Efficacy and safety of twice-daily and once-daily olopatadine-mometasone combination nasal spray for seasonal allergic rhinitis.

BACKGROUND: GSP301 is an investigational fixed-dose combination nasal spray of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). OBJECTIVE: To evaluate efficacy and safety of GSP301 in patients with seasonal AR (SAR). METHODS: In this phase 2, double-blind, parallel-group study, patients (≥12 years of age) with SAR were equally randomized to twice-daily GSP301 (olopatadine 665 µg and mometasone 25 µg), once-daily GSP301 (olopatadine 665 µg and mometasone 50 µg), twice-daily or once-daily olopatadine monotherapy (665 µg), mometasone monotherapy (twice-daily 25 µg or once-daily 50 µg), or placebo for 14 days. The primary endpoint-mean change from baseline in morning and evening reflective Total Nasal Symptom Score (rTNSS)-was analyzed using analysis of covariance (ANCOVA; P < .05 = statistically significant). Average morning and evening 12-hour instantaneous TNSS (iTNSS), ocular symptoms, individual symptoms, onset of action, quality of life, and adverse events (AEs) were also assessed. RESULTS: A total of 1111 patients were randomized. Twice-daily GSP301 provided statistically significant and clinically meaningful rTNSS improvements vs placebo (P < .001), twice-daily olopatadine (P = .049), and mometasone (P = .004). Similar significant improvements in iTNSS were observed with twice-daily GSP301 vs placebo (P < .001) and twice-daily mometasone (P = .007); improvements were not significant vs olopatadine (P = .058). Once-daily GSP301 provided significant rTNSS and iTNSS improvements vs placebo and once-daily olopatadine (P < .01, all) but improvements were not significant vs mometasone. Treatment-emergent AEs rates were 10.8%, 9.5%, and 8.2%, with twice-daily GSP301, once-daily GSP301, and placebo, respectively. CONCLUSION: Twice-daily GSP301 treatment was efficacious and well tolerated, providing statistically significant and clinically meaningful improvements in rTNSS (primary endpoint) vs placebo and both monotherapies. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT02318303.

Effect of olopatadine-mometasone combination nasal spray on seasonal allergic rhinitis symptoms in an environmental exposure chamber study.

BACKGROUND: GSP301 nasal spray is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate intended for seasonal allergic rhinitis (SAR) treatment. OBJECTIVE: To evaluate the efficacy and safety of once-daily or twice-daily GSP301 in a ragweed pollen environmental exposure chamber. METHODS: In this randomized, double-blind, double-dummy study, adults (18-65 years old) with SAR were equally randomized to 665 µg of olopatadine and 25 µg of mometasone (twice-daily GSP301), 665 µg of olopatadine and 50 µg of mometasone (once-daily GSP301), a US Food and Drug Administration-approved formulation of 137 µg of azelastine and 50 µg of fluticasone twice-daily (AzeFlu), a US Food and Drug Administration-approved formulation of 665 µg of olopatadine twice-daily, or placebo (twice-daily). During 2 visits (baseline and end of 14-day treatment), participants assessed SAR symptoms at specified time points. The primary end point-mean change from baseline in instantaneous total nasal symptom score (iTNSS) for twice-daily or once-daily GSP301 vs placebo-was analyzed by analysis of covariance. Onset of action, ocular symptoms, and adverse events were assessed. RESULTS: A total of 180 participants were randomized. Treatment with twice-daily or once-daily GSP301 provided statistically significant improvements in iTNSS vs placebo (twice-daily GSP301: least squares mean difference, -3.60; 95% confidence interval [CI], -4.89 to -2.30; once-daily GSP301: least squares mean difference, -3.05; 95% CI, -4.35 to -1.76; P < .0001 for both). Significant improvements in iTNSS with twice-daily GSP301 occurred by 10 minutes after dosing (-1.26; 95% CI, -2.30 to -0.21; P = .02) and were maintained at all later time points except one (2.5 hours). Treatment-emergent adverse events occurred in 22.2%, 30.6%, 25.0%, 22.2%, and 16.7% of participants in the twice-daily GSP301, once-daily GSP301, AzeFlu, olopatadine, and placebo groups, respectively. CONCLUSION: In an environmental exposure chamber model, twice-daily and once-daily GSP301 treatments were well tolerated and provided statistically significant and clinically meaningful SAR symptom improvement vs placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03444506.

