
systemic atopic condition. The signs and symp- clinical dose for patients 12 years and older. The
toms are largely the result of the release of hista- following summarises the tolerability and efficacy
mine from mast cells and basophils, though other of the 5mg dose of desloratadine given once daily
mediators, cytokines, chemokines and eosinophils for 14 days to patients with documented SAR from
also play significant roles.[4] H1-receptor ant- two placebo-controlled trials, one conducted dur-
agonists are an important first-line management for ing the spring allergy season and the second during
the symptomatic relief of SAR. However, the use the fall allergy season.
of some agents in this class has been limited by
treatment failure, poor tolerability, adverse effects, Patients and Methods
drug interactions, and the need for frequent drug
administration; therefore, current agents have not General Study Designs
been ideal for all patients.
Both studies were multicentre, randomised,
Desloratadine is a new oral, potent, selective
double-blind, placebo-controlled, parallel-group
peripheral H1-receptor antagonist. Binding studies
investigations designed to ensure that 150 patients
have demonstrated that desloratadine is 14 to 17
were to be evaluable for each study group for the
times more potent than loratadine in inhibiting
primary endpoint. Patients enrolled were ≥12 years
radiolabelled mepyramine binding to H1-receptors
of age, of either gender and of any race, and had at
in membrane preparations from guinea pig brain least a 2-year documented history of SAR and a
and lung tissue.[5] In animal studies, desloratadine positive (prick or intradermal) skin test response to
is four times more potent than loratadine in block- the appropriate seasonal allergens within 12
ing the activity of histamine-induced mouse paw months prior to enrolment. All patients were clini-
oedema, and 10-fold more potent than loratadine cally symptomatic at both the screening and base-
in reducing guinea pig nasal response to histamine line visits with at least moderate nasal rhinorrhoea
challenge.[5] Desloratadine demonstrates H1-re- (i.e. score ≥2), a total nasal (nasal itching, nasal
ceptor specificity including 15- to 50-fold lower stuffiness/congestion, rhinorrhoea and sneezing)
affinity for muscarinic receptors (M1, M2, M4, M5) symptom score ≥6, and a total non-nasal (itching
compared with H1-receptors.[5] or burning eyes, itching of ears or palate, eye red-
In human pharmacokinetic and pharmaco- ness and eye tearing) symptom score ≥5 (table I).
dynamic studies, desloratadine has a relatively Patients were in general good health as confirmed
long elimination half-life (27 hours),[6][Schering- by routine laboratory and clinical testing. Clinical
Plough, data on file] supporting once-daily admin- laboratory tests (CBC, blood chemistries, urinaly-
istration. The pharmacokinetic profile of deslor- sis) were within normal limits or clinically accept-
atadine is not altered by coadministration with able to the investigator. Patients were free of any
food.[7] Clinical pharmacokinetic studies have clinically significant disease (e.g. haematopoietic,
documented no significant interaction with drugs cardiovascular, hepatic, renal, neurological, psy-
that inhibit the cytochrome P450 enzyme system, chiatric, autoimmune disease) that would interfere

© Adis International Limited. All rights reserved. Clin Drug Invest 2001; 21 (1)
Efficacy and Tolerability of Desloratadine 27

