Efficacy, safety, and optimal dose selection of beclomethasone dipropionate nasal aerosol for seasonal allergic rhinitis in adolescents and adults.

OBJECTIVE: Some patients with allergic rhinitis (AR) may prefer nonaqueous intranasal corticosteroid aerosols because of unwanted attributes of aqueous formulations. The mandatory removal of chlorofluorocarbon-propelled nonaqueous aerosols from the market limited available treatment options. To fulfill this unmet need, a nonaqueous, hydrofluoroalkane-propelled beclomethasone dipropionate (BDP) nasal aerosol was developed and approved for treatment of AR nasal symptoms. As part of the development program, this dose-ranging study evaluated three doses of BDP nasal aerosol to determine the optimally safe and effective dose for adolescent and adult patients (≥12 years old) with seasonal AR (SAR). METHODS: After a 7 to 21 day placebo run-in period, eligible patients with SAR were randomly assigned to once-daily BDP nasal aerosol 80 µg, 160 µg, 320 µg, or placebo. The primary endpoint was the change from baseline in average a.m. and p.m. patient-reported reflective total nasal symptom scores (rTNSS) over 2 weeks. Safety and tolerability were also assessed. A potential study limitation could be lack of objective assessment of AR symptoms. RESULTS: Significant improvements were seen in average a.m. and p.m. rTNSS (least squares [LS] mean treatment difference, -0.63; 95% CI: -1.13, -0.13; p = 0.013) as well as in average a.m. and p.m. instantaneous TNSS (iTNSS; LS mean treatment difference, -0.60; 95% CI: -1.09, -0.11; p = 0.016) with BDP nasal aerosol 320 µg/day compared with placebo. Although there were numerical improvements from baseline in patient-reported rTNSS and iTNSS with BDP nasal aerosol 80 µg and 160 µg, these doses did not achieve statistical significance compared with placebo. BDP nonaqueous nasal aerosol was well tolerated at all doses tested, with a safety profile comparable to that of placebo. CONCLUSIONS: These data indicate that 320 µg/day of BDP nasal aerosol is the optimally safe and effective dose for the treatment of SAR in adolescent and adult patients. Trial registration NCT: #NCT00854360.

Safety and efficacy of fluticasone furoate in pediatric patients with perennial allergic rhinitis.

OBJECTIVE: To evaluate the safety and efficacy of once-daily (QD) fluticasone furoate (FF) nasal spray in children with perennial allergic rhinitis (PAR). STUDY DESIGN: A global, randomized, double-blind, placebo-controlled study. SUBJECTS AND METHODS: Pediatric patients (aged 2-11 years; n = 558) with PAR received once-daily placebo, FF 110 microg, or FF 55 microg for 12 weeks. Efficacy was evaluated by nasal symptom scores. General safety and corticosteroid-specific safety (nasal and ophthalmic examinations, and hypothalamic-pituitary-adrenal assessments) were assessed. RESULTS: No findings of clinical concern were identified from the safety assessments. For primary efficacy analysis of mean change from baseline over the first 4 weeks of treatment in daily reflective total nasal symptom score, FF 55 microg demonstrated significant improvement (P = 0.003) compared with placebo; however, the improvement for FF 110 microg versus placebo did not reach statistical significance (P = 0.073). CONCLUSION: FF QD was well tolerated and demonstrated efficacy in children aged 2 to 11 years with PAR.

Comparison of cetirizine-pseudoephedrine and placebo in patients with seasonal allergic rhinitis and concomitant mild-to-moderate asthma: randomized, double-blind study.

