Search

BACKGROUND: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions.METHODS: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms.RESULTS: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; PCONCLUSIONS: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).

Background Breath-actuated inhalers (BAI) may simplify the delivery of inhaled medications compared with other devices. Objective To evaluate the efficacy and safety of beclomethasone dipropionate BAI versus matching placebo in adolescent and adult patients with persistent asthma. Methods This phase III, 12-week, double-blind study enrolled patients with asthma aged ≥12 years who were previously treated with a stable dose of inhaled corticosteroid or noncorticosteroid therapy. After a run-in period of 14 to 21 days, patients were randomly assigned in a 1:1:1 ratio to beclomethasone dipropionate BAI 80 or 160 micrograms/day (40 or 80 micrograms twice daily) or placebo BAI. The primary end point was the standardized baseline-adjusted trough morning forced expiratory volume in 1 second (FEV1) area under the effect curve from time 0 to 12 weeks (AUEC[0-12 weeks]). Secondary end points included peak expiratory flow, rescue medication use, asthma symptoms, and the time to withdrawal due to meeting predefined criteria for worsening asthma. Additional end points evaluated quality of life, instructions for use, and safety. Results The full analysis and the safety sets included 270 and 273 patients, respectively. Patients who received beclomethasone dipropionate BAI 80 or 160 micrograms/day had significant improvements in FEV1 AUEC(0-12 weeks) versus placebo (p ≤ 0.001). Improvements in secondary end points were also apparent in patients who received beclomethasone dipropionate BAI 80 or 160 micrograms/day compared with placebo. Patients who received beclomethasone dipropionate BAI 80 or 160 micrograms/day had greater increases in Asthma Quality of Life Questionnaire scores versus placebo patients at week 12. Of 98 patients who participated in the instructions-for-use substudy, 87 (88.8%) used the inhaler successfully on their first attempt. Treatment was generally safe and well tolerated. Conclusion Beclomethasone dipropionate BAI 80 and 160 micrograms/day were effective and well-accepted treatments in patients with asthma, with safety comparable to beclomethasone dipropionate delivered via a metered-dose inhaler.Clinical trial NCT02040779, www.clinicaltrials.gov .

Background: GSP301 is an investigational fixed-dose combination nasal spray that contains the antihistamine, olopatadine hydrochloride (HCl), and the corticosteroid, mometasone furoate. Objective: To evaluate the efficacy and safety of GSP301 in patients with seasonal allergic rhinitis (SAR). Methods: In this double-blind, randomized, parallel-group study, patients (≥12 years of age) with SAR were equally randomized to intranasal GSP301 (olopatadine 665 μg and mometasone 25 μg), olopatadine HCl (665 μg), mometasone furoate (25 μg), or placebo for 14 days of twice-daily treatment. The primary end point was the mean change from baseline in the average A.M. and P.M. 12-hour reflective Total Nasal Symptom Score (rTNSS) analyzed by using mixed-effect model repeated measures (p www.clinicaltrials.gov .

Background: Approximately 80% of patients with asthma and chronic obstructive pulmonary disease incorrectly use a metered-dose inhaler and, therefore, fail to obtain full benefit from their inhaler medication. Beclomethasone dipropionate (BDP) hydrofluoroalkane, an inhalation aerosol administered via a breath-actuated inhaler (BAI) has been designed to improve ease of use over press-and-breathe metered-dose inhalers by eliminating the need for hand-breath coordination. Objective: To present the mechanics of the BAI device, assess the minimum reliable inspiratory flow rate required to trigger an actuation, and evaluate if intended users can safely and effectively use the BDP BAI according to the instructions for use (IFU). Methods: Six random batches (three batches each of 40 μg and 80 μg) of 10 inhalers were evaluated for the minimum inspiratory flow rate required for actuation trigger. Each inhaler was tested for actuation at five flow rates: 12, 14, 16, 18, and 20 L/min. Simulated-use testing was conducted with 91 participants from six representative user groups in the United States to assess the use of a placebo-filled production-equivalent BDP BAI according to the IFU. Results: Across the 40-μg batches, 83% of the devices actuated at 16 L/min and 100% actuated at 18 and 20 L/min. For the 80-μg batches, 67% and 100% actuated at 18 L/min and 20 L/min, respectively. All the participants demonstrated successful use of the BDP BAI during the study session. Isolated safety-critical errors with the potential for no-dose delivery were recorded for 15 participants but were considered unrelated to the design of the IFU. Conclusion: The BDP BAI consistently triggered actuation at an airflow rate of 20 L/min and was successfully used based on guidance from the IFU only. This device provides an alternative for patients who find it difficult to use metered-dose inhaler devices correctly.

Background The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents. Objective ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals. Methods Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non–daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics. Results Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non–daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non–daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm. Conclusions Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.

Background Intranasal corticosteroids are the mainstay of allergic rhinitis (AR) treatment. Their potential to suppress the hypothalamic-pituitary-adrenal axis should be evaluated, especially after long-term daily use in children. Objective To evaluate the effects of treatment with non-aqueous beclomethasone dipropionate (BDP) nasal aerosol on hypothalamic-pituitary-adrenal axis function in children with perennial AR. Methods In this double-blinded, placebo-controlled, parallel-group study, patients (6–11 years old) with perennial AR were randomized (2:1) to BDP nasal aerosol at 80 μg/day (n = 67) or placebo (n = 32). The primary end point was change from baseline in 24-hour serum cortisol (SC) weighted mean for BDP nasal aerosol and placebo after 6 weeks of treatment, which was analyzed in the per-protocol population. Results The per-protocol population included 97 patients (BDP nasal aerosol, n = 66; placebo, n = 31). Baseline geometric mean SC weighted mean values were similar in the 80-μg/day BDP nasal aerosol and placebo groups (5.97 and 6.47 μg/dL, respectively). After 6 weeks' treatment, geometric mean values were 6.19 and 7.13 μg/dL, respectively, with no decrease from baseline in either group. Geometric mean SC ratio of BDP nasal aerosol at 80 μg/day to placebo was 0.91 (95% confidence interval 0.81–1.03), indicating predefined noninferiority. SC concentration-time profiles were similar for the placebo and 80-μg/day BDP nasal aerosol groups at baseline and week 6. BDP nasal aerosol at 80 μg/day was generally well tolerated. Conclusion In pediatric patients with perennial AR, 24-hour SC profiles were comparable for BDP nasal aerosol and placebo, indicating that once-daily BDP nasal aerosol treatment did not significantly affect hypothalamic-pituitary-adrenal axis function. Trial Registration ClinicalTrials.gov; NCT01697956.

