Cetirizine, loratadine, or placebo in subjects with seasonal allergic rhinitis: effects after controlled ragweed pollen challenge in an environmental exposure unit.

BACKGROUND: Allergic rhinitis affects nearly one in 10 Americans. Cetirizine is a newer once-daily selective H1-antagonist. In traditional clinical trials, cetirizine has been shown to be safe and effective for the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. OBJECTIVE: To better characterize the efficacy and onset of action of cetirizine in a more controlled but clinically relevant setting, this agent was compared with loratadine and placebo in patients with symptomatic seasonal allergic rhinitis undergoing controlled pollen challenge in an environmental exposure unit (EEU). METHODS: This was a double-blind, randomized, parallel-group study. After screening, patients were exposed to ragweed pollen (primed) in the EEU (up to six exposures), and those with qualifying symptom scores were randomized to controlled pollen exposure (two periods of 5.5 to 6.5 hours over 2 days) and once-daily treatment with 10 mg cetirizine (n = 67), 10 mg loratadine (n = 67), or placebo (n = 68). The mean ragweed pollen level was 3480 +/- 350 grains/m3 (standard deviation). The primary efficacy variables were the total symptom complex (TSC) and the major symptom complex (MSC) scores. Symptoms were evaluated every half hour in the EEU throughout the study. RESULTS: Cetirizine produced a 36.7% mean reduction in TSC scores overall versus 15.4% with loratadine and 12.0% with placebo (p < or = 0.01). Cetirizine also produced a 37.4% mean reduction in MSC scores overall versus 14.7% with loratadine and 6.7% with placebo (p < or = 0.01). Onset of action as assessed by reductions in TSC and MSC scores versus placebo was evident within 1 hour with cetirizine (p < or = 0.02) and 3 hours with loratadine (p < or = 0.03). The incidence of treatment-related side effects was similar among groups, with headache reported most commonly in each group. CONCLUSION: Cetirizine is well tolerated and effective in reducing symptoms of seasonal allergic rhinitis in patients undergoing controlled pollen challenge.

Comparative study of cetirizine and terfenadine versus placebo in the symptomatic management of seasonal allergic rhinitis.

BACKGROUND: Cetirizine is a new antihistamine with greater selectivity for the histamine H1 receptor and a low rate of hepatic metabolism. Cetirizine once daily is effective in the symptomatic treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. OBJECTIVE: The efficacy and safety of cetirizine 10 mg qd, terfenadine 60 mg bid, and placebo were compared in patients with seasonal allergic rhinitis. METHODS: A multicenter, prospective, double-blind, randomized, parallel study was conducted for 2 weeks during the ragweed pollen season in patients with documented allergic rhinitis. Total symptom complex and total symptom complex plus nasal congestion scores, global efficacy, overall satisfaction, and adverse events were assessed at baseline and after 1 and 2 weeks of treatment. RESULTS: Of the 311 patients randomized to treatment, 283 completed the study. Cetirizine produced a marked improvement in symptoms scores compared with placebo after 1 week of therapy (P = .001). By the end of week 1, total symptom complex scores were improved by 37% with cetirizine compared with 29% for terfenadine, and 23% for placebo. An overall treatment effect was evident at week 1 (P = .0019), with marked differences between cetirizine and both placebo (P = .0004) and terfenadine (P = .0464) but not between terfenadine and placebo (P = .1215). A more marked treatment effect was evident during the first week of the study; this appeared to be related to spontaneous resolution of symptoms, since mean pollen counts derived for each patient declined significantly each week of the study. Therapy was generally well tolerated. Headache was the most common side effect in each group. Four patients on cetirizine, one on terfenadine, and two on placebo withdrew because of side effects. Somnolence was reported in 12 patients on cetirizine (P < .05), 2 on terfenadine, and 3 on placebo. CONCLUSION: Cetirizine produced a greater improvement in symptoms of seasonal allergic rhinitis than terfenadine or placebo.

Comparative outdoor study of the efficacy, onset and duration of action, and safety of cetirizine, loratadine, and placebo for seasonal allergic rhinitis.

