Calvin J. Small

Efficacy and safety of beclomethasone dipropionate breath-actuated or metered-dose inhaler in pediatric patients with asthma

BACKGROUND Breath-actuated inhalers (BAI) eliminate the need for hand-breath coordination and, therefore, simplify the delivery of inhaled medication. OBJECTIVE To evaluate the efficacy and safety of beclomethasone dipropionate BAI and metered-dose inhaler (MDI) versus placebo in pediatric patients ages 4-11 years with persistent asthma. METHODS In this double-blind, double-dummy, phase III study, 628 children with persistent asthma were randomly assigned (1:1:1:1:1) to twice-daily beclomethasone dipropionate (BAI 80 μg/day, BAI 160 μg/day, MDI 80 μg/day, or MDI 160 μg/day) or to placebo. Efficacy over 12 weeks was assessed by spirometry, peak expiratory flow (PEF) measurements and other clinical end points. The primary efficacy end point was the baseline-adjusted trough morning percent predicted forced expiratory volume in 1 second (PPFEV1) area under the effect curve from 0 to 12 weeks (AUEC[0-12 weeks]). RESULTS PPFEV1 AUEC(0-12 weeks) showed numerical improvements from baseline in the BAI 80 μg/day and BAI 160 μg/day groups and MDI 80 μg/day and MDI 160 μg/day groups; however, these improvements were not significant versus placebo for any group after hierarchical testing was applied. Consistent improvements were noted in the active treatment groups versus placebo for the weekly average trough morning and evening PEFs, and with BAI 80 μg/day versus placebo for rescue albuterol/salbutamol use and the total daily asthma symptom score. Most patients indicated that the BAI device was easy or very easy to use. Adverse events were comparable across the groups; the incidence of oral candidiasis ranged from 0.8 to 3.2%. CONCLUSIONS Although the primary efficacy end point was not demonstrated, consistent improvements in PEF and other clinical end points were observed with beclomethasone dipropionate BAI, particularly at the 80 μg/day dose. These clinical benefits, combined with the need for better symptom control in children with asthma, supported the development of beclomethasone dipropionate BAI.

Randomized trial to assess the efficacy and safety of beclomethasone dipropionate breath-actuated inhaler in patients with asthma

BACKGROUND Breath-actuated inhalers (BAI) eliminate the need for the hand-breath coordination required with standard metered-dose inhalers (MDI). OBJECTIVE To evaluate the efficacy and safety of beclomethasone dipropionate (BDP) administered via BAI. METHODS This 6-week, phase III, double-blind study included patients aged ≥12 years with persistent asthma. During the single-blind run-in, patients discontinued asthma medications and received twice-daily placebo BAI or MDI. At randomization, BAI patients received BDP BAI 320 μg/day, BDP BAI 640 μg/day, or placebo BAI, and MDI patients received BDP MDI 320 μg/day or placebo MDI. Assessments included standardized baseline-adjusted trough morning forced expiratory volume in 1 second (FEV1) area under the effect curve from 0 to 6 weeks (AUEC[0-6 wk]) (obtained by clinic-based spirometry; the primary end point), morning peak expiratory flow (PEF), trough daily morning FEV1 (obtained by handheld spirometry), withdrawals, and tolerability. RESULTS Of 425 patients randomized, most were white (81%) and female (61%). BDP BAI 320 and 640 μg/day significantly improved FEV1 AUEC(0-6 wk) versus placebo (p < 0.001). The BDP BAI treatment groups exhibited significantly improved morning PEF and daily morning FEV1 versus placebo (p < 0.001). Similar treatment effects were demonstrated for BDP MDI (p < 0.001). Fewer patients withdrew due to worsening asthma while taking BDP BAI 320 μg/day (n = 1), BDP BAI 640 μg/day (n = 0), and BDP MDI 320 μg/day (n = 1) versus placebo (n = 10). BDP BAI was well tolerated. CONCLUSION BDP BAI demonstrated significant improvements in pulmonary function versus placebo, with results similar to BDP MDI. The safety profile of BDP BAI was comparable to BDP MDI, with no new safety signals.The study was registered on ClinicalTrials.gov (NCT02513160), www.clinicaltrials.gov.

The Efficacy and Safety of Beclomethasone Dipropionate Delivered via a Breath-Actuated Inhaler in Adult and Adolescent Patients With Persistent Asthma