BACKGROUND: Allergic rhinitis (AR) and asthma are common concurrent conditions. OBJECTIVES: To evaluate the effects of cetirizine hydrochloride (5 mg)-pseudoephedrine hydrochloride (120 mg) (cetirizine-D) twice daily on AR and asthma symptoms, pulmonary function, and asthma-related quality of life in 274 patients with confirmed seasonal AR and concomitant mild-to-moderate asthma. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, after a 1-week screening period, patients took cetirizine-D or placebo for 4 weeks. The primary efficacy variable, AR total symptom severity complex score, was derived from patient daily diary ratings of sneezing, runny nose, itchy nose, postnasal drip, and nasal congestion. Asthma symptom severity total scores were derived from twice-daily diary ratings of wheezing, coughing, shortness of breath, and chest tightness. Pulmonary function was tested at clinic visits and by patients each morning and evening. Patients completed the Asthma Quality of Life Questionnaire at each visit. All tests were 2-sided, with statistical significance at the .05 level. RESULTS: Cetirizine-D reduced total symptom severity complex scores by 42.3% overall vs 23.6% with placebo (P < .001). Asthma symptom severity total scores were significantly improved with cetirizine-D at most times vs placebo. Cetirizine-D treatment was also associated with significantly improved Asthma Quality of Life Questionnaire overall scores. Pulmonary function test results were neutral. Cetirizine-D was well tolerated, with discontinuation and adverse event rates similar to placebo. Somnolence occurred in 8 patients (5.8%) taking cetirizine-D and in 1 (0.7%) taking placebo. CONCLUSIONS: Treatment with cetirizine-D twice daily significantly reduced rhinitis and asthma symptoms and improved overall asthma quality of life in patients with seasonal AR and concomitant mild-to-moderate asthma.

Safety and efficacy of olopatadine hydrochloride nasal spray for the treatment of seasonal allergic rhinitis.

BACKGROUND: A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR). OBJECTIVE: To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo in patients with SAR. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 565 patients aged 12 to 80 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms and completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: Olopatadine spray (0.4% and 0.6%) was significantly superior to placebo for percentage change from baseline in overall reflective (P = .004 and P < .001, respectively) and instantaneous (P = .02 and P = .003, respectively) TNSSs. Also, 0.6% olopatadine was significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny and itchy nose, and itchy eyes; the instantaneous assessments of watery eyes; and the overall and all 7 domain scores of the RQLQ (P < .05). Olopatadine spray exhibited a safety profile comparable with that of placebo. CONCLUSIONS: Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs (reflective and instantaneous) and in quality-of-life variables in patients with SAR. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.

Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis--a pooled analysis of three studies.

Allergic rhinitis is one of the most common clinical conditions in children; however, data regarding the safety of antihistamines in children with seasonal allergic rhinitis are limiting. To evaluate the safety and efficacy of fexofenadine in children with seasonal allergic rhinitis, data were pooled from three, double-blind, randomized, placebo-controlled, parallel-group, 2-week trials in children (6-11 year) with seasonal allergic rhinitis. All studies assessed fexofenadine HCl 30 mg b.i.d.; two studies included fexofenadine HCl at 15 and 60 mg b.i.d. Patients (and investigators) reported any adverse events during the trial. Physical examinations, including measurements of vital signs and laboratory tests, were performed. Efficacy assessments (total symptom score and individual symptom scores) were evaluated. Exposure to fexofenadine HCl 30 mg b.i.d. and to any fexofenadine dose exceeded 10,000 and 17,000 patient days, respectively. Incidences of adverse events, and discontinuations because of adverse events, were low and similar across treatment groups. In the placebo group, 24.4% of subjects reported adverse events compared with 24.1% for fexofenadine HCl 30 mg b.i.d., and 28.4% for all fexofenadine-treated groups. The most common adverse event overall was headache (4.3% placebo; 5.8% fexofenadine HCl 30 mg b.i.d.; and 7.2% any fexofenadine doses). Treatment-related adverse events were similar across treatment groups with no sedative effects. Fexofenadine HCl 30 mg b.i.d. was significantly superior to placebo in reducing the total symptom score and all individual seasonal allergic rhinitis symptoms, including nasal congestion (p < 0.05). Fexofenadine, at doses of up to 60 mg b.i.d., is safe and non-sedating, and fexofenadine HCl 30 mg b.i.d. effectively reduces all seasonal allergic rhinitis symptoms in children aged 6-11 years.