Background Allergic rhinitis (AR) is an inflammatory condition of the nasal mucosa characterized by symptoms of nasal discharge, itching, sneezing, and congestion. Ocular symptoms are commonly associated with AR and include itching or burning, tearing or watering, and redness. Intranasal corticosteroids are a mainstay of treatment, and their effect on nasal symptoms is well described. Objective To demonstrate that a 14-day course of 200 μg/d of nasal fluticasone propionate is superior to placebo in relieving ocular symptoms associated with AR. Methods This was a randomized, double-blind, parallel group, multicenter study comparing 200 μg/d of fluticasone propionate with placebo in patients with seasonal allergic rhinitis. The primary end point was mean change from baseline in patient-rated reflective total ocular symptom score (rTOSS). Key secondary end points included mean change from baseline in the morning and evening rTOSS, end-of-treatment assessment of response, and effect on activities of daily living. The primary analysis was performed using analysis of covariance with a linear fixed-effects model. Results Fluticasone was statistically significantly more efficacious in reducing the ocular symptoms of AR than placebo. The least squares mean difference in the change from baseline of rTOSS was −0.36 ( P = .002). A statistically significant difference in mean change from baseline was observed in favor of fluticasone for morning and evening rTOSS. Significantly more patients taking fluticasone achieved an overall response compared with placebo. Fluticasone had a significantly greater effect on daily living activities and was well tolerated. Conclusion This study supports the efficacy of fluticasone in treating ocular symptoms associated with AR. Trial Registration clinicaltrials.gov Identifier: NCT01817790.

Breath-actuated inhalers (BAI) may simplify the delivery of inhaled medications compared with other devices.To evaluate the efficacy and safety of beclomethasone dipropionate BAI versus matching placebo in adolescent and adult patients with persistent asthma.This phase III, 12-week, double-blind study enrolled patients with asthma aged ≥12 years who were previously treated with a stable dose of inhaled corticosteroid or noncorticosteroid therapy. After a run-in period of 14 to 21 days, patients were randomly assigned in a 1:1:1 ratio to beclomethasone dipropionate BAI 80 or 160 micrograms/day (40 or 80 micrograms twice daily) or placebo BAI. The primary end point was the standardized baseline-adjusted trough morning forced expiratory volume in 1 second (FEV1) area under the effect curve from time 0 to 12 weeks (AUEC[0-12 weeks]). Secondary end points included peak expiratory flow, rescue medication use, asthma symptoms, and the time to withdrawal due to meeting predefined criteria for worsening asthma. Additional end points evaluated quality of life, instructions for use, and safety.The full analysis and the safety sets included 270 and 273 patients, respectively. Patients who received beclomethasone dipropionate BAI 80 or 160 micrograms/day had significant improvements in FEV1 AUEC(0-12 weeks) versus placebo (p ≤ 0.001). Improvements in secondary end points were also apparent in patients who received beclomethasone dipropionate BAI 80 or 160 micrograms/day compared with placebo. Patients who received beclomethasone dipropionate BAI 80 or 160 micrograms/day had greater increases in Asthma Quality of Life Questionnaire scores versus placebo patients at week 12. Of 98 patients who participated in the instructions-for-use substudy, 87 (88.8%) used the inhaler successfully on their first attempt. Treatment was generally safe and well tolerated.Beclomethasone dipropionate BAI 80 and 160 micrograms/day were effective and well-accepted treatments in patients with asthma, with safety comparable to beclomethasone dipropionate delivered via a metered-dose inhaler.Clinical trial NCT02040779,ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov"www.clinicaltrials.gov/ext-link.

Background: It is unclear what constitutes a clinically meaningful response for allergic rhinitis (AR) outcomes. The objectives of these post hoc analyses were (1) to define a clinically meaningful response using novel efficacy analyses (including a responder analysis), and (2) to compare the efficacy of MP29-02 [a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP)] with commercially available FP, AZE and placebo in seasonal AR (SAR) patients, using these novel analyses. Methods: 610 moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Change from baseline in the reflective total nasal symptom score (rTNSS) over 14 days was the primary outcome. Post hoc endpoints included the sum of nasal and ocular symptoms (rT7SS), efficacy by disease severity and by predominant nasal symptom, and a set of responder analyses. Results: MP29-02 most effectively reduced rT7SS (relative greater improvement: 52% to FP; 56% to AZE) and both nasal and ocular symptoms irrespective of severity. More MP29-02 patients achieved a ≥30, ≥50, ≥60, ≥75 and ≥90% rTNSS reduction, which occurred days faster than with either active comparator; MP29-02 alone was superior to placebo at the ≥60% (or higher) threshold. One in 2 MP29-02 patients achieved a ≥50% rTNSS reduction and 1 in 6 achieved complete/near-to-complete response. Only MP29-02 was consistently superior to placebo for all patients, whatever their predominant symptom. Conclusions: MP29-02 provided faster and more complete symptom control than first-line therapies. It was consistently superior irrespective of severity, response criteria or patient-type, and may be considered the drug of choice for moderate-to-severe AR. These measures define a new standard for assessing relevance in AR.

An aerosol formulation may be preferred by some allergic rhinitis (AR) patients, to avoid the "wet feeling" and nasal runoff associated with aqueous nasal corticosteroid sprays. Beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol is a recently developed, nonaqueous, nonchlorofluorocarbon formulation of BDP for the treatment of AR. This study was designed to evaluate the efficacy, safety, and quality-of-life benefits of BDP nasal aerosol in subjects with seasonal AR (SAR). Eligible subjects (≥12 years of age) enrolled in this 2-week study were randomized to either BDP nasal aerosol at 320 μg/day (n = 169) or placebo (n = 171). Efficacy assessments included reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS, respectively), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, reflective and instantaneous total ocular symptom scores (rTOSS and iTOSS, respectively), and physician-assessed total nasal symptom score (PNSS). Safety and tolerability were also assessed. Subjects receiving BDP nasal aerosol showed a significantly greater improvement from baseline in average A.M. and P.M. rTNSS versus placebo (treatment difference, -0.91; 95% confidence interval, -1.3, -0.5; p < 0.001) over 2 weeks of treatment. Greater improvements in rTNSS with BDP nasal aerosol compared with placebo were evident by day 2 and were maintained throughout the treatment period. Similarly, significant improvements were seen with BDP nasal aerosol in iTNSS (p < 0.001) and RQLQ score (p = 0.005) compared with placebo. Treatment with BDP nasal aerosol also resulted in greater improvements in rTOSS (p = 0.002), iTOSS (p = 0.003), and PNSS (p < 0.001) relative to placebo. BDP nasal aerosol was well tolerated and the overall safety profile was similar to placebo. Results from this clinical study indicated that BDP nasal aerosol provided significant AR symptom relief and was well tolerated in patients with SAR with an overall safety profile similar to placebo. Clinicaltrials.gov identifier: NCT01024608.

Background A proof-of-concept study suggested that combination therapy with commercial azelastine hydrochloride nasal spray and fluticasone propionate nasal spray significantly improved nasal symptoms of seasonal allergic rhinitis compared with either agent alone. Objective To compare an azelastine-fluticasone combination nasal spray administered in a single-delivery device with a commercially available azelastine nasal spray and fluticasone nasal spray. Methods This 14-day, multicenter, randomized, double-blind study was conducted during the Texas mountain cedar season. After a 5-day placebo lead-in, 610 patients with moderate-to-severe nasal symptoms were randomized to treatment with (1) azelastine nasal spray, (2) fluticasone nasal spray, (3) combination azelastine and fluticasone nasal spray, or (4) placebo nasal spray. All treatments were given as 1 spray per nostril twice daily. The primary efficacy variable was the change from baseline in the total nasal symptom score (TNSS), consisting of nasal congestion, runny nose, itchy nose, and sneezing. Results All 3 active groups were statistically superior ( P ≤ .02) to placebo, and the combination was statistically superior ( P ≤ .003) to either agent alone. The TNSS improved by 28.4% with combination azelastine-fluticasone, 20.4% with fluticasone, 16.4% with azelastine, and 11.2% with placebo. All 3 treatments were well tolerated. Conclusions The combination azelastine-fluticasone nasal spray provided statistically significant improvement in the TNSS and additive clinical benefit compared with either agent alone in patients with moderate-to-severe seasonal allergic rhinitis. Trial Registration clinicaltrials.gov Identifier: NCT00660517.