Efficacy and safety of olopatadine-mometasone combination nasal spray for the treatment of seasonal allergic rhinitis.

BACKGROUND: GSP301 nasal spray is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). OBJECTIVE: To evaluate the efficacy and safety of GSP301 in patients with seasonal allergic rhinitis (SAR). METHODS: In this double-blind study, eligible patients (≥12 years of age) with SAR were randomized 1:1:1:1 to twice-daily GSP301 (665 µg of olopatadine and 25 µg of mometasone), olopatadine (665 µg), mometasone (25 µg), or placebo for 14 days. The primary end point-mean change from baseline in average morning and evening 12-hour reflective Total Nasal Symptom Score (rTNSS)-was analyzed via a mixed-effect model repeated measures (P < .05 was considered to be statistically significant). Additional assessments included average morning and evening 12-hour instantaneous TNSS (iTNSS), ocular symptoms, individual symptoms, onset of action, quality of life, and adverse events (AEs). RESULTS: A total of 1176 patients were randomized. GSP301 provided statistically significant and clinically meaningful rTNSS improvements vs placebo (least squares mean difference, -1.09; 95% CI, -1.49 to -0.69; P < .001) and vs olopatadine (P = .03) and mometasone (P = .02). Similar significant improvements in iTNSS were also observed with GSP301 (P < .05 for all). Furthermore, GSP301 significantly improved overall ocular symptoms, individual nasal and ocular symptoms, and quality of life vs placebo (P ≤ .001 for all). Onset of action for GSP301 was observed within 15 minutes and was maintained at all subsequent timepoints. Treatment-emergent AEs occurred in 15.6%, 12.6%, 9.6%, and 9.5% of patients in the GSP301, olopatadine, mometasone, and placebo groups, respectively. CONCLUSION: GSP301 is efficacious and well tolerated vs placebo for treating SAR-associated nasal and ocular symptoms, with a rapid onset of action of 15 minutes in adult and adolescent patients 12 years and older. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02870205.

Olopatadine-mometasone combination nasal spray: Evaluation of efficacy and safety in patients with seasonal allergic rhinitis.

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 < 0.05 indicates statistical significance). Additional assessments included instantaneous TNSS (iTNSS), individual nasal symptoms, reflective Total Ocular Symptom Score (rTOSS) and instantaneous Total Ocular Symptom Score (iTOSS), onset of action, Physician-assessed Nasal Symptom Score (PNSS), quality of life, and adverse events (AE). Results: A total of 1180 patients were randomized. Over 14 days of treatment, GSP301 significantly improved average A.M. and P.M. rTNSS versus placebo (least squares mean difference -0.98 [95% confidence interval, -1.38 to -0.57]; p < 0.001) and versus olopatadine (p = 0.003), and approached statistical significance versus mometasone (p = 0.059). GSP301 also significantly improved average A.M. and P.M. iTNSS versus placebo and both monotherapies (p < 0.05, all). Further, GSP301 significantly improved individual nasal symptoms, overall ocular symptoms (rTOSS and iTOSS), and overall quality of life versus placebo (p < 0.01, all). Onset of action for GSP301 was observed within 15 minutes and was maintained at all subsequent time points assessed. Results for the PNSS also were significant for GSP301 versus placebo (p < 0.001). The percentages of patients with treatment-emergent AEs treated with GSP301, olopatadine, mometasone, and placebo were 12.9, 12.5, 7.1, and 9.4%, respectively. Conclusion: GSP301 was efficacious and well tolerated for the treatment of SAR symptoms compared with placebo, with a rapid onset of action of 15 minutes in patients ≥12 years of age.Clinical trial NCT02631551, www.clinicaltrials.gov.

Long-term safety and efficacy of olopatadine-mometasone combination nasal spray in patients with perennial allergic rhinitis.