Fexofenadine is efficacious and safe in children (aged 6-11 years) with seasonal allergic rhinitis.

BACKGROUND: This is the first prospective, randomized, double-blind, placebo-controlled study showing statistical improvement of an H(1)-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. OBJECTIVE: This randomized, placebo-controlled, parallel-group, double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. METHODS: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (+/-1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point. RESULTS: Fexofenadine was significantly superior to placebo in the primary efficacy analysis (P

Efficacy and safety of desloratadine 5 mg once daily in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Chronic idiopathic urticaria (CIU) has a major impact on patient well-being. Antihistamines are the first-line treatment for CIU; however, some cause sedation. OBJECTIVE: Our purpose was to study the efficacy and safety of desloratadine, 5 mg, a new H(1)-receptor antagonist, in patients with moderate to severe CIU. METHODS: This study was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial of 6 weeks' duration. RESULTS: Compared with placebo, desloratadine significantly improved the total CIU symptom score as well as pruritus, the number of hives, and the size of the largest hive. Overall therapeutic response and global CIU status improved significantly with desloratadine; interference with sleep was reduced and the performance of daily activities improved. Statistically and clinically significant improvements were seen within the first 24 hours of treatment and were sustained throughout the full duration of the study. The incidence of adverse events, including somnolence, was similar in the desloratadine and placebo groups. CONCLUSION: Desloratadine is a well-tolerated and effective treatment of CIU.

Efficacy and safety of desloratadine in the treatment of perennial allergic rhinitis.

BACKGROUND: The evidence base for the use of H1-antihistamines in the treatment of perennial allergic rhinitis is considerably smaller than it is in the treatment of seasonal allergic rhinitis. OBJECTIVE: We hypothesized that desloratadine, a new, nonsedating selective H1-antihistamine, would be efficacious and safe in the treatment of perennial allergic rhinitis. METHODS: In a multicenter, randomized, placebo-controlled, double-blind, parallel-group study, 676 patients with symptomatic perennial allergic rhinitis were randomly assigned to 4 weeks of treatment with either 5 mg of desloratadine once daily or placebo. Efficacy was assessed by using a morning-evening instantaneous total symptom score (TSS), which was composed of scores for 4 individual nasal symptoms (rhinorrhea, itching, sneezing, and postnasal drip) and 3 individual nonnasal symptoms (itching eyes, watering eyes, and itching of the ears or palate). Secondary outcome measures included a morning-evening reflective TSS, total nasal and nonnasal symptoms scores, and individual symptom scores. Safety evaluations, including 12-lead electrocardiograms, were performed. RESULTS: Six hundred thirty-four patients completed the study. Desloratadine consistently diminished perennial allergic rhinitis symptoms, reducing the morning-evening instantaneous TSS (P =.005), the morning-evening reflective TSS (P =.007), the morning-evening reflective total nonnasal score (P =.023), and the individual nasal symptom scores for rhinorrhea, nasal itching, sneezing, and postnasal drip/drainage (P =.05 to P =.013) during weeks 1 through 4. Improvement in symptoms was observed after the first dose. Dropouts, and the type and frequency of adverse events (headache, viral infection, pharyngitis, and upper respiratory tract infection), were similar in both treatment groups. No clinically significant changes in QTc intervals were observed. CONCLUSIONS: Desloratadine rapidly and safely reduced the symptoms of perennial allergic rhinitis, and its efficacy did not diminish during 4 weeks of treatment.

Omalizumab improves asthma-related quality of life in patients with severe allergic asthma.