Table I. Severity score for signs and symptoms of allergic rhinitis primary assessment of efficacy was the change
Severity score
from baseline in the average reflective 12-hour
am/pm total symptom score (TSS). The TSS was
0 = None No signs/symptoms evident
determined by a summation of the individual nasal
1 = Mild Signs/symptoms clearly present but minimal
awareness; easily tolerated
and non-nasal symptom scores. The primary end-
point was the mean change from baseline in the
2 = Moderate Definite awareness of signs/symptoms,
which are bothersome but tolerable TSS averaged over the 2-week study period (i.e.
3 = Severe Signs/symptoms hard to tolerate; may cause
days 2 to 15). Other parameters evaluated included
interference with activities of daily living a change from baseline in morning instantaneous
and/or sleeping (end of dosage interval) total symptom scores.
Other efficacy assessments included total nasal
and non-nasal symptom scores. Tolerability evalu-
with the study evaluation. All patients provided ations included monitoring of adverse events,
written, informed consent and the study was per- physical examination changes, laboratory values,
formed in accordance with the Declaration of and ECGs obtained at baseline and at the end of the
Helsinki. treatment period.
Exclusion criteria included patients with: rhini-
Statistical Analysis
tis medicamentosa; clinically significant sinusitis
or chronic purulent postnasal drip; investigational A two-way analysis of variance (ANOVA) was
drug use within 30 days prior to screening; or used to analyse the primary efficacy variable in
women who were pregnant or nursing. Any patient order to identify sources of variation due to treat-
with an upper respiratory infection (URI) or sinus ment and centre. All patients receiving at least one
infection requiring antibiotics within 14 days of dose of study drug were included in the efficacy
screening or a viral URI within 7 days of screening analysis (intent-to-treat), and confirmatory ana-
and patients with nasal structural abnormalities lyses were based on evaluable patients who had no
that interfered with nasal airflow were also ex- protocol violations.
cluded. Additionally, patients receiving immuno-
therapy were excluded unless they were on a reg- Results
ular maintenance schedule for 6 months or more
that would be continued throughout the study. Spring Allergy Season
Excluded medications were asthma medications, In this study, 172 patients were randomised to
nasal, oral or ocular decongestants, nasal topical desloratadine 5mg and 174 to placebo during the
antihistamines, nasal corticosteroids, and systemic spring allergy season (i.e. April to June). Baseline
antibiotics. Eligible patients were randomised to demographics were similar between patients in the
receive either 5mg desloratadine or placebo using desloratadine 5mg group and the placebo group
a computer-generated schedule. (table II). Patients were predominantly white and
Patients completed a 1-week screening period between the ages of 18 and 65 years, and the mean
during which the severity of symptoms was re- duration of SAR was 17 years. Baseline 12-hour
corded twice a day for at least 3 complete days reflective am/pm TSS were similar in the
before the baseline visit. Symptoms were scored desloratadine and placebo groups (14.2 and 13.7,
based on a reflection of how patients felt over the respectively), as were nasal and non-nasal symp-
previous 12 hours (reflective) and how they felt at tom scores (table II).
the time of the assessment, and were recorded in a Desloratadine therapy reduced the 12-hour
diary twice daily [morning (am) and afternoon reflective am/pm TSS by 4.3 (a 28% reduction),
(pm)]. During the 2-week treatment period, the averaged over the 2-week study period. This reduc-

© Adis International Limited. All rights reserved. Clin Drug Invest 2001; 21 (1)
28 Meltzer et al.

Table II. Baseline demographics


Demographic Spring study Fall study
desloratadine 5mg placebo desloratadine 5mg placebo
(n = 172) (n = 174) (n = 164) (n = 164)
Age group (y)
12–17 26 22 14 26
> 18 146 152 150 138

Gender
Men 68 81 51 55
Women 104 93 113 109

Race
White 129 131 129 117
Black 20 25 20 26
Asian 6 5 4 4
Hispanic 12 9 10 17
Other 5 4 1 0

Mean duration of SAR (y) 18 17 19.8 20.2

Mean baseline nasal symptom score 7.8 7.7 9.2 9.2

Mean baseline non-nasal symptom score 6.4 6.1 7.8 7.9

Mean baseline total symptom score 14.2 13.7 17.0 17.1

tion was significant compared with placebo, where


the TSS was reduced by 2.5 (a 12.5% reduction),
averaged over the 2 weeks (p < 0.01) [fig. 1].
Desloratadine Placebo
Total symptom score reduction from baseline

Reductions in the 12-hour reflective am/pm TSS 0


ranged from 3.7 to 4.8 (a 25 to 30% reduction) for
patients receiving desloratadine compared with a −1
decrease in TSS of 1.6 to 3.2 (4 to 18% reduction)
in the placebo group. Analysis of response by −2
gender found no differences between men and
women. A significant reduction in the 12-hour re- −3
flective am/pm TSS with desloratadine vs placebo
was observed beginning as early as day 2 and this −4
*
persisted throughout the 2-week treatment period
(p < 0.01 vs placebo for all time-points) [fig. 2]. −5
Patients also evaluated their ‘instantaneous’
symptoms at the end of each drug administration
interval, which provided information relative to the Fig. 1. Primary efficacy end-point: average reduction in total
symptom scores (TSS) [average reflective 12-hour am/pm TSS]
24-hour duration of effect for desloratadine. At over days 2 to 15 for desloratadine 5mg and placebo during the
the earliest evaluation following the first dose, spring allergy season. * p < 0.01.

© Adis International Limited. All rights reserved. Clin Drug Invest 2001; 21 (1)
Efficacy and Tolerability of Desloratadine 29

Total symptom score duration of allergy symptoms was 20 years (table


Time II). Baseline 12-hour reflective am/pm TSS were
similar in the desloratadine and placebo groups
1

2
2

k
ee

ee
(17.0 and 17.1, respectively), as were nasal and
ay

ay

ay

W
D

0
non-nasal symptom scores (table II). The average
Desloratadine
baseline TSS of patients in the fall study was
Reduction from baseline

−1 Placebo
higher compared with that in the spring study.
−2 Based on the primary efficacy variable (12-hour
−3
reflective am/pm TSS averaged over days 2 to 15),
* desloratadine was significantly more effective than
−4 *
*
* placebo at reducing allergy symptoms during the
* fall allergy season. In the desloratadine 5mg treat-
−5