Background: Safety and efficacy of GSP301 nasal spray, an investigational fixed-dose combination of olopatadine hydrochloride and mometasone furoate, was established in three large, 2-week seasonal allergic rhinitis studies. Objective: To evaluate long-term (52 weeks) safety and efficacy of GSP301 in patients with perennial allergic rhinitis (PAR). Methods: In this randomized, double-blind, parallel-group study, 601 patients (ages ≥ 12 years) with PAR were randomized 4:1:1 to twice-daily GSP301 (olopatadine 665 µg and mometasone 25 µg [pH 3.7]) or two GSP301 vehicle formulations (placebo pH 3.7 or 7.0). Safety (primary end point) was monitored through adverse events (AE), laboratory assessments, vital signs, and physical examinations at weeks 30 and 52. The change from baseline in the average A.M. reflective Total Nasal Symptom Score (rTNSS) and instantaneous Total Nasal Symptom Score (iTNSS), Physician-assessed Nasal Symptom Scores (PNSS), and quality of life were assessed for GSP301 versus placebo pH 3.7 (p < 0.05 was considered statistically significant). Results: At week 52, treatment-emergent AEs (TEAE) occurred in 51.7, 41.4, and 53.5% of patients in the GSP301, placebo pH 3.7 and placebo 7.0 groups, respectively. No clinically meaningful differences were observed in TEAE incidences or other safety assessments across treatments. At weeks 6 and 30, GSP301 provided significant and clinically meaningful improvements in average rTNSS and iTNSS versus placebo pH 3.7 (p < 0.01, all comparisons). Similarly, at week 52, GSP301 provided significant and clinically meaningful improvements in rTNSS (least-squares mean difference -0.91 [95% confidence interval {CI}, -1.35 to -0.47]; p < 0.001), and iTNSS (least-squares mean difference -0.75 [95% CI, -1.17 to -0.33]; p < 0.001) versus placebo pH 3.7, with significant improvements in each individual symptom (p < 0.05, all comparisons). PNSS and quality of life were significantly improved versus placebo pH 3.7 at weeks 6 and 30 (p < 0.05, all comparisons), but these greater improvements did not reach statistical significance at week 52 (PNSS, p = 0.552; quality of life, p = 0.790). Conclusion: Twice-daily GSP301 was well tolerated and provided statistically significant and clinically meaningful improvements in PAR nasal symptoms versus placebo over 52 weeks and demonstrated a favorable safety profile and efficacy.Clinical trial NCT02709538, www.clinicaltrials.gov.

Pharmacokinetics of intranasal mometasone in the fixed-dose combination GSP301 versus two monotherapy intranasal mometasone formulations.

BACKGROUND: GSP301 is a fixed-dose combination (FDC) of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate developed as a single nasal spray (NS). OBJECTIVE: To assess the relative bioavailability of mometasone administered as GSP301 FDC versus two mometasone monotherapy NS formulations. METHODS: In this single-dose, open-label, crossover study, healthy adults (age range, 18-65 years) were randomized equally to one of six treatment sequences for three 72-hour treatment periods with GSP301 (olopatadine 665 µg-mometasone 50 µg), the mometasone furoate monotherapy component of GSP301 (MF-sponsor, 50 µg), and U.S. Food and Drug Administration-approved mometasone (MF, 50 µg); all the treatments were administered as two sprays per nostril. To evaluate the relative bioavailability of mometasone, pharmacokinetic (PK) estimates, the maximum plasma concentration (Cmax), the area under the plasma concentration time curve (AUC) from time 0 to the last time point with measurable concentration (AUC0-t), and AUC from time 0 to time infinity (AUC0-∞) were compared by analysis of variance. Safety and tolerability were also assessed. RESULTS: A total of 30 healthy subjects were randomized. Most subjects were white men who were not obese, mean age of ∼43 years. The geometric mean ratios for natural log transformed Cmax, AUC0-t, and AUC0-∞ of mometasone in GSP301 to MF-sponsor were 113.83, 118.36, and 118.50, respectively. For GSP301 and MF, geometric mean ratios for Cmax, AUC0-t, and AUC0-∞ were 141.84, 109.92, and 115.14, respectively. The percentages of subjects who reported treatment-emergent adverse events (TEAE) were 10.0%, 13.3%, and 10.3% for GSP301, MF-sponsor, and MF treatments, respectively. All TEAEs were mild, and none resulted in discontinuation. CONCLUSION: Mometasone bioavailability with GSP301 was comparable with MF-sponsor and MF monotherapies. A slightly higher Cmax was observed with GSP301 than with MF, but AUC was comparable. The addition of olopatadine to mometasone in GSP301 did not considerably affect the PK of mometasone. GSP301 was well tolerated, with only mild adverse events reported.