BACKGROUND: Cetirizine, a new once-daily highly specific H1-antagonist, has been shown in conventional studies to be efficacious in the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. OBJECTIVE: The efficacy, duration and onset of action, and safety of cetirizine, 10 mg once daily, was compared with that of loratadine, 10 mg once daily, and placebo in a field study of patients with seasonal allergic rhinitis. METHODS: This was a randomized, double-blind, parallel, double-dummy study conducted over 2 days in spring allergy season at outdoor parks in San Diego and Iowa City. Study medication was administered at 10:00 AM on both days. After screening, eligible patients completed rhinitis symptom diaries in the park hourly from 7:30 to 9:30 AM (baseline); at 10:30 AM and hourly from 11:00 AM to 4:00 PM (period I); at 6:00, 8:00, and 10:00 PM at home (period II); and the next day in the park hourly from 8:00 to 10:00 AM (period III), and from 11:00 AM to 4:00 PM (period IV). Major and total symptom complex scores, global efficacy and overall satisfaction, and adverse events were assessed. RESULTS: Of the 279 patients (140 men and 139 women; mean age, 29 years) randomized to treatment, 278 were included in the efficacy analysis. Cetirizine produced significantly greater mean reductions than loratadine or placebo in major symptom complex severity scores at all periods (p < or = 0.05), except period I for placebo. Cetirizine also produced mean reductions in total symptom complex severity scores that were superior to loratadine at every evaluation period (p < 0.05) and were statistically different from placebo at period II (p < 0.01). A rapid onset of action was observed with cetirizine, as was a better response pattern in the patient global assessment of efficacy compared with loratadine. Study medications were well tolerated; no patient stopped treatment because of side effects. The incidence of somnolence with cetirizine was 13% versus 2% with placebo (p < 0.05); headache occurred more frequently with loratadine (23%) than with cetirizine (11%, p = 0.03). CONCLUSIONS: Cetirizine relieved rhinitis symptoms more effectively and quickly than loratadine and placebo in this field study of seasonal allergic rhinitis. Both active agents were generally well tolerated.

Safety and efficacy of azelastine nasal spray (Astelin NS) for seasonal allergic rhinitis: a 4-week comparative multicenter trial.

BACKGROUND: Azelastine is a chemically novel investigational antiallergy drug with the ability to antagonize the effects of chemical mediators of the early- phase and late phase allergic responses suggesting its usefulness in the treatment of upper and lower airway diseases. OBJECTIVE: The objective of this 4-week, double- bind, multicenter trial was to evaluate the efficacy of azelastine nasal spray in subjects with seasonal allergic rhinitis. METHODS: Two hundred sixty-four subjects 12 years of age and older were randomized to receive either azelastine, 2 sprays/nostril qd; azelastine, 2 sprays/nostril bid; oral chlorpheniramine maleate, 12 mg bid; or placebo. The primary efficacy parameters were the changes in major and total symptom severity scores. RESULTS: Overall, across all 4 weeks of treatment, the mean percent improvements in the total and major symptom complex severity scores in both azelastine treatment groups were greater than those for the placebo group. For the azelastine 2 sprays bid group, the overall results were significant at P = .05 for the major symptom complex score and at .05 < P = .10 for the total symptom complex score versus placebo. For both azelastine treatment groups, improvements in all of the individual rhinitis symptoms were superior to those for the placebo group and, in general were clinically and statistically significant. Azelastine nasal spray was well tolerated; adverse experiences were generally application site reactions, mild to moderate, and not limiting to continued treatment. CONCLUSIONS: Azelastine nasal spray demonstrated broad clinical antirhinitis activity that for the 2 sprays/nostril bid dosage regimen was consistently clinically and statistically significant.

A dose-ranging study of the efficacy and safety of azelastine nasal spray in the treatment of seasonal allergic rhinitis with an acute model.

BACKGROUND: Oral azelastine, a nonsteroidal antiinflammatory respiratory investigational drug has demonstrated activity in the treatment of allergic rhinitis and asthma with a good safety profile. METHODS: Azelastine nasal spray was compared with sustained-release oral chlorpheniramine maleate and placebo for efficacy and safety in the treatment of seasonal allergic rhinitis in a double-dummy, two-center, 2-day, double-blind, randomized, dose-ranging, parallel-groups, onset and duration of action study. Two hundred sixty-four subjects reported to an outdoor park on Saturday morning during the height of the fall pollen season and remained there for 8 hours that day and the next to ensure maximal exposure to seasonal aeroallergens. Symptom diary cards were collected hourly Saturday from 8:00 AM to 10:00 AM (baseline period). Subjects who had sufficient symptoms were randomized into five groups and received medication at 10:00 AM and 10:00 PM on Saturday and at 10:00 AM on Sunday: azelastine 0.1% (1 spray [0.12 mg] per nostril every 12 hours, 2 sprays per nostril every every 12 hours, or 2 sprays per nostril once daily), Chlor-Trimeton Repetabs (12 mg twice daily), or placebo (twice daily). Diary cards were completed hourly (11:00 AM to 4:00 PM) and at 6:00, 8:00, and 10:00 PM on Saturday and again hourly on Sunday (from 8:00 AM to 4:00 PM) to evaluate rhinitis symptoms and adverse events. RESULTS: Two hundred fifty-nine subjects completed the study. The groups that received 2 sprays of azelastine per nostril once and twice daily and the chlorpheniramine group had statistically significantly more improvement in total rhinitis symptoms than the placebo group without serious adverse events. CONCLUSIONS: This study supports a once to twice daily dosing regimen for 2 sprays of 0.1% azelastine in the acute treatment of allergic rhinitis with onset of action within 2 to 3 hours.

