Trial Outcomes & Findings for Study to Assess the Efficacy and Safety of Beclomethasone Dipropionate in Adolescent and Adult Patients 12 Years of Age and Older With Persistent Asthma (NCT NCT02513160)

Last Updated: 2021-11-09

Results Overview

The primary efficacy variable was the standardized baseline-adjusted trough morning (pre-dose and pre-rescue bronchodilator) FEV1 AUEC(0-6wk). Pulmonary function measurements such as FEV1 were obtained electronically by spirometry at the randomization visit, each treatment visit (Weeks 2, 4 and 6) and any unscheduled visit (such as the early termination visit). The highest FEV1 value from 3 acceptable and 2 repeatable maneuvers (maximum of 8 attempts) was used. The least-square (LS) means, difference of LS means and its 95% confidence interval (CI), and p-value represent the results obtained from the analysis of covariance with covariate adjustment for baseline, sex, age, current asthma therapy, and treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

713 participants

Primary outcome timeframe

Baseline (Day 0 of Treatment Period), weeks 2, 4, 6

Results posted on

2021-11-09

Participant Flow

A total of 1089 patients with asthma were screened for enrollment into this study at 67 study centers in the US.

Of the screened patients, 376 patients were not enrolled; 312 were excluded on the basis of inclusion/exclusion criteria, 19 patients withdrew consent, 10 patients were lost to follow-up before the baseline visit, 1 patient reported an adverse event before entering run-in and the reason for screen failure was "Other" for 34 patients.

Participant milestones

Participant milestones
Measure	Placebo Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 320 mcg/Day Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 640 mcg/Day Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (80 mcg/inhalation), twice daily for a total daily dose of 640 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	MDI 320 mcg/Day Beclomethasone dipropionate metered-dose inhaler (MDI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
Run-In Period (Days -14 to Day -1) STARTED	713	0	0	0
Run-In Period (Days -14 to Day -1) COMPLETED	425	0	0	0
Run-In Period (Days -14 to Day -1) NOT COMPLETED	288	0	0	0
Treatment Period (Day 0 to Week 6) STARTED	107	108	105	105
Treatment Period (Day 0 to Week 6) COMPLETED	101	104	104	103
Treatment Period (Day 0 to Week 6) NOT COMPLETED	6	4	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 320 mcg/Day Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 640 mcg/Day Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (80 mcg/inhalation), twice daily for a total daily dose of 640 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	MDI 320 mcg/Day Beclomethasone dipropionate metered-dose inhaler (MDI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
Run-In Period (Days -14 to Day -1) Inclusion criteria not met	33	0	0	0
Run-In Period (Days -14 to Day -1) Failure to meet randomization criteria	214	0	0	0
Run-In Period (Days -14 to Day -1) Exclusion criteria met	6	0	0	0
Run-In Period (Days -14 to Day -1) Adverse Event	4	0	0	0
Run-In Period (Days -14 to Day -1) Withdrawal by Subject	20	0	0	0
Run-In Period (Days -14 to Day -1) Site reached randomization limit	1	0	0	0
Run-In Period (Days -14 to Day -1) Lost to Follow-up	10	0	0	0
Treatment Period (Day 0 to Week 6) Withdrawal by Subject	2	2	0	1
Treatment Period (Day 0 to Week 6) Noncompliance	1	0	0	0
Treatment Period (Day 0 to Week 6) Lost to Follow-up	2	1	1	1
Treatment Period (Day 0 to Week 6) Lack of Efficacy	1	0	0	0
Treatment Period (Day 0 to Week 6) Did not meet exclusion criteria	0	1	0	0