Pharmacokinetics of intranasal olopatadine in the fixed-dose combination GSP301 versus two monotherapy intranasal olopatadine formulations.

BACKGROUND: GSP301 is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate developed as a single nasal spray. OBJECTIVE: To assess the relative bioavailability of olopatadine administered as GSP301 versus two olopatadine monotherapy nasal spray formulations. METHODS: In this single-dose, open-label, crossover study, healthy adults (18-65 years old) were equally randomized to one of six treatment sequences for three 48-hour treatment periods with GSP301 (olopatadine 665 µg-mometasone 50 µg), the olopatadine monotherapy component of GSP301 (OLO-sponsor; 665 µg) and U.S. Food and Drug Administration approved olopatadine (OLO; 665 µg); each treatment was administered as a single dose (two sprays in each nostril). To assess the relative bioavailability of olopatadine in the fixed-dose nasal spray versus two monotherapies, pharmacokinetic (PK) estimates, maximum plasma concentration (Cmax), area under the plasma concentration time curve (AUC) from time 0 to the last time point with measurable concentration (AUC0-t), and AUC from time 0 to time infinity (AUC0-∞) were compared by analysis of variance. Safety and tolerability were also evaluated. RESULTS: A total of 30 healthy adults (mean age, 43.1 years) were randomized. The majority of the subjects were white men. The geometric mean ratios for natural log transformed Cmax, AUC0-t, and AUC0-∞ of olopatadine in GSP301 and OLO-sponsor were 86.63, 86.92, and 92.83, respectively. For GSP301 and OLO, geometric mean ratios for Cmax, AUC0-t, and AUC0-∞ were 84.68, 87.87, and 93.80, respectively. The percentage of subjects who reported treatment-emergent adverse events (AE) for GSP301, OLO-sponsor, and OLO were 13.8, 10.3, and 10.0%, respectively, with mild AEs reported. One subject withdrew from the study due to an AE (minor oropharyngeal pain) during OLO treatment, before receiving GSP301. CONCLUSION: Olopatadine bioavailability with GSP301 was comparable with OLO-sponsor and OLO. The presence of mometasone in GSP301 did not considerably affect the PK of olopatadine. GSP301 was well tolerated, with only mild AEs reported.

Efficacy and safety of beclomethasone dipropionate nasal aerosol in children with perennial allergic rhinitis.

BACKGROUND: Beclomethasone dipropionate (BDP) nasal aerosol (non-aqueous) is approved for management of seasonal and perennial allergic rhinitis (PAR) in adolescents and adults. OBJECTIVE: To evaluate the efficacy and safety of BDP nasal aerosol at 80 µg/day in children with PAR. METHODS: This 12-week, phase 3, double-blinded, placebo-controlled, parallel-group study randomized 547 children (4-11 years old) with PAR to once-daily BDP nasal aerosol at 80 µg/day or placebo. The primary end point was change from baseline in average morning and evening reflective total nasal symptom score (rTNSS) during the first 6 weeks of treatment in patients 6 to 11 years old. Changes from baseline in average morning and evening instantaneous TNSS (iTNSS) in children 6 to 11 years old and average rTNSS and iTNSS in children 4 to 11 years old were assessed during the first 6 weeks of treatment. RESULTS: Improvements were significantly greater with BDP nasal aerosol than with placebo during the first 6 weeks of treatment in children 6 to 11 years old in average morning and evening rTNSS and iTNSS (mean treatment difference -0.66 [P = .002] and -0.58 [P = .004], respectively). Improvements in average morning and evening rTNSS and iTNSS also were significantly greater in patients 4 to 11 years receiving BDP nasal aerosol than with placebo during the first 6 weeks of treatment (P = .002 and P = .004, respectively). Similar improvements were seen during 12 weeks of treatment. The safety profile of BDP nasal aerosol was comparable to that of placebo. CONCLUSION: The BDP nasal aerosol at 80 µg/day in children 4 to 11 years old was well tolerated and effective in controlling nasal symptoms of PAR. TRIAL REGISTRATION: www.clinicaltrials.gov, identifier NCT01783548.