Fig. 2. Time-course for reduction in total symptom scores (TSS)


[average reflective 12-hour am/pm TSS] for desloratadine 5mg Nasal symptom scores
and placebo during the spring allergy season. * p < 0.01.
Time
Panel A

2
D 2
D 3
4

k
ee

ee
ay
ay
ay

W
D

patients receiving desloratadine had a significant 0


Reduction from baseline

Desloratadine
reduction in TSS of 2.9 from baseline compared −0.5 Placebo
with those receiving placebo, which decreased by
−1.0
1.5 (p < 0.01).
At the efficacy evaluation on day 2, total nasal −1.5
symptoms (12-hour reflective am/pm) were signif-
−2.0
*
icantly reduced from baseline in patients receiving * * *
desloratadine 5mg compared with placebo (1.9 −2.5 *
vs 0.9 reduction, respectively; p < 0.01). A signif-
icant effect in the desloratadine group was main-
tained at all evaluated time-points throughout the Non-nasal symptom score
2-week study (p = 0.01) [fig. 3a]. Likewise, the Time
reduction in total non-nasal symptom score from Panel B
1

2
2

D 3
4

k
ee

ee

baseline (12-hour reflective am/pm) was 1.7 in the


ay
ay
ay

W
D
D

0
desloratadine treatment group compared with 0.7
Reduction from baseline

in the placebo treatment group (p < 0.01) at the first −0.5 Desloratadine
Placebo
evaluation (day 2) [fig. 3b]. Moreover, a signifi- −1.0
cant reduction from baseline vs placebo was
−1.5
observed at all additional time-points (p < 0.01). * *
−2.0 * *
*
Fall Allergy Season −2.5

During the fall allergy season (August to


November), 164 patients were randomised to
desloratadine 5mg once daily and 164 to placebo Fig. 3. Time-course of reduction in (A) nasal and (B) non-nasal
total symptom scores (TSS) [average reflective 12-hour am/pm
for 14 days. The demographic characteristics of TSS] for desloratadine 5mg and placebo during the spring
both treatment groups were similar, and the mean allergy season. Panel A: * p ≤ 0.01; panel B: * p < 0.01.

© Adis International Limited. All rights reserved. Clin Drug Invest 2001; 21 (1)
30 Meltzer et al.

Analysis of response by gender found no differ-


Desloratadine Placebo ences between men and women.
Total symptom score reduction from baseline

−1 Tolerability Evaluation

−2 Data from both studies demonstrated a placebo-


like tolerability profile for desloratadine 5mg
−3 given once daily for 14 days. The pattern and inci-
−4
dence of total and treatment-related adverse events
were similar for desloratadine 5mg and placebo
−5 * (table IV). Total adverse events reported in both
studies were 40 to 49% for patients treated with
−6
desloratadine 5mg and 37 to 52% for patients
treated with placebo. Adverse events reported were
Fig. 4. Primary efficacy end-point: reduction in total symptom
scores (TSS) [average reflective 12-hour am/pm TSS over days mild to moderate in severity, and no serious
2 to 15] for desloratadine 5mg and placebo during the fall allergy adverse events were attributed to desloratadine
season. p = 0.02. therapy. The most frequent adverse event was
headache, occurring in 16 to 24% of patients
treated with desloratadine 5mg once daily; how-
ment group, a 5.1 decrease (30% reduction) over
ever, patients treated with placebo had a similar
baseline in TSS was observed versus a 3.8 decrease frequency of headache (14 to 27%) [table IV]. The
(22% reduction) in the placebo group (p = 0.02) incidence of somnolence was also similar for des-
[fig. 4]. These significant reductions in TSS were loratadine and placebo in both studies (table IV).
also observed for assessments at the first and No unusual or unexpected adverse events were
second week time-points of the study, for the over- reported in either study. Results of routine physical
all 2-week duration of the study, and when symp- examinations and laboratory tests (including eval-
tom scores were assessed for either nasal or non- uations of renal and hepatic function) were un-
nasal symptoms (table III). Patients receiving remarkable and no significant changes from base-
desloratadine 5mg once daily experienced a de- line were observed with desloratadine therapy. In
the spring study, five patients in the desloratadine
crease of 2.4 to 2.9 (26 to 32% reduction) in total
group discontinued treatment because of an ad-
nasal symptoms compared with 1.9 to 2.1 (21 to
verse event compared with 10 in the placebo group.
23%, p < 0.05) for placebo. Similarly, there was a Five patients discontinued treatment in the fall
decrease of 2.3 to 2.8 (30 to 37% reduction) in total study, and only one adverse event was considered
non-nasal symptoms versus 1.7 to 2.1 (21 to 25% treatment related. A similar number of patients dis-
reduction, p ≤ 0.04) in the placebo group (table III). continued in the placebo group.