To evaluate the efficacy of levocetirizine 5 mg once daily in reducing seasonal allergic rhinitis (SAR) symptoms in US adults.This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled adults aged 18 to 65 years with SAR symptoms in the spring in the US. After a single-blind placebo run-in period, subjects received levocetirizine 5 mg or placebo once daily over 14 days. ClinicalTrials.gov registry no.: NCT00621959.Primary efficacy variable was the Total 5-Symptom Score (T5SS). Secondary variables included Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Work Productivity and Activity Impairment-Allergy Specific (WPAI-AS) questionnaire, and Epworth Sleepiness Scale (ESS). Safety assessments were based on adverse events (AEs).The intent-to-treat population comprised 596 subjects (levocetirizine, n = 301; placebo, n = 295). Comparison of mean T5SS over the total treatment period showed a nonsignificant between-group difference (levocetirizine, 8.90 +/- 0.19; placebo, 9.04 +/- 0.19; adjusted mean difference, -0.14; p = 0.546). Levocetirizine showed numerical (mean RQLQ, WPAI-AS, ESS) and statistically superior differences (two domains within WPAI-AS) compared with placebo upon analysis of secondary efficacy variables. The incidence of treatment-emergent AEs was similar (levocetirizine, 23.9%; placebo, 24.4%). As the lack of efficacy was inconsistent with all previous levocetirizine studies, post hoc analyses were performed to assess the influence of pollen counts, geography, and other factors; however, no conclusive explanation could be identified.In this study, levocetirizine 5 mg QD was well tolerated but failed to show significant efficacy compared with placebo in a US adult population with SAR. This finding is inconsistent with all previous studies with levocetirizine and in contrast to a concurrently run, similarly designed US study. It reflects the importance of conducting duplicate studies as there is always a small but real risk of false negative results in clinical studies, irrespective of the methodologic quality.

Background The safety of fexofenadine has been examined extensively in adults and school-age children. However, the safety of fexofenadine in children younger than 6 years has not been reported to date. Objective To compare the safety and tolerability of twice-daily fexofenadine hydrochloride, 30 mg, and placebo in preschool children aged 2 to 5 years with allergic rhinitis. Methods This was a multicenter, double-blind, randomized, placebo-controlled, parallel-group study, conducted between February 29, 2000, and June 14, 2001. Participants were randomized to either fexofenadine hydrochloride, 30 mg, or placebo twice daily for a 2-week period. To facilitate dosing, capsule content was mixed with applesauce (approximately 10 mL). Safety assessments depended on date of entry into the study because of an amendment to the protocol. Before the amendment, assessments included physical examination, vital signs reporting (oral temperature, heart rate, and respiratory rate), and adverse event (AE) reporting. After the amendment, safety assessments included laboratory testing (blood chemistry and hematology profiles), physical examination, 12-lead electrocardiography, and vital signs (oral temperature, blood pressure, heart rate, and respiratory rate) and AE reporting. Results Treatment-emergent AEs were observed in 116 of 231 participants receiving placebo and 111 of 222 receiving fexofenadine. These AEs were possibly related to study medication in 19 (8.2%) and 21 (9.5%) of the participants receiving placebo and fexofenadine, respectively, and most frequently involved the digestive system. No clinically relevant differences in laboratory measures, vital signs, and physical examinations were observed. Conclusions The findings show that fexofenadine hydrochloride, 30 mg, is well tolerated and has a good safety profile in children aged 2 to 5 years with allergic rhinitis.

Influenza can cause significant morbidity and mortality in subjects at high risk for complications, including the elderly (ageor=65 years) and those with chronic respiratory, cardiovascular, or metabolic conditions. Effective prophylaxis can significantly reduce the disease burden in this population. Previous studies conducted primarily in non-high-risk subjects have reported the efficacy of inhaled zanamivir in preventing influenza.This study investigated the efficacy and safety of zanamivir in preventing influenza in community-dwelling adult and adolescent subjects at high risk for complications of influenza.This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in community-dwelling subjects agedor=12 years who were at high risk for developing complications of influenza, were able to use the Diskhaler device (Glaxo Group Limited, Research Triangle Park, North Carolina), and were able to take the first dose of study medication within 5 days of laboratory-confirmed local influenza activity. Eligible subjects were randomized to receive inhaled zanamivir 10 mg or placebo once daily for 28 days. The primary end point was the proportion of randomized subjects who developed symptomatic influenza during prophylaxis, as confirmed by culture and/or serology. All adverse events (AEs) occurring after the first dose of study medication were recorded.The study enrolled 3363 subjects, of whom 58% were female and 93% were white; the mean age of participants was 60.4 years (range, 12-94 years), and 4% were adolescents. Significantly fewer zanamivir-treated subjects developed symptomatic, laboratory- confirmed influenza during prophylaxis compared with placebo recipients (4/1678 vs 23/1685, respectively), representing a relative risk (RR) of 0.17 (95% CI, 0.07-0.44; P0.001) and a protective efficacy of 83%. The incidence of complications was reduced in zanamivir-treated subjects compared with placebo recipients (1/1678 and 8/1685), representing an RR of 0.12 (95% CI, 0.02-0.73; P = 0.042) and a protective efficacy of 88%. The numbers of zanamivir recipients (151/1678 [9%]) and placebo recipients (169/1685 [ 10 % ] ) who developed symptomatic influenza-like illness regardless of laboratory confirmation did not differ significantly (RR = 0.86; 95% CI, 0.70-1.06), indicating that zanamivir was not effective in preventing influenza-like illness that was not caused by influenza infection. Similarly, there was no significant difference in the numbers of zanamivir and placebo recipients who developed laboratory-confirmed infection regardless of symptoms (39/1678 [2%] and 52/1685 [3%], respectively; RR = 0.76; 95% CI, 0.50-1.15). Of these, 64 subjects (35 and 29) were asymptomatic; seroconversion occurred in all but 1 subject, indicating that zanamivir prophylaxis did not prevent asymptomatic seroconversion. During prophylaxis, 51% of subjects in both treatment groups reported at least 1 AE. There were no major differences in the frequency or nature of AEs between groups. The most commonly reported AEs (or=3% of subjects in each treatment group) were consistent with upper respiratory viral infection (headache: 17% zanamivir, 18% placebo; cough: 14% and 15%, respectively; throat and tonsil discomfort/pain: 13% and 14%). There were no differences between groups in the overall incidence of viral respiratory infections (5% in both groups) or ear, nose, and throat infections (2% in both groups). None of the analyzed isolates from confirmed cases of influenza exhibited reduced susceptibility to zanamivir or genotypic evidence of resistance.Zanamivir, administered once daily for 28 days, was efficacious in preventing infection with the predominant circulating strains in the 2000- 2001 influenza season in the Northern Hemisphere (influenza A/New Calendonia/20/99-1ike and influenza B/ Sichuan/379/99-like) in these high-risk community- dwelling subjects agedor=12 years. Zanamivir was well tolerated, with a safety profile comparable to that of placebo. No emergence of resistant virus was detected.