No hypothalamic-pituitary-adrenal function effect with beclomethasone dipropionate nasal aerosol, based on 24-hour serum cortisol in pediatric allergic rhinitis.

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.

Long-term efficacy and safety of once-daily treatment with beclomethasone dipropionate nasal aerosol.

Beclomethasone dipropionate (BDP) nasal aerosol has an established efficacy and safety profile for short-term allergic rhinitis (AR) treatment. However, managing perennial AR (PAR) symptoms often requires long-term treatment. This study evaluates efficacy and safety of long-term treatment with BDP nasal aerosol in PAR patients. In this double-blind, placebo-controlled study, patients (≥12 years [n = 529]) were randomized 4:1 to once-daily treatment with BDP nasal aerosol at 320 µg or placebo. The primary efficacy end point was change from baseline in weekly averages of patient-reported 24-hour reflective total nasal symptom score (rTNSS) over 30 weeks. Safety and tolerability of BDP nasal aerosol were also assessed. Ocular safety, including changes in intraocular pressure and severity of lens opacities (nuclear opalescence, nuclear color, cortical lens opacity, and posterior subcapsular lens opacity), was measured for patients who completed 52 weeks of treatment (n = 245). Across 30 and 52 weeks, BDP nasal aerosol significantly improved rTNSS and instantaneous TNSS (iTNSS) versus placebo (least-squares mean treatment difference, rTNSS, -0.97 for 30 weeks and -1.09 for 52 weeks, p < 0.001 for both; iTNSS, -0.96 for 30 weeks and -1.10 for 52 weeks], p < 0.001 for both). BDP nasal aerosol was well tolerated. Incidence of most adverse events with BDP nasal aerosol was similar to that with placebo, except for epistaxis, which occurred more frequently with active treatment. Severity of changes from baseline in ocular lens opacities was comparable between treatments. BDP nasal aerosol at 320 µg once daily was safe and effective for long-term PAR treatment, with no evidence of clinically adverse systemic safety events. This study was a part of the clinical trial NCT00988247 registered at www.ClinicalTrials.gov.

Efficacy and safety of beclomethasone dipropionate nasal aerosol in pediatric patients with seasonal allergic rhinitis.

BACKGROUND: Aerosolized intranasal corticosteroid formulations are desirable for many patients with allergic rhinitis (AR), especially children, who wish to avoid the "wet feeling" and "drip down the throat" associated with aqueous formulations. Beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol has been shown to be safe and effective in adolescents and adults with AR. OBJECTIVE: To evaluate the efficacy and safety of BDP nasal aerosol in pediatric patients with moderate to severe seasonal AR. METHODS: In this double-blinded, placebo-controlled study, children (6-11 years of age) with seasonal AR were randomized to once-daily treatment with BDP nasal aerosol 80 µg (n = 239) or 160 µg (n = 242) or placebo (n = 234). The primary end point was change from baseline in average morning and evening reflective total nasal symptom score over the 2-week treatment period. RESULTS: Treatment with BDP nasal aerosol showed significantly greater improvements in average morning and evening reflective total nasal symptom score vs placebo (80 µg, -0.71; 160 µg, -0.76; P < .001 for the 2 comparisons). Similarly, significantly greater improvements in average morning and evening instantaneous total nasal symptom score were seen with BDP nasal aerosol vs placebo (80 µg, -0.63; 160 µg, -0.73; P < .001 for the 2 comparisons). The incidence of adverse events from BDP nasal aerosol was comparable to that from placebo. CONCLUSION: BDP nasal aerosol (80 or 160 µg/d) provided significant and clinically meaningful nasal symptom relief and an established overall safety profile similar to that of placebo, suggesting that it is an effective and well-tolerated treatment option for pediatric patients with moderate to severe seasonal AR. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT012073190.

Patient satisfaction with beclomethasone dipropionate nasal aerosol device with integrated dose counter during daily use.