A double-blind, controlled trial to assess the safety and efficacy of azelastine nasal spray in seasonal allergic rhinitis.

BACKGROUND: Azelastine solution is a topically (nasal) administered antiallergy drug with a preclinical profile suggestive of efficacy in patients with allergic rhinitis. OBJECTIVES: The study was designed to compare the effectiveness and safety of two dosages of azelastine nasal spray (2 sprays per nostril once daily and twice daily) with that of placebo in the treatment of patients with symptomatic seasonal allergic rhinitis. METHODS: Two hundred fifty-one patients (12 years of age or older) were randomized to treatment in this 2-week, double-blind, parallel-group study. Primary efficacy variables were Major Symptom Complex (nose blows, sneezes, runny nose, itchy nose, watery eyes) and Total Symptoms Complex (Major Symptom Complex plus itchy eyes/ears/throat/palate, cough, postnasal drip). RESULTS: Patients treated with azelastine had mean percent improvements in Total and Major Symptom Complex scores that were consistently superior to placebo at each evaluation point. Overall, improvements were statistically significant (p < or = 0.05) in the Total Symptoms Complex for both azelastine groups and in the Major Symptom Complex for the twice daily group with a trend toward statistical significance for the once daily group. Azelastine was superior to placebo in improving all individual rhinitis symptoms. Adverse experiences in the azelastine groups were minor and infrequent. CONCLUSION: The results support the efficacy and safety of azelastine nasal spray in the treatment of seasonal allergic rhinitis.

Effectiveness of azelastine nasal solution in seasonal allergic rhinitis.

Azelastine is a novel antiallergy medication currently under investigation for the treatment of allergic rhinitis and asthma. Pharmacologic studies in laboratory animals and in vitro model systems indicate that azelastine exerts multiple actions including modulation of airways smooth muscle response, interference with inflammatory processes, and inhibition of allergic reactions. In a previous controlled clinical trial, azelastine nasal solution (ASTELIN N.S.) demonstrated effectiveness in controlling symptoms of seasonal allergic rhinitis (SAR). The objective of this 2-week double-blind, parallel-group study was to further assess the effectiveness of azelastine nasal solution in improving allergic rhinitis symptoms. Two hundred forty-seven patients (> or = 12 years) with symptomatic SAR who satisfied a minimum symptoms score during a 1-week, single-blind, baseline evaluation period were randomized to receive azelastine 2 sprays per nostril bid, azelastine 2 sprays per nostril qd, chlorpheniramine 12 mg bid, or placebo using a double-dummy technique to insure blinding. The primary efficacy variables were changes in Major Symptom Complex (nose blows, sneezes, runny nose/sniffles, itch nose, and watery eyes) and Total Symptom Complex (Major plus itchy eyes/ears/throat/palate, cough, and postnasal drip) severity scores. Patients treated with azelastine nasal solution qd and bid had mean percent improvements in the Total and Major Symptom Complex severity scores that were clinically significant (> or = 50% improvement over placebo) after both weeks, at endpoint, and overall. The improvements for the azelastine bid group were statistically significant (P < or = .05) at all evaluation points. Adverse experiences occurred infrequently, and none was considered serious or potentially limiting to the clinical utility of the nasal solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Azelastine nasal spray in the management of seasonal allergic rhinitis.

Azelastine is a novel, investigational, antiallergy medication that inhibits the generation, release, and/or end-organ activity of multiple mediators of the inflammatory process in vitro and in vivo. Azelastine is capable of inhibiting both early-phase and late-phase allergic responses in animals and humans. In this 2-day trial in patients with seasonal allergic rhinitis, we evaluated the onset of action, duration of effect, and safety and efficacy of azelastine nasal solution (Astelin N.S.) in an outdoor, highly allergenic environment. Two hundred ninety-four patients who satisfied entry criteria were randomized to azelastine 2 sprays/nostril q24h or q12h, oral chlorpheniramine maleate 12 mg q12h, or placebo in this multicenter, double-blind, parallel-group study. Rhinitis symptoms were analyzed individually and combined as total and major symptom complexes. For both azelastine treatment groups, the overall mean percent improvements in the total and major symptom complex severity scores were statistically significant (P < or = .05) versus placebo. Improvements in rhinitis symptoms were observed by the second hour after administration of azelastine and lasted up to 24 hours. The therapeutic effect of azelastine was apparent for all rhinitis symptoms, not just one or a few symptoms. Seventy-three percent of the patients treated with azelastine reported overall improvement upon global assessment of their symptoms. Adverse effects with azelastine were generally mild or moderate. Azelastine nasal spray, administered either once or twice daily, was effective in treating the symptoms of seasonal allergic rhinitis and demonstrated a rapid onset of action with a duration of response lasting 12 to 24 hours.