Efficacy and safety of fluticasone furoate nasal spray, administered using a unique side-actuated device, were evaluated in patients > or =12 years of age with seasonal allergic rhinitis to determine the optimal dose. A randomized, double-blind, parallel-group, placebo-controlled, dose-ranging study was performed on 641 patients who received placebo (n=128) or fluticasone furoate, 55 microg (n=127), 110 microg (n=127), 220 microg (n=129), or 440 microg (n=130), once daily for 2 weeks. Fluticasone furoate was significantly more effective than placebo for mean changes from baseline over the 2-week treatment period in daily reflective total nasal symptom score (primary end point; p < 0.001 each dose vs. placebo), morning predose instantaneous total nasal symptom score (p < 0.001 each dose versus placebo), daily reflective total ocular symptom score (p < or = 0.013 each dose versus placebo), and morning predose instantaneous total ocular symptom score (p < or = 0.019 for three highest doses versus placebo). The onset of action for fluticasone furoate nasal spray versus placebo was observed 8 hours after the first. dose of study medication in the 110 and 440 microg treatment groups (p < or = 0.032). The incidence of adverse events, results of clinical laboratory tests, and changes in 24-hour urinary cortisol values were similar between active treatment groups and placebo. The preliminary profile of fluticasone furoate is that of a rapidly effective therapy that confers 24-hour efficacy for both nasal and ocular symptoms with once-daily dosing. The 110-microg dose was chosen for phase III development because it achieved statistically significant and clinically meaningful results for all efficacy end points and provided the optimal risk-benefit ratio.

Background Allergic rhinitis (AR), an inflammatory disease of the nasal mucosa, affects approximately 25% of adults and 40% of children in the United States. Ciclesonide nasal spray is a corticosteroid being developed as a hypotonic formulation for AR. Objective We sought to evaluate the efficacy, safety, and tolerability of ciclesonide nasal spray in adult and adolescent patients with seasonal AR (SAR). Methods In this double-blind study patients (age, ≥12 years) were randomized to receive 200 μg of intranasal ciclesonide (n = 164) or placebo (n = 163) once daily for 28 days. The primary measure was morning and evening patient-assessed reflective total nasal symptom score (TNSS). Additionally, instantaneous TNSSs, physician-assessed overall nasal signs and symptoms severity, and the results of the Rhinoconjunctivitis Quality of Life Questionnaire were evaluated. Adverse events were monitored throughout the study. Results Ciclesonide significantly improved average morning and evening reflective and instantaneous TNSSs compared with placebo over days 1 to 14 ( P P P = .011). Ciclesonide was well tolerated. Conclusion Intranasal ciclesonide was superior to placebo in relieving nasal symptoms in adult and adolescent patients with SAR. These results confirm the dose range–finding study in patients with SAR and support the efficacy of ciclesonide in AR. Clinical implications In a clinical setting ciclesonide was shown to be safe and effective in the treatment of SAR in adolescent and adult patients.

Seasonal allergic rhinitis (SAR) exerts a significant adverse impact on health-related quality of life (QoL) and productivity of those who suffer from it. Unfortunately, some therapies for SAR also have a negative impact. Therefore, it is important to scrutinize the influence of new SAR therapies on patients' QoL and ability to function. The purpose of this study was to evaluate the effect of a new nasal antihistamine, olopatadine, on QoL in SAR patients. In a multicenter, randomized, double-blind SAR study comparing olopatadine 0.6 and 0.4% to placebo nasal spray, patients completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at baseline and after 2 weeks of treatment. The RQLQ is a validated questionnaire that addresses overall QoL and 7 domains of impairment associated with rhinoconjunctivitis (activities, sleep, non--nose/eye allergy symptoms, practical problems, nasal symptoms, eye symptoms, and emotional impairment). The overall RQLQ mean changes from baseline with olopatadine 0.6% (-1.1 +/- 1.4) and 0.4% (-1.1 +/- 1.3) nasal sprays were superior (p < 0.05) to placebo (-0.8 +/- 1.2). Olopatadine spray 0.6% was superior to placebo in six of the seven RQLQ domains and olopatadine 0.4% was superior to placebo in five RQLQ domains (p < 0.05). The correlation between the olopatadine 0.6% mean total symptom scores and mean RQLQ score was r = 0.66 (p < 0.0001), indicating that the enhancement in QoL derived from olopatadine therapy was significantly associated with symptom reduction. Olopatadine nasal spray is an effective antiallergy medication that significantly improves the QoL of patients suffering from SAR.

Background A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR) to mountain cedar. Objective To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo nasal spray in patients with SAR to mountain cedar. Methods This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 677 patients aged 12 to 81 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. Results Olopatadine spray (0.4% and 0.6%) was statistically significantly superior to placebo for percentage change from baseline in overall reflective and instantaneous TNSSs. Also, 0.6% olopatadine was statistically significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny nose, itchy nose, stuffy nose, itchy eyes, and watery eyes. 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 and individual symptoms, including congestion, itchy and runny nose, sneezing, and itchy and watery eyes, in patients with SAR to mountain cedar. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.

BACKGROUND: If monotherapy with an intranasal corticosteroid can alleviate both nasal and ocular symptoms of allergic rhinitis, treatment may be simplified and costs may be reduced. OBJECTIVE: The purpose of this study was to evaluate the efficacy of once-daily fluticasone propionate (FP) aqueous nasal spray 200 microg compared with vehicle placebo and oral loratadine (LOR) 10 mg in reducing ocular symptoms associated with seasonal allergic rhinitis. METHODS: A total of 471 patients received vehicle placebo, LOR, or FP in this multi-centre, double-blind, double-dummy, randomized study. Patients were > or =12 years old with a history of seasonal allergic rhinitis and a positive skin test for a relevant allergen. During the baseline and treatment periods, patients rated the severity of eye itching, tearing, and redness via visual analogue scales that ranged from 0 (no symptoms) to 100 (most severe symptoms). The three ocular ratings were added to derive the total ocular symptom score (TOSS). Patients with a TOSS > or =120 on at least 4 of the 7 days before the randomization visit were enrolled. The primary outcome was the difference between FP and vehicle placebo in the mean change from baseline in the reflective TOSS overall (averaged over the 28-day treatment period). A difference between FP and vehicle placebo of 25.5 was considered clinically significant. RESULTS: The overall mean change from baseline in the TOSS was significantly greater in the FP group compared with vehicle placebo (clinically significant difference of 28.8; P

Background Previous studies have shown that fexofenadine and cetirizine effectively relieve symptoms of seasonal allergic rhinitis (SAR). Objective To compare the effects of fexofenadine hydrochloride, 180 mg, and cetirizine, 10 mg, on symptoms, drowsiness, and motivation in patients with moderate-to-severe SAR. Methods In this 2-week multicenter, double-blind, randomized study, 495 subjects with moderate-to-severe SAR received once-daily fexofenadine hydrochloride, 180 mg, or cetirizine, 10 mg, without regard to food intake. Daily 12-hour reflective (am, pm) and instantaneous (am) individual symptoms and total symptom score (TSS) were evaluated. Drowsiness and motivation were recorded daily using visual analog scale at 7 am, 10 am, and 3 pm. Results Between-treatment differences in reduction from baseline in am instantaneous and 24-hour reflective TSS were −0.18 [95% confidence interval (CI), −0.55 to 0.20) and −0.22 (95% CI, −0.59 to 0.15), respectively. Since CIs for reduction in TSS between treatments fell within a 0.7 margin (defined a priori), treatments were considered statistically equivalent. Patients receiving fexofenadine experienced significantly less overall drowsiness vs baseline than those receiving cetirizine [−2.33 (95% CI, −3.80 to 0.86) vs 0.37 (95% CI, −1.10 to 1.84), P = .0110]. There was a trend toward greater improvements in overall motivation with fexofenadine compared with cetirizine [−2.36 (95% CI, −3.83 to 0.90) vs −0.30 (95% CI, −1.76 to 1.17), P = .0504]. Conclusions Once-daily fexofenadine hydrochloride, 180 mg, given for 2 weeks caused statistically and clinically equivalent improvement in symptoms and significantly less drowsiness va baseline, compared with cetirizine, 10 mg, in patients with moderate-to-severe SAR.