Some patients with allergic rhinitis (AR) may prefer a "dry" intranasal corticosteroid aerosol to avoid certain sensory perceptions such as the "wet feeling in the nose" and the "dripping down the throat" associated with aqueous nasal sprays. A nonaqueous hydrofluoroalkane-propelled beclomethasone dipropionate (BDP) nasal aerosol with an established efficacy and safety profile was approved to treat the nasal symptoms associated with AR in adult and adolescent patients. This study was designed to evaluate ease of use and patient satisfaction with the BDP nasal aerosol device in patients with perennial AR (PAR). In this phase 3, randomized, double-blind, parallel-group, placebo-controlled study, eligible patients (≥12 years of age) with PAR were randomly assigned to receive BDP nasal aerosol at 320 micrograms/day or placebo for 6 weeks. At the end of the treatment period, patients assessed device ease of use and satisfaction with the device using a questionnaire with a 5-point representative scale (not at all, not very, neither nor, somewhat, very [certain/easy/satisfactory]). Nearly all patients (89.7%) reported that the BDP nasal aerosol device with integrated dose counter was "very easy" or "somewhat easy" to use. The majority of patients (87.5%) also indicated that it was "very easy" or "somewhat easy" to tell when the device was empty, compared with only 42.3% who were "very certain" or "somewhat certain" of being able to tell when previously used aqueous nasal spray devices were empty. Overall, patient satisfaction with the BDP nasal aerosol device was high: 65.7% responded that they were "very satisfied" or "somewhat satisfied" and only 3.6% were "not satisfied at all" or "not very satisfied." These results indicate that the majority of patients considered the BDP nasal aerosol device easy to use and reported a high degree of satisfaction with the device compared with other nasal sprays they had used in the past.

Beclomethasone dipropionate nasal aerosol with an integrated dose counter: functionality and performance.

Consistent medication delivery is critical for disease control including symptom management of allergic rhinitis (AR). Available aqueous intranasal corticosteroid devices lack an accurate dose (actuation) counter, which may lead patients to prematurely discard a unit or use a unit beyond its labeled number of actuations, therefore impacting patient adherence. Beclomethasone dipropionate (BDP) nasal aerosol, a nonaqueous hydrofluoroalkane formulation in a device with a novel integrated dose counter and an established efficacy/safety profile, was approved to treat AR-associated nasal symptoms in adolescent and adult patients. This study was designed to evaluate performance of the BDP nasal aerosol device with an integrated dose counter in perennial AR (PAR) patients. In a 6-week, double-blind, placebo-controlled study in PAR patients (≥12 years), patients were randomized to receive once-daily BDP nasal aerosol at 320 micrograms or placebo. In addition to assessing the primary efficacy end point, patients evaluated the performance of the device and reliability, accuracy, and functionality of the dose counter. Concordance between daily patient-reported actuations and dose counter readings was assessed by classifying discrepancies into four categories: "fire not count," "count not fire," "count unknown fire," and "count up unknown fire." Analysis was performed for the total device completer population (n = 374), which included all randomized patients completing ≥80% of actuations during the last 4 weeks of treatment. Low discrepancy rates were shown for all discrepancy categories. Of 41,891 patient-reported actuations, only 159 discrepancies (diary versus counter) were noted, resulting in an overall discrepancy rate of 0.38 per 100 actuations. The medically important discrepancy rate of "fire not count" was low (0.09 per 100 actuations). Overall, 79.1% of patients reported zero discrepancies, 9.4% reported one discrepancy, and 6.4% reported two discrepancies. These results showed the functionality and reliability of the BDP nasal aerosol device with an integrated dose counter in a clinical setting. (ClinicalTrials.gov identifier: NCT01134705.).

Once-daily treatment with beclomethasone dipropionate nasal aerosol does not affect hypothalamic-pituitary-adrenal axis function.

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.

Safety and efficacy of once-daily treatment with beclomethasone dipropionate nasal aerosol in subjects with perennial allergic rhinitis.