Background: To evaluate the efficacy and safety of beclomethasone dipropionate (BDP) delivered via a breath-actuated inhaler (BAI) versus placebo in asthmatic patients. Methods: This phase 3, 6-week, double-blind study (NCT02513160) included patients with persistent asthma (aged ≥12 years). During a 14-to 30-day single-blind run-in, patients discontinued asthma medications and received albuterol metered-dose inhaler (MDI) for rescue and twicedaily placebo BAI or MDI for training. At randomization, BAI patients received BDP BAI 320 mcg/day, BDP BAI 640 mcg/day, or placebo BAI. MDI patients were randomized to receive BDP MDI 320 mcg/day or placebo MDI. Standardized baseline-adjusted trough morning forced expiratory volume in 1 second area under the effect curve from 0 to 6 weeks (FEV1AUEC0–6wk; primary), morning peak expiratory flow (PEF), rescue medication use, asthma symptoms, withdrawals, and tolerability were assessed. Results: The modified intent-to-treat and safety populations each included 425 patients. BDP BAI 320 and 640 mcg/day significantly improved FEV1AUEC0–6wk versus placebo (P<0.0001). Active BAI treatment groups exhibited significantly improved morning PEF, rescue medication use, and asthma symptoms versus placebo (P≤0.0003). Similar treatment effects were demonstrated for BDP MDI (P≤0.0006). Fewer patients withdrew due to worsening asthma while taking BDP BAI 320 mcg/day (n=1), BDP BAI 640 mcg/day (n=0), and BDP MDI 320 mcg/day (n=1) versus placebo (n=10). BDP BAI was safe and well tolerated. Conclusions: BDP BAI demonstrated significant improvements in lung function and symptom control versus placebo with similar results for BDP MDI. BDP BAI’s safety profile was comparable to BDP MDI, with no new safety signals.

Evaluation of beclomethasone dipropionate (80 and 160 micrograms/day) delivered via a breath-actuated inhaler for persistent asthma

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.

Safety and efficacy of beclomethasone dipropionate delivered by breath-actuated or metered-dose inhaler for persistent asthma.

BACKGROUND Breath-actuated inhalers (BAI) have been developed to simplify the delivery of inhaled medication. OBJECTIVE To evaluate the safety and efficacy of beclomethasone dipropionate hydrofluoroalkane BAI and metered-dose inhaler (MDI) versus placebo in patients who previously used a mid- to high-dose inhaled corticosteroid or inhaled corticosteroid/long-acting beta agonist for persistent asthma. METHODS This phase III study included five treatment groups: placebo, and four beclomethasone dipropionate groups (BAI 320 μg/day, BAI 640 μg/day, MDI 320 μg/day, and MDI 640 μg/day). Efficacy over 12 weeks was assessed by spirometry, peak flow measurements, and other clinical end points. Safety was assessed by adverse events. RESULTS Baseline-adjusted trough morning forced expiratory volume in 1 second area under the effect curve from time 0 to 12 weeks (primary end point) was increased in the BAI 320 and BAI 640 μg/day groups and the MDI 640 μg/day group versus placebo (not significant). Clinically important improvements were noted in morning and evening peak expiratory flow and decreased rescue medications. More patients who received placebo than patients in active treatment groups withdrew due to meeting the stopping criteria for worsening asthma. Patients in the active treatment groups experienced a greater decrease in asthma symptoms than patients in the placebo group. Quality of life and Asthma Control Test scores improved in the active treatment groups compared with the placebo group (p ≤ 0.0074). The most common adverse events (>5% in any group) were oral candidiasis and upper respiratory tract infection. CONCLUSION Clinical benefits for patients who used BAI 320 and 640 μg/day and MDI 640 μg/day were demonstrated. The safety profiles of BAI 320 and 640 μg/day were comparable with that of the MDI. These benefits and the continued need for better symptom control among patients with asthma support the continued development of this controller medication. ClinicalTrials.gov identifier NCT02031640.

Once-Daily Treatment with Beclomethasone Dipropionate (BDP) Nasal Aerosol Is Effective in Improving Total Nasal Symptom Scores (TNSS) in Children with Seasonal Allergic Rhinitis (SAR) Regardless of Baseline Symptom Severity

Rationale: Beclomethasone dipropionate (BDP) nasal aerosol (a nonaqueous formulation) is approved for management of seasonal and perennial allergic rhinitis (PAR) in adolescents and adults. This post hoc analysis evaluated the effectiveness of BDP nasal aerosol based on baseline symptom severity in children with PAR. Methods: This 12-week, double-blind, placebo-controlled study evaluated children aged 4–11 years with PAR randomized to BDP nasal aerosol 80 mcg/day; n=362) or placebo (n=185). Efficacy assessments included change from baseline in patientreported average AM and PM reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS) over 6 weeks for children aged 6–11 years (primary variable) evaluated by baseline symptom severity: less severe (baseline rTNSS or iTNSS < baseline median) and more severe (baseline rTNSS or iTNSS ≥ baseline median). Results: Treatment with BDP nasal aerosol improved average AM and PM rTNSS versus placebo in children with more severe baseline symptoms (least squares mean [95% confidence interval] difference: −0.70 [−1.31, −0.08]; P=0.027) and less severe baseline symptoms (−0.64 [−1.20, −0.08]; P=0.026) over the 6 weeks. Treatment with BDP nasal aerosol improved average AM/PM iTNSS versus placebo in children with more severe baseline symptoms (−0.72 [−1.32, −0.12]; P=0.019); however, in children with less severe baseline symptoms, the improvement did not reach statistical significance (80 mcg −0.43 [−0.92, 0.07]; P=0.094). Conclusions: In this post hoc analysis, BDP nasal aerosol treatment in children with PAR resulted in significant improvements versus placebo in rTNSS regardless of baseline symptom severity and in iTNSS in the group with more severe symptoms at baseline.