Summary Background Cysteinyl leukotrienes are important proinflammatory mediators believed to have a role in allergic rhinitis. Objective This multicentre, randomized, double-blind, placebo- and active-controlled trial evaluated the effectiveness and tolerability of montelukast, a cysteinyl leukotriene receptor antagonist, for treating patients with seasonal allergic rhinitis. Methods After a 3- to 5-day, single-blind placebo run-in period, 1302 male and female patients (aged 15–81 years) with active allergic rhinitis symptoms were randomly assigned to receive montelukast 10 mg (n = 348), loratadine 10 mg (n = 602), or placebo (n = 352) administered once daily at bedtime for 2 weeks during the spring allergy season. Results Mean patient characteristics and symptom scores at baseline were similar for the three treatment groups. The primary end-point, daytime nasal symptoms score (mean of nasal congestion, rhinorrhea, nasal pruritus, and sneezing scores; 0–3 scale), improved from baseline during treatment by (least squares mean, 95% confidence interval) − 0.37 (− 0.43, − 0.31), − 0.47 (− 0.52, − 0.43), and − 0.24 (− 0.29, − 0.18) in the montelukast, loratadine, and placebo groups, respectively (P ≤ 0.001 comparing each active treatment with placebo). Mean changes from baseline in all other diary-based scores, including night-time and eye symptom scores, were significantly greater for each active treatment than for placebo. The rhinoconjunctivitis quality of life overall score improved significantly with montelukast and with loratadine as compared with placebo. Montelukast and loratadine showed a safety profile comparable to that of placebo. Conclusion Montelukast is well tolerated and provides improvements in daytime and night-time symptoms, as well as quality of life parameters, for patients with seasonal allergic rhinitis.

This 12-week, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of budesonide 400 microg administered once daily via Turbuhaler in adults previously treated with at least twice-daily dosing of inhaled corticosteroids. Pulmonary function (FEV1, PEF, FVC, FEF(25-75%)), asthma symptom scores, quality of life, and breakthrough medication use were significantly (p < 0.05) different in patients receiving once-daily budesonide Turbuhaler compared to placebo, and significantly (p < 0.001) more patients receiving placebo discontinued the study. Adverse events were similar between study groups. Once-daily administration of budesonide Turbuhaler was safe and efficacious in patients previously treated with inhaled corticosteroids.

Background: The efficacy and safety of mometasone furoate aqueous nasal spray (MFNS; Nasonex) 200 μg once daily for the treatment and prophylaxis of seasonal allergic rhinitis (SAR) and treatment of perennial rhinitis have been demonstrated in adults. However, the dose response of MFNS in pediatric patients has not yet been characterized. Objective: This study was conducted to determine the dose-response relationship of 3 different doses of MFNS in a pediatric population. Methods: This was a multicenter, double-blind, active- and placebo-controlled study of 679 children 6 to 11 years of age with histories of SAR and documented positive skin test responses. Patients were randomized to one of the following treatment groups for 4 weeks: MFNS 25 μg once daily, MFNS 100 μg once daily, MFNS 200 μg once daily, beclomethasone dipropionate 84 μg twice daily (168 μg/day), or placebo. Physician evaluations were performed at days 4, 8, 15, and 29, and patient evaluations were analyzed for days 1 to 15 and 16 to 29. Results: The mean reduction from baseline in physician-evaluated total nasal symptom scores at day 8 (the primary efficacy variable) was significantly greater in the MFNS and beclomethasone dipropionate groups than in the placebo group ( P ≤ .02). No significant differences were observed among the 3 MFNS groups. However, as treatment continued, symptoms in patients treated with MFNS 100 or 200 μg once daily continued to improve, whereas those treated with MFNS 25 μg once daily demonstrated little further improvement. By day 29, MFNS 100 and 200 μg once daily both were significantly more effective than MFNS 25 μg once daily in relieving symptoms of SAR, but MFNS 200 μg provided no additional benefit over MFNS 100 μg. All doses of MFNS were well tolerated, and cosyntropin stimulation tests performed before and after treatment found no evidence of hypothalamic-pituitary-adrenal axis suppression. Conclusion: These results indicate that the most appropriate therapeutic dosage of MFNS in the treatment of SAR in children 6 to 11 years of age is 100 μg once daily. In addition, MFNS at doses up to 200 μg once daily for 4 weeks was well tolerated and had no detectable effects on hypothalamic-pituitary-adrenal axis function. (J Allergy Clin Immunol 1999;104:107-14.)

This multicenter, double-blind, placebo-controlled trial evaluated the efficacy and safety of levocabastine nasal spray, a potent and selective H1-receptor antagonist, in the control of histamine-mediated symptoms of seasonal allergic rhinitis. Adults with ≥2 year history of allergic rhinitis due to Mountain Cedar were randomized to treatment with levocabastine nasal spray (0.2 mg twice daily) or placebo for 28 days during the 1994–1995 Mountain Cedar allergy season. Patients assessed the severity of their rhinitis symptoms on a four-point scale twice daily. At the end of the trial, patients also performed a global evaluation of treatment efficacy on a five-point scale. Overall for the 4-week treatment period, levocabastine nasal spray significantly reduced major nasal (runny nose and sneezing) and primary rhinitis (runny nose, sneezing, and itchy/gritty eyes) symptoms compared with placebo on both repeated measures (p = 0.023; p = 0.01) and ANOVA (p = 0.003; p < 0.001) analyses. Global evaluations of treatment efficacy at the end of the trial significantly favored levocabastine over placebo (p = 0.002). Overall, the incidence of adverse events was similar for both treatment groups. In general, most adverse events were mild in intensity, with sinusitis (17% each group), headache (17% placebo, 14% levocabastine), and rhinitis (8% placebo, 2% levocabastine) most commonly reported. Levocabastine nasal spray 0.2 mg twice daily was significantly more effective than placebo in the relief of histamine-mediated symptoms in patients with seasonal allergic rhinitis and was well tolerated over the 28-day treatment period.