Intranasal corticosteroids are recommended as first-line therapy for the treatment of the symptoms of persistent allergic rhinitis (AR). Since the phase-out of chlorofluorocarbon nasal aerosols, intranasal corticosteroids have been available only as aqueous nasal sprays. This study was designed to assess the efficacy, safety, and quality-of-life benefits of beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol in subjects with perennial AR (PAR). After a 7- to 21-day placebo run-in period, eligible subjects aged ≥12 years with PAR were randomized to 6 weeks of once-daily treatment with BDP nasal aerosol at 320 µg or placebo. Reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS, respectively), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, and physician-assessed total nasal symptom score were evaluated. The primary end point was change from baseline in average morning (A.M.) and evening (P.M.) subject-reported rTNSS over the 6-week treatment period. Safety and tolerability were also assessed. Treatment with BDP nasal aerosol showed significantly greater improvement in average A.M. and P.M. rTNSS compared with placebo (mean treatment difference, -0.84; 95% confidence interval, -1.2, -0.5; p < 0.001). Greater improvements in rTNSS were reported as early as day 1 and were maintained throughout the 6-week treatment period with the exception of day 2. Greater improvements were seen for all four individual nasal symptoms (nasal congestion, nasal itching, rhinorrhea, and sneezing) with BDP nasal aerosol compared with placebo. Similarly, significant improvements were seen in average A.M. and P.M. iTNSS (p < 0.001) and RQLQ score (p = 0.001) with BDP nasal aerosol compared with placebo. In addition, BDP nasal aerosol treatment was well tolerated, and its safety profile was comparable to that of placebo. This clinical study indicated that treatment with BDP nasal aerosol provides statistically significant and clinically meaningful nasal symptom relief accompanied by improved quality of life in subjects with PAR. Additionally, treatment with BDP nasal aerosol was well tolerated with a safety profile comparable to that of placebo. This study was part of the clinical trial NCT01134705 registered in www.ClinicalTrials.gov.

Efficacy and safety of once-daily treatment with beclomethasone dipropionate nasal aerosol in subjects with seasonal allergic rhinitis.

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.

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.

Pharmacokinetic profile of beclomethasone dipropionate hydrofluoroalkane after intranasal administration versus oral inhalation in healthy subjects: results of a single-dose, randomized, open-label, 3-period crossover study.

BACKGROUND: Beclomethasone dipropionate (BDP) is an anti-inflammatory corticosteroid that is rapidly metabolized to the pharmacologically active monoester, beclomethasone-17-monopropionate (17-BMP). Recently, a hydrofluoroalkane (HFA)-propelled nasal aerosol formulation of BDP was developed to treat allergic rhinitis. However, the pharmacokinetic profile of BDP HFA nasal aerosol has not been previously investigated. OBJECTIVE: This study evaluated and compared the systemic levels of 17-BMP and BDP after a single dose of intranasally administered or orally inhaled BDP HFA in healthy subjects. METHODS: In this single-center, randomized, open-label, 3-period crossover study, healthy subjects received single doses of intranasal BDP HFA (80 and 320 µg) and orally inhaled BDP HFA (320 µg). The primary pharmacokinetic parameters assessed were area under the concentration-time curve until the last measurable value (AUC(last)) and C(max) for 17-BMP. For AUC(last) and C(max), point estimates for treatment differences and CIs were calculated on the log scale and then exponentiated to provide estimates of the geometric mean ratios (GMRs) and associated CIs. RESULTS: Thirty subjects were randomized to receive study medication (aged 18-45 years, 66.7% male). Mean plasma concentrations of 17-BMP after intranasal administration of BDP HFA (for both 80- and 320-µg doses) were substantially lower than that of orally inhaled BDP HFA (320 µg) across all time points. Mean AUC(last) values of 17-BMP for intranasal 80 µg, intranasal 320 µg, and orally inhaled 320 µg were 295.8, 1139.7, and 4140.3 pg·hr/mL, respectively. Mean C(max) values were 92.1, 262.7, and 1343.7 pg/mL, respectively. The GMR of AUC(last) for 17-BMP with intranasal BDP HFA 320 µg versus orally inhaled BDP HFA 320 µg was 0.275, indicating substantially lower systemic bioavailability with intranasal administration than with oral inhalation. Similarly, the GMR of AUC(last) for 17-BMP with intranasal BDP HFA 80 µg versus 320 µg was 0.260, suggesting approximate dose proportionality (4-fold difference). Pharmacokinetic results for BDP were similar to those seen for 17-BMP. All doses of intranasal and orally inhaled BDP HFA were well tolerated, and no treatment-related adverse events were reported. CONCLUSIONS: The results of this study suggest that 80 and 320 µg BDP HFA nasal aerosols have substantially lower systemic bioavailability than 320 µg orally inhaled BDP HFA in healthy subjects. All treatments were well tolerated. ClinicalTrials.gov identifier: NCT01537692.