Subjects 12 years or older with a 2-year documented history of SAR and otherwise in good health were eligible for enrollment. All subjects had a positive skin test response to an appropriate tree and/or grass seasonal allergen within the 12 months before study initiation. Subjects were determined to be in good health based on medical history, physical examination, electrocardiogram (ECG), and routine laboratory tests (blood chemistry, complete blood count, and urinalysis). Women of childbearing potential agreed to use a medically accepted method of contraception during this study. All subjects, as well as a parent or guardian when appropriate, provided written informed consent.
At the screening and baseline visits, the signs and symptoms of allergic rhinitis were scored jointly by the investigator and subject (with assistance from the parent/guardian, if required). Evaluated nasal symptoms included rhinorrhea, nasal stuffiness/congestion, nasal itching, and sneezing. Evaluated nonnasal signs and symptoms included itching/burning eyes, tearing/watering eyes, redness of eyes, and itching of ears or palate. All symptoms were graded on a 4-point scale using the following system: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. For inclusion on the study, subjects had to have a nasal rhinorrhea score of at least 2, a total nasal symptom score of at least 6, and a total nonnasal score of at least 5.
Subjects who met the following criteria were excluded from participation: (1) chronic use of inhaled or systemic corticosteroids for treatment of asthma; (2) current or past history of clinically significant sinusitis or chronic purulent postnasal drip; (3) rhinitis medicamentosa; (4) a history of allergies to more than 2 classes of medications; (5) hypersensitivity to or intolerance of antihistamines; (6) an upper respiratory tract or sinus infection that required antibiotic treatment within the 14 days before study screening; (7) a viral upper respiratory infection within 7 days before study screening; (8) nasal structural abnormalities that significantly interfered with nasal air flow; (9) dependence on nasal, oral, or ocular decongestants, nasal topical antihistamines, or nasal corticosteroids; (10) use of immunotherapy unless on a regular maintenance schedule before screening and maintained on a schedule for the remainder of the study; (11) hypersensitivity to the study drug or its excipients; and (12) current pregnancy or lactation.
This was a randomized, multicenter, parallel-group, placebo-controlled, double-blind study. The study was conducted at 29 medical centers across the United States. Following an approximately 1-week screening period, eligible subjects were randomly assigned in a 1:1:1:1:1:1 ratio to 2 weeks of treatment with desloratadine, 2.5, 5, 7.5, 10, or 20 mg, or placebo. Randomization was performed in blocks of 6 using a computer-generated randomization schedule. Each dose of study drug was administered orally in the morning, at approximately the same time each day. There were 5 scheduled study visits; a screening visit, a baseline visit on treatment day 1, and follow-up visits on days 4, 8, and 15. A central institutional review board and/or a local ethical committee approved the study before initiation.
To ensure blinding, the desloratadine and placebo tablets were identical in appearance and were packaged identically. Each daily dose consisted of 2 tablets. Desloratadine and placebo tablets were supplied by Schering Corporation, Kenilworth, NJ. Compliance with study medication was assessed at each study visit by questioning the subject, reviewing the diary cards, and examining the subject's drug supply.
Use of the following medications was prohibited during the study: nasal cromolyn sodium, nedocromil, saline, atropine, ipratropium bromide, azelastine, and corticosteroids; oral corticosteroids, antihistamines, and decongestants; ocular decongestants, corticosteroids, and saline; topical anti-inflammatory agents; and inhaled, intravenous, rectal, intramuscular, or intra-articular corticosteroids, as well as high-potency dermatologic corticosteroids. Use of systemic antibiotics was also prohibited, unless the patient was on a stable dose. There was a prespecified washout period for each of the prohibited medications, ranging from 12 hours for ocular and nasal saline to 3 months for intramuscular or intra-articular corticosteroids. Patients were able to take any medication that was not restricted by the protocol and that would not be expected to interfere with the study. Acetaminophen was permitted to be taken as needed for appropriate indications.
Clinical outcome assessment
Beginning at least 3 days before the baseline visit and throughout the remainder of the study, subjects recorded the severity of their nasal and nonnasal symptoms twice daily based upon how they felt the previous 12 hours (reflective) and also at the time of assessment (instantaneous). The nasal (rhinorrhea, nasal stuffiness/congestion, nasal itching, and sneezing) and nonnasal (itching/burning eyes, tearing/watering eyes, redness of eyes, and itching of ears or palate) symptoms were individually graded using a 4-point scale (0 = none to 3 = severe). The total symptom score was the sum of the scores for the 4 nasal and 4 nonnasal symptoms.
To characterize the efficacy of desloratadine at the end of the dosing interval, 24-hour efficacy of the study medications was evaluated using the AM instantaneous data set (before the next morning dose). The primary outcome of this analysis was the 2-week average AM instantaneous total symptom score expressed as a mean change from baseline. Secondary outcomes included the mean AM/PM previous total nasal and total nonnasal scores and individual symptom scores. In addition, day 2 AM instantaneous total symptom scores were analyzed to assess the effectiveness of desloratadine 24 hours after the first dose.
Diary cards also were used to record use of study medication, use of concomitant medication, adverse events, and the daily number of hours the subject was exposed to outside air. The diary cards were collected and reviewed at each visit.
All randomized subjects who received at least 1 dose of study medication and had baseline and at least 1 postbaseline day of diary data were included in the primary intent-to-treat efficacy analyses. The safety analyses included all randomized subjects. Before combining data across centers, center-specific results were examined and the significance of the treatment-by-center interaction for the primary efficacy variable was examined. Data were analyzed using a two-way analysis of variance (ANOVA) that extracted sources of variation due to treatment and center. The primary comparison was based on the pairwise differences in least-squares means between desloratadine, 10 mg, and placebo (from the ANOVA) using a 5% significance level. If the desloratadine 10-mg treatment was significantly different from placebo, then all other doses of desloratadine were compared with placebo at the 5% (two-sided) level of significance without adjustment for the multiple comparisons. In addition, a test of trend for nondecreasing response with increasing desloratadine dose (0, 2.5, 5, 7.5, 10, and 20 mg) was evaluated using the same two-way ANOVA.
The study was designed to enroll 150 subjects per treatment group. The sample size was chosen to detect (with 90% power and a 5% significance level) a difference between treatment groups of 1.6 units or more in the mean change from baseline diary total symptom score, assuming a pooled SD of 4.25.
Laboratory tests (complete blood count, blood chemistry, urinalysis) were performed and a 12-lead ECG was obtained at screening and at the conclusion of the study. Vital signs and adverse events were evaluated at each study visit.