Previous trials demonstrated the effectiveness of the leukotriene receptor antagonist zafirlukast in patients with mild-to-moderate asthma.We sought to assess the efficacy and safety of zafirlukast and its effect on patients' quality of life (QOL) during a 13-week, double-blind, placebo-controlled, multicenter trial in adults and adolescents with moderate reversible airflow obstruction.Patients (age range, 12 to 68 years) with total daytime asthma symptoms scores of 10 or greater over 7 consecutive days (maximum, 21/wk), FEV1 45% or greater but less than or equal to 80% of predicted value (/=6 hours after beta2 -agonist), and reversible airway disease were randomized to 20 mg zafirlukast twice daily (nZ = 231) or placebo twice daily (nP = 223). Efficacy was assessed from changes in daytime and nocturnal symptoms, beta2 -agonist use, nasal congestion score, and pulmonary function. QOL was evaluated with a disease-specific Asthma Quality of Life Questionnaire. Safety was determined from adverse event information and clinical laboratory test results.Zafirlukast was significantly (P.001) more effective than placebo, with reductions from baseline in the daytime asthma symptoms score (-23%), nighttime awakenings with asthma (-19%), and beta2 -agonist use (-24%) and improvements from baseline in morning (+25 L/min) and evening (+18 L/min) peak expiratory flow rates. Compared with placebo, zafirlukast significantly (P/=.018) improved scores for QOL domains (activity limitations, symptoms, emotional function, and exposure to environmental stimuli) and overall QOL, with a significantly greater proportion of zafirlukast-treated patients demonstrating clinically meaningful improvements (/=0.5-unit change from baseline; P/=.037). The safety profile of zafirlukast was clinically indistinguishable from that of placebo.Zafirlukast is effective and well tolerated and improves QOL in the long-term treatment of patients with moderate reversible airflow obstruction.

To study the long-term safety and effectiveness of ipratropium bromide nasal spray 0.03% in the treatment of nonallergic perennial rhinitis, we administered this medication for 1 year in an open-label trial involving 285 patients. Our intention was to maintain the highest protocol dose possible to gain a clearer picture of the long-term side effect profile of the compound. Ipratropium bromide was well tolerated with no serious side effects in this patient population. It provided a significant improvement in rhinorrhea throughout the year-long trial; only 17 of 285 patients (6%) were considered treatment failures. There was an improvement in patient quality of life, as well as a substantial reduction in the need for other medications (antihistamines, decongestants, and nasal steroids) used to treat perennial rhinitis symptoms.

Background Intranasal corticosteroids are effective in controlling allergic rhinitis (AR) symptoms; however, chronic administration of corticosteroids may suppress hypothalamic-pituitary-adrenal (HPA)-axis function. Objective To evaluate the effects of 6 weeks of treatment with beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol on HPA-axis function in subjects with perennial AR (PAR). Methods In this randomized, double-blind, placebo- and active-controlled study, subjects aged 12 to 45 years were randomized to receive BDP nasal aerosol 320 μg/day ( n = 50), placebo ( n = 46), or placebo/prednisone (prednisone 10 mg/day for the last 7 days of the treatment period [ n = 11]). The primary end point was change from baseline in 24-hour serum cortisol (SC) weighted mean (expressed as geometric mean ratio [GMR]) in the BDP and placebo group after 6 weeks of treatment. Results Geometric SC-weighted mean values were similar in the BDP and placebo groups at baseline (9.04 and 8.45 μg/dL, respectively) and after 6 weeks (8.18 and 8.01 μg/dL, respectively). After 6 weeks of treatment, BDP was noninferior to placebo with respect to the ratio from baseline in SC-weighted mean (GMR: 0.96 [95% CI: 0.87, 1.06]). In contrast, 7 days of prednisone treatment substantially reduced geometric SC-weighted mean values from baseline (approximate 3-fold reduction [from 7.33 to 2.31 μg/dL]) compared with placebo. BDP nasal aerosol was well tolerated, and the safety profile was similar to that of placebo. Conclusion Treatment with BDP nasal aerosol, 320 μg once daily, was not associated with HPA-axis suppression in adolescent and adult subjects with PAR. Trial Registration Clinicaltrials.gov Identifier: NCT01133626.

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 ⩽ 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.

Allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) are common causes of substantial illness and disability in preschool children. Antihistamines are commonly used to treat preschool children with these conditions, but their use is based mostly on extrapolated efficacy from adult populations; it is thus important to characterize the safety of antihistamines in the pediatric population. This study was designed to assess the safety of levocetirizine dihydrochloride oral liquid drops in infants and children with AR or CIU. Two multicenter, double-blind, randomized, parallel-group studies randomized infants aged 6-11 months (study 1, n = 69) and children aged 1-5 years (study 2, n = 173) to levocetirizine, 1.25 mg (q.d. or b.i.d., respectively), or placebo for 2 weeks, using a 2:1 ratio. Safety evaluations included treatment-emergent adverse events (TEAEs), vital signs, electrocardiographic (ECG) assessments, and laboratory tests. The overall incidence of TEAEs was similar between levocetirizine and placebo in both studies. Most TEAEs were mild or moderate in intensity. TEAEs prompted discontinuation of therapy in three patients receiving levocetirizine in study 1. No clinically relevant changes from baseline in vital signs or laboratory parameters were apparent in either study; changes from baseline in these evaluations were similar between groups. No significant changes were observed in ECG parameters, including corrected QT interval. Levocetirizine, 1.25 and 2.5 mg/day, was well tolerated in infants aged 6-11 months and in children aged 1-5 years, respectively, with AR or CIU.

Fluticasone propionate was compared with beclomethasone dipropionate for the treatment of allergic rhinitis in a multicenter, double-blind, randomized, placebo-controlled study during the mountain cedar (Juniperus ashei) pollination season in central Texas. Adults (n = 313) with moderate to severe symptoms were treated with fluticasone propionate aqueous nasal spray 200 micrograms once a day or beclomethasone dipropionate aqueous nasal spray 168 micrograms twice a day or placebo for 2 weeks. Fluticasone propionate administered once daily and beclomethasone dipropionate administered twice daily were equally effective as assessed by clinician- and patient-rated scores for nasal obstruction, rhinorrhea, sneezing, and nasal itching throughout the treatment and follow-up periods. Both regimens were more effective than placebo. Adverse events were related to topical administration and were similar in frequency and nature in all three treatment groups. Fluticasone propionate and beclomethasone dipropionate displayed a similar safety profile that did not differ from placebo. We conclude that fluticasone propionate aqueous nasal spray administered as 200 micrograms once daily in the morning is as safe and effective as beclomethasone dipropionate aqueous nasal spray administered as 168 micrograms twice daily for seasonal allergic rhinitis.

To our knowledge, there are no published studies that evaluated the efficacy of azelastine hydrochloride nasal spray in combination with an intranasal corticosteroid, although anecdotal reports of the use of these agents in combination are common.To determine if greater efficacy could be achieved with the intranasal antihistamine azelastine and the intranasal corticosteroid fluticasone propionate used concurrently compared with the efficacy of each agent alone.This randomized, 2-week, multicenter, double-blind trial was conducted during the Texas mountain cedar season. After a 5-day placebo lead-in period, 151 patients with moderate to severe nasal symptoms were randomized to treatment with the following: (1) azelastine nasal spray, 2 sprays per nostril twice daily; (2) fluticasone nasal spray, 2 sprays per nostril once daily; or (3) azelastine nasal spray, 2 sprays per nostril twice daily, plus fluticasone nasal spray, 2 sprays per nostril once daily. The primary efficacy variable was the change from baseline in the total nasal symptom score (TNSS), consisting of sneezing, itchy nose, runny nose, and nasal congestion.All 3 groups had statistically significant (P.001) improvements from their baseline TNSS after 2 weeks of treatment. The TNSS improved 27.1% with fluticasone nasal spray, 24.8% with azelastine nasal spray, and 37.9% with the 2 agents in combination (P.05 vs either agent alone). All 3 treatments were well tolerated.The significant improvement in the TNSS with combination therapy relative to the individual agents alone is in contrast to previously published studies that found no advantage with an oral antihistamine and an intranasal corticosteroid in combination. Azelastine nasal spray and fluticasone nasal spray in combination may provide a substantial therapeutic benefit for patients with seasonal allergic rhinitis compared with therapy with either agent alone.