Table III. Fall study. Changes in total nasal and non-nasal symptom scores in the fall study (am/pm prior 12-hour score)
Nasal score Non-nasal score
meana (%)b meana (%)b
desloratadine placebo desloratadine placebo
Week 1 –2.4 (26) –1.9 (20) –2.3 (30) –1.7 (21)
Week 2 –2.9 (32) –2.1 (23) –2.8 (37) –2.1 (25)
Weeks 1 and 2 –2.6 (28) –2.0 (21) –2.5 (33) –1.9 (22)
* p ≤ 0.05 for all values.
a Least square means based on two-way analysis of variance.
b Raw mean percentage change.

© Adis International Limited. All rights reserved. Clin Drug Invest 2001; 21 (1)
Efficacy and Tolerability of Desloratadine 31

Table IV. Incidence of treatment-emergent adverse events (AE) reported by ≥5% of participants in any treatment group, by body system/organ
class (all randomised participants)
No.a (%) of participants
spring study fall study
desloratadine 5mg placebo desloratadine 5mg placebo
(n = 172) (n = 174) (n = 164) (n = 164)
No. of participants (%) with any AEb 69 (40) 64 (37) 81 (49) 85 (52)
Headache 28 (16) 25 (14) 40 (24) 44 (27)
Pharyngitis 6 (3) 3 (2) 11 (7) 5 (3)
Mouth dry 5 (3) 3 (2) 8 (5) 2 (1)
Dysmnorrhoea 0 2 (2) 7 (6) 8 (7)
Somnolence 5 (3) 4 (2) 3 (2) 3 (2)
a Number of participants reporting adverse events at least once during the study. Some participants may have reported more than
one adverse event.
b Includes all treatment-emergent adverse events reported, without regard to relationship to treatment.

Assessment of ECG data revealed no clinically included the nasal and non-nasal symptoms asso-
significant changes from baseline between des- ciated with SAR in both studies for the full 2-week
loratadine- and placebo-treated patients. In the study period. Furthermore, improvement in
spring study, patients receiving desloratadine had symptoms was observed after only one dose of
a 2% reduction from baseline for the QTc interval desloratadine. Symptomatic improvement was
compared with a 3% reduction in patients receiv- maintained for the full 24-hour drug administra-
ing placebo. In the fall study, patients receiving tion interval and throughout the duration of the
either desloratadine or placebo had ≤0.3% reduc- studies. In addition, a reduction in both total nasal
tion in QTc interval from baseline. (nasal itching, nasal stuffiness/congestion, rhinor-
rhoea, sneezing) and total non-nasal (itching or
burning eyes, itching of ears or palate, eye redness
Discussion
or tearing) symptoms was seen, indicative of the
SAR is a highly prevalent condition causing breadth of desloratadine efficacy against the spec-
significant morbidity for chronic sufferers. People trum of SAR symptoms.
with SAR generally have predictable onset of In both of these placebo-controlled trials, the
allergic symptoms that can last through the allergy 5mg dose was well tolerated. Importantly, no effect
season if untreated. Tree sensitivities are often on ECG parameters was observed with deslorat-
present in early spring, followed by grasses and adine.
weeds in late summer through the fall.[11] Most
studies[12-16] reported in the literature with the Conclusion
newer H1-receptor antagonists were conducted
during the fall allergy season so there is less infor- Desloratadine 5mg once daily is effective for
mation on the efficacy of these agents during the the treatment of symptoms of both spring and fall
spring allergy season. seasonal allergic rhinitis, resulting in relief of nasal
Desloratadine 5mg once daily effectively re- and non-nasal symptoms that is maintained with
duced the symptoms of SAR during both the spring continued administration. Once-daily administra-
and fall allergy seasons as demonstrated in these tion provides full 24-hour improvement in symp-
two double-blind, placebo-controlled studies. toms. The tolerability profile of desloratadine is
Desloratadine administration resulted in a signifi- similar to placebo, with no somnolence or other
cant reduction of the total symptom scores, which significant CNS or cardiovascular adverse effects.

© Adis International Limited. All rights reserved. Clin Drug Invest 2001; 21 (1)
32 Meltzer et al.

Acknowledgements 10. Marino M, Glue P, Herron JM, et al. Lack of electrocardio-


graphic effects of multiple high doses of desloratadine. [ab-
Funding was provided by Schering-Plough Research stract] Allergy 2000; 55 Suppl. 63: 279
Institute, Kenilworth, New Jersey, USA. 11. Hadley JA. Evaluation and management of allergic rhinitis.
Med Clin North Am 1999; 83: 13-25
12. Day JH, Briscoe M, Widlitz MD. Cetirizine, loratadine, or
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