BACKGROUND: We have previously shown that omalizumab, a recombinant humanized monoclonal anti-IgE antibody, reduces asthma exacerbations and decreases inhaled corticosteroid (ICS) requirement in patients with severe allergic asthma who were symptomatic despite moderate-to-high doses of ICSs. OBJECTIVE: The aim of the present study was to assess the effects of omalizumab on asthma-related quality of life (QOL). METHODS: These analyses were part of a multicenter, 52-week, randomized, double-blind, placebo-controlled study assessing the efficacy, safety, and tolerability of subcutaneous omalizumab (> or =0.016 mg/kg of IgE [in international unit per milliliter] per 4 weeks) in 525 adults with severe allergic asthma. A 16-week steroid-stable phase was followed by a 12-week steroid-reduction phase and a 24-week double-blind extension phase. The effect of treatment on asthma-related QOL was evaluated by using the Asthma Quality of Life Questionnaire (AQLQ) administered at baseline and at weeks 16, 28, and 52. RESULTS: The 2 treatment groups were comparable in terms of baseline AQLQ scores. At weeks 16, 28, and 52, omalizumab-treated patients demonstrated statistically significant improvements across all AQLQ domains, as well as in overall score. Moreover, a greater proportion of patients receiving omalizumab achieved a clinically meaningful improvement in asthma-related QOL during each phase of the study. Greater than 50% of both patients and investigators rated treatment similarly with omalizumab as excellent or good compared with less than 40% of placebo recipients. CONCLUSION: In patients requiring moderate-to-high doses of ICSs for severe allergic asthma, the measurably improved disease control afforded by add-on omalizumab therapy is paralleled by clinically meaningful improvements in asthma-related QOL.

Intranasal fluticasone propionate is effective for perennial nonallergic rhinitis with or without eosinophilia.

BACKGROUND: Although response to intranasal corticosteroid therapy has been reported in patients with nonallergic rhinitis with eosinophilic syndrome (NARES), efficacy specifically in non-NARES patients has not been fully characterized. OBJECTIVE: To evaluate the efficacy of intranasal fluticasone propionate (FP) in the treatment of patients with perennial nonallergic rhinitis, with and without nasal eosinophilia. METHODS: Data from 983 patients in three randomized, double-blind, placebo-controlled PNAR trials were integrated. Patients received a total daily dose of FP 200 microg (n = 332), FP 400 microg (n = 325), or placebo (n = 326) for 28 days. Patients were > or =12 years of age with perennial rhinitis and negative skin tests to all allergens relevant to the geographic region. Nasal eosinophils were evaluated using a five-point scale. Patients were classified as non-NARES with a point score of 0 (n = 674; 69%); patients with a point score between I and 4 were classified as NARES (n = 309; 31%). Efficacy of FP was evaluated by the mean change in total nasal symptom score (TNSS), a sum of patient ratings of nasal obstruction, postnasal drip, and rhinorrhea. RESULTS: Patients with either NARES or non-NARES had similar statistically significant improvement with FP 200 microg or 400 microg compared with placebo; thus, the total group comprising both varieties of rhinitis responded to FP. In the total population, both FP treatment groups showed significantly greater improvement in TNSS compared with placebo during each week of treatment (P < or = 0.002), with mean changes in TNSS for day 22 to day 28 ranging from -84 and -85 in the FP 200 microg and FP 400 microg groups, respectively, to -64 in the placebo group. The three study treatment groups had similar proportions of non-NARES (68 to 69%) and NARES (31 to 32%) patients at baseline. In the non-NARES subgroup, mean changes in TNSS for each treatment group were similar to changes seen in the total population. In the NARES subgroup, mean changes in TNSS for the FP 200 microg and placebo groups were similar to changes seen in the total population; mean change in TNSS for the FP 400 microg group was somewhat greater than changes seen in the total population. CONCLUSIONS: Intranasal FP is an effective treatment for perennial nonallergic rhinitis with or without nasal eosinophilia (NARES or non-NARES).