Background Antihistamines are an established first-line treatment for allergic rhinitis and are widely prescribed in infants for allergic symptoms. Objective To establish the safety and tolerability of fexofenadine hydrochloride in children aged 6 months to 2 years in 2 studies (T/3001 and T/3002). Methods Both studies had a multicenter, randomized, placebo-controlled design. Mean treatment duration was 8 days. Subjects were randomized (T/3001, n = 174; and T/3002, n = 219) to twice-daily fexofenadine hydrochloride, 15 or 30 mg, or placebo mixed with a standard vehicle. Results In the combined population, the incidence of treatment-emergent adverse events (TEAEs) was comparable between groups (placebo, 48.2% [96/199]; fexofenadine hydrochloride, 15 mg, 40.0% [34/85]; and fexofenadine hydrochloride, 30 mg, 35.2% [38/108]). Vomiting was the most common TEAE (placebo, 13.6%; fexofenadine hydrochloride, 15 mg, 14.1%; and fexofenadine hydrochloride, 30 mg, 5.6%). Most TEAEs were unrelated to study medication, as evaluated by investigators; those possibly related to study medication were mild or moderate in intensity. No clinical differences were seen between fexofenadine and placebo for vital signs, electrocardiographic results, or physical examination results. Conclusion Fexofenadine hydrochloride, 15 or 30 mg, given for a mean duration of 8 days is well tolerated, with a good safety profile, in children aged 6 months to 2 years.

Background Ciclesonide is an investigational corticosteroid under development for treatment of allergic rhinitis. Ciclesonide is converted to active metabolite, desisobutyryl-ciclesonide (des-CIC), by upper and lower airway esterases. In vitro studies in human nasal epithelial cells and bronchial epithelial cells have demonstrated a long duration of anti-inflammatory activity of des-CIC. Objective To evaluate the dose-dependent efficacy and safety of a hypotonic intranasal formulation of ciclesonide in patients with seasonal allergic rhinitis (SAR). Methods This was a phase 2, randomized, parallel-group, double-blind, placebo-controlled study. Adults (n = approximately 145 per treatment group) with a minimum 2-year history of SAR received placebo or ciclesonide (25, 50, 100, or 200 μg/d) for 14 days. The primary end point was change in the sum of morning and evening reflective total nasal symptom scores (TNSSs) over 2 weeks. Safety was monitored throughout the study. Results Ciclesonide, 100 μg/d ( P = .04) and 200 μg/d ( P = .003), significantly improved the sum of morning and evening reflective TNSS vs placebo at more than 2 weeks of treatment. Baseline values for morning and evening reflective TNSS ranged from 17.80 to 18.82 across treatment groups. The average change from baseline in reflective TNSS was −4.2 for placebo and −4.8, −4.8, −5.3, and −5.8 for ciclesonide, 25, 50, 100, and 200 μg/d, respectively. There were no dose-related differences in the incidence of adverse events among treatment groups. Conclusions Results from this study indicate that 100-μg and 200-μg daily doses of ciclesonide are effective in the treatment of SAR. Ciclesonide, 200 μg/d, appears to be the optimal dose studied for reducing the symptoms of SAR while maintaining an acceptable safety profile.

In fall 2004, the first Azelastine Cetirizine Trial demonstrated statistically significant improvements in the total nasal symptom score (TNSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores with the use of azelastine nasal spray vs oral cetirizine in patients with seasonal allergic rhinitis (SAR).To compare the effects of azelastine nasal spray vs cetirizine on the TNSS and RQLQ scores in patients with SAR.This 2-week, double-blind, multicenter trial randomized 360 patients with moderate-to-severe SAR to azelastine, 2 sprays per nostril twice daily, or cetirizine, 10-mg tablets once daily. The primary efficacy variable was the 12-hour reflective TNSS (rhinorrhea, sneezing, itchy nose, and nasal congestion). Secondary efficacy variables were individual symptom scores and the RQLQ score.Azelastine nasal spray and cetirizine significantly improved the TNSS and individual symptoms compared with baseline (P.001). The TNSS improved by a mean of 4.6 (23.9%) with azelastine nasal spray compared with 3.9 (19.6%) with cetirizine. Significant differences favoring azelastine nasal spray were seen for the individual symptoms of sneezing and nasal congestion. Improvements in the RQLQ overall (P = .002) and individual domain (Por = .02) scores were greater with azelastine nasal spray. Both treatments were well tolerated.Azelastine nasal spray and cetirizine effectively treated nasal symptoms in patients with SAR. Improvements in the TNSS and individual symptoms favored azelastine over cetirizine, with significant differences for nasal congestion and sneezing. Azelastine nasal spray significantly improved the RQLQ overall and domain scores compared with cetirizine.

Few studies have directly compared the efficacy of intranasal corticosteroids with that of leukotriene receptor antagonists for the treatment of daytime and nighttime symptoms of seasonal allergic rhinitis (SAR).To compare fluticasone propionate aqueous nasal spray, 200 microg daily, with oral montelukast, 10 mg daily, for the relief of SAR symptoms.Patients with SAR 15 years or older were randomized to receive either fluticasone propionate (n = 367) or montelukast (n = 369) in this double-blind, double-dummy, parallel-group study. The primary efficacy measure was the mean change from baseline in daytime total nasal symptom scores (TNSSs) (the sum of 4 daytime individual nasal symptom scores [INSSs] assessing nasal congestion, itching, rhinorrhea, and sneezing), averaged across weeks 1 and 2. Secondary efficacy measures included the 4 daytime INSSs, nighttime TNSSs (the sum of 3 nighttime INSSs assessing congestion on awakening, difficulty going to sleep, and nighttime awakenings), and the 3 nighttime INSSs averaged across weeks 1 and 2.Mean changes from baseline in daytime TNSSs (P.001), all daytime INSSs (P.001), nighttime TNSSs (P.001), and all nighttime INSSs (Por = .02) showed significant differences favoring fluticasone propionate over montelukast across 2 weeks of treatment.Compared with montelukast, fluticasone propionate provided significantly greater improvement in daytime and nighttime SAR symptoms.

A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR).To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo in patients with SAR.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).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.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.

Montelukast has shown efficacy for seasonal allergic rhinitis (SAR); however, onset of action for SAR has not been presented. The aim of this study was to determine the onset of action of montelukast, 10 mg, measured in days after starting once-daily therapy, in spring and fall studies of SAR. Data were analyzed from four 2-week, double-blind, placebo-controlled phase III clinical trials. End points included the daytime nasal symptoms score, the nighttime symptoms score, the composite symptoms score (mean of the scores for daytime nasal symptoms and nighttime symptoms), and the daytime eye symptoms score. Using a 0-3 scale (no symptoms to severe symptoms), daytime symptoms were rated by patients once daily each evening; nighttime symptoms were rated once daily each morning. Analyses of data pooled across the four evening dosing studies showed that montelukast, compared with placebo, produced significant improvement (por = 0.001) from baseline by day 2 of treatment (after 2 doses) in the daytime nasal symptoms score, nighttime symptoms score, and composite symptoms score. Differences between montelukast and placebo for these end points in mean change from baseline at day 2 were -0.08 (95% CI, -0.12, -0.03), -0.08 (95% CI, -0.13, -0.04), and -0.08 (95% CI, -0.12, -0.04), respectively. These data represented a mean reduction for montelukast of 11-13% in symptom scores from baseline for each end point at day 2. When compared with the full 2-week response, these observed differences for each end point at day 2 (after 2 doses) represented a substantial proportion (over 70%) of the overall treatment benefits seen. Significant improvement (por = 0.001) in the daytime eye symptoms score was seen by day 1 (-0.08 [-0.12, -0.03]), after the first dose. In patients treated for SAR, montelukast has a beneficial effect on daytime and nighttime symptoms by the 2nd day of daily therapy.

In the treatment of asthma, the conventional measures used to monitor a patient's progress and health status do not address the impact of functional impairments associated with the disease that may affect the patient's daily life. Unlike those measures, health-related quality of life (HRQL) reflects the physical, psychological, and social difficulties a patient perceives on a day-to-day basis. This study was conducted to determine the effects of once-daily budesonide inhalation powder via the Pulmicort Turbuhaler on the HRQL in adult patients with asthma previously treated with other inhaled corticosteroids. A total of 184 patients 18 to 70 years of age who previously received inhaled corticosteroids were enrolled in this double-blind, placebo-controlled, parallel-group, multicenter study. Patients were randomly assigned to budesonide 400 microg once daily or to placebo for 12 weeks. Each patient's HRQL was assessed at randomization and at weeks 4 and 12 with the Asthma Quality of Life Questionnaire (AQLQ). More patients receiving budesonide than those receiving placebo reported statistically significant (Por = .05) improvements in HRQL at weeks 4 and 12. With the exception of the domain pertaining to exposure to environmental stimuli, differences from placebo in overall AQLQ scores and individual domain scores were clinically important (or = 0.5 units). In addition, 2.4 patients needed to be treated with once-daily budesonide for 1 patient to demonstrate clinically important improvement. Budesonide 400 microg administered once daily via the Pulmicort Turbuhaler provides statistically significant and clinically important HRQL benefit in adult patients with asthma previously receiving inhaled corticosteroids.

Background: Few randomized studies have compared loratadine to ebastine in the symptomatic treatment of seasonal allergic rhinitis (SAR) patients. Methods: This double-blind, placebo-controlled, randomized, parallel-group, comparative trial compared the efficacy and safety of ebastine 20 mg (E20), loratadine 10 mg (L10) and placebo (P), administered once daily, in the control of SAR symptoms over a 2-week period. An additional 2-week treatment period was included in order to check sustained efficacy and tolerability. Results: A total of 703 patients were enrolled: 282 patients in the E20 group, 279 in the L10 group and 142 in the P group. E20 showed a greater decrease from baseline in the main efficacy variable (mean daily reflective total symptom score) than L10 (p = 0.0018) or P (p = 0.0024), whereas the difference between L10 and P was not significant. Moreover, reductions from baseline in all composite/individual daily reflective rhinitis symptom scores were significantly larger in patients receiving E20 than in patients receiving L10 or P. Most significant differences between E20 and L10 or P were maintained after 4 weeks of treatment. Overall, all treatments were safe and well tolerated. There was no significant difference in the percentage of patients who reported one or more adverse events (AEs) between the groups, and most AEs were mild to moderate (89.9%). Conclusions: E20 given once daily for 2 weeks was more effective in the treatment of SAR symptoms than L10 or P. E20 also showed a sustained efficacy after 4 weeks of treatment, and overall was well tolerated and proved safe.

This was a double-blind, randomized, placebo-controlled, multicenter, parallel study comparing the effectiveness, at recommended doses, of an extended-release formulation of brompheniramine maleate and terfenadine in the treatment of allergic rhinitis. Subjects with symptoms of seasonal and/or perennial allergic rhinitis received brompheniramine 12 mg (n = 106), 8 mg (n = 105), terfenadine 60 mg (n = 106), or placebo (n = 53) twice daily for 14 days. On treatment days 3, 7, and 14, symptom severity ratings (i.e., rhinorrhea, sneezing, nasal congestion, itchy nose, eyes or throat, excessive tearing, postnasal drip) were completed by the physician; subjects and physicians each completed a global efficacy evaluation. Brompheniramine 12 mg and 8 mg and terfenadine were more effective than placebo (p ≤ 0.05) on the physicians’ global; brompheniramine 12 mg was more effective than terfenadine (p ≤ 0.05) on days 7 and 14 and brompheniramine 8 mg on day 3. On the subjects’ global evaluation, brompheniramine 12 mg and 8 mg and terfenadine were more effective than placebo (p ≤ 0.05); brompheniramine 12 mg was more effective than terfenadine (p ≤ 0.05) on days 7 and 14 and brompheniramine 8 mg on day 3. In general, brompheniramine 8 mg was comparable to terfenadine. On days 3 and 7, the total symptom and total nasal symptom severity scores for subjects receiving brompheniramine 12 mg were significantly more improved than for placebo (p < 0.05); terfenadine was not different from placebo; brompheniramine 12 mg was significantly better than terfenadine on day 7 (p < 0.05) for reducing total symptom severity and on days 3, 7, and 14 for reducing total nasal symptom severity. Adverse experiences were reported by 155 (41.9%) of the 370 subjects enrolled in the study. The overall rate of adverse experiences in the brompheniramine 12 mg treatment group (57.5%) was significantly greater (p < 0.05) than for brompheniramine 8 mg (38.1%), terfenadine (31.1%), and placebo (39.6%). In conclusion, an extended-release formulation of brompheniramine 12 mg or 8 mg bid alleviates allergic rhinitis symptoms and brompheniramine 12 mg provides significantly better relief of these symptoms than terfenadine 60 mg bid.

Topical nasal corticosteroids are rapidly gaining acceptance as first-line therapy for seasonal allergic rhinitis, but there is a desire for effective corticosteroids with an improved safety profile over existing products.A multicenter, double-blind dose ranging study was conducted to compare the activity and tolerance of four doses of mometasone furoate nasal spray (tradename Nasonex) and placebo in adult patients with seasonal allergic rhinitis.Four hundred eighty patients with seasonal allergic rhinitis were enrolled and randomized to receive mometasone furoate nasal spray 50 micrograms (n = 96), 100 micrograms (n = 95), 200 micrograms (n = 98) or 800 micrograms (n = 95), or placebo vehicle (n = 95) once daily for 28 days.All of the doses of mometasone furoate nasal spray showed activity in reducing the severity of rhinitis. The 200-microgram dose reduced total nasal symptom scores and total symptom scores throughout the study (P.05 versus placebo vehicle). The 50-microgram dose and the 100-microgram dose showed less consistent activity at early timepoints (days 3 and 7), while the 800 microgram dose did not provide significant additional benefits over the 200-microgram dose. All dose levels were well toleratedThe results of this trial indicate that 200 micrograms once daily is the optimum dose of mometasone furoate nasal spray for the treatment of seasonal allergic rhinitis.