Baseline Characteristics

Study to Assess the Efficacy and Safety of Beclomethasone Dipropionate in Adolescent and Adult Patients 12 Years of Age and Older With Persistent Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=107 Participants Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 320 mcg/Day n=108 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 640 mcg/Day n=105 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (80 mcg/inhalation), twice daily for a total daily dose of 640 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	MDI 320 mcg/Day n=105 Participants Beclomethasone dipropionate metered-dose inhaler (MDI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	Total n=425 Participants Total of all reporting groups
Age, Continuous	39.2 years STANDARD_DEVIATION 13.33 • n=5 Participants	41.8 years STANDARD_DEVIATION 14.29 • n=7 Participants	42.6 years STANDARD_DEVIATION 14.19 • n=5 Participants	43.1 years STANDARD_DEVIATION 16.04 • n=4 Participants	41.7 years STANDARD_DEVIATION 14.52 • n=21 Participants
Age, Customized 12-17 years	8 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants	21 Participants n=21 Participants
Age, Customized 18-64 years	98 Participants n=5 Participants	101 Participants n=7 Participants	94 Participants n=5 Participants	85 Participants n=4 Participants	378 Participants n=21 Participants
Age, Customized >=65 years	1 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	13 Participants n=4 Participants	26 Participants n=21 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	68 Participants n=7 Participants	67 Participants n=5 Participants	59 Participants n=4 Participants	260 Participants n=21 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	40 Participants n=7 Participants	38 Participants n=5 Participants	46 Participants n=4 Participants	165 Participants n=21 Participants
Race/Ethnicity, Customized White	87 Participants n=5 Participants	92 Participants n=7 Participants	83 Participants n=5 Participants	84 Participants n=4 Participants	346 Participants n=21 Participants
Race/Ethnicity, Customized Black	15 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants	17 Participants n=4 Participants	63 Participants n=21 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	10 Participants n=21 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	89 Participants n=5 Participants	90 Participants n=7 Participants	93 Participants n=5 Participants	88 Participants n=4 Participants	360 Participants n=21 Participants
Race/Ethnicity, Customized Hispanic or Latino	18 Participants n=5 Participants	18 Participants n=7 Participants	12 Participants n=5 Participants	17 Participants n=4 Participants	65 Participants n=21 Participants
Weight	84.06 kg STANDARD_DEVIATION 25.337 • n=5 Participants	89.93 kg STANDARD_DEVIATION 24.719 • n=7 Participants	85.71 kg STANDARD_DEVIATION 25.590 • n=5 Participants	88.56 kg STANDARD_DEVIATION 23.820 • n=4 Participants	87.07 kg STANDARD_DEVIATION 24.987 • n=21 Participants
Height	167.34 cm STANDARD_DEVIATION 10.138 • n=5 Participants	169.30 cm STANDARD_DEVIATION 9.457 • n=7 Participants	167.82 cm STANDARD_DEVIATION 8.753 • n=5 Participants	169.14 cm STANDARD_DEVIATION 8.770 • n=4 Participants	168.40 cm STANDARD_DEVIATION 9.308 • n=21 Participants
Body Mass Index	29.909 kg/m^2 STANDARD_DEVIATION 8.4253 • n=5 Participants	31.315 kg/m^2 STANDARD_DEVIATION 8.1551 • n=7 Participants	30.327 kg/m^2 STANDARD_DEVIATION 8.3470 • n=5 Participants	30.944 kg/m^2 STANDARD_DEVIATION 8.1645 • n=4 Participants	30.625 kg/m^2 STANDARD_DEVIATION 8.2624 • n=21 Participants
Duration of Asthma <3 months	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Duration of Asthma 3 months to <6 months	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Duration of Asthma 6 months to <1 year	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Duration of Asthma 1 year to <5 years	5 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	24 Participants n=21 Participants
Duration of Asthma 5 years to <10 years	6 Participants n=5 Participants	11 Participants n=7 Participants	7 Participants n=5 Participants	8 Participants n=4 Participants	32 Participants n=21 Participants
Duration of Asthma 10 years to <15 years	12 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	12 Participants n=4 Participants	39 Participants n=21 Participants
Duration of Asthma >=15 years	84 Participants n=5 Participants	81 Participants n=7 Participants	84 Participants n=5 Participants	80 Participants n=4 Participants	329 Participants n=21 Participants
Current Asthma Therapy Inhaled corticosteroid	66 Participants n=5 Participants	66 Participants n=7 Participants	65 Participants n=5 Participants	65 Participants n=4 Participants	262 Participants n=21 Participants
Current Asthma Therapy Non-corticosteroid	41 Participants n=5 Participants	42 Participants n=7 Participants	40 Participants n=5 Participants	40 Participants n=4 Participants	163 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0 of Treatment Period), weeks 2, 4, 6

Population: The modified intent-to-treat (mITT) analysis set included all patients in the ITT analysis set and included the available data for those patients until they discontinued study drug treatment at treatment visit week 6 or last available study visit.

Outcome measures

Outcome measures
Measure	Placebo n=105 Participants Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 320 mcg/Day n=105 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 640 mcg/Day n=104 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (80 mcg/inhalation), twice daily for a total daily dose of 640 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	MDI 320 mcg/Day n=103 Participants Beclomethasone dipropionate metered-dose inhaler (MDI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
Standardized Baseline-Adjusted Trough Morning Forced Expiratory Volume in One Minute (FEV1) Area Under the Effect Curve From Time Zero to 6 Weeks (AUEC(0-6wk))	62 milliliters Standard Error 23.0	205 milliliters Standard Error 23.2	212 milliliters Standard Error 23.3	210 milliliters Standard Error 23.0

SECONDARY outcome

Timeframe: Timeframes: Baseline (Day -7 to Day 0 which is part of the Run-in Period); Treatment Period from Day 0 up to 6 weeks

Change from baseline in the weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF by handheld spirometer over the 6-week treatment period. PEF were determined twice daily, in the morning and in the evening, before administration of study drug or rescue medications. A handheld spirometer was provided to patients and used to determine the morning and evening PEF throughout the study. The spirometer was programmed to record the highest PEF obtained from 3 valid attempts. Baseline was defined as the average of recorded trough morning PEF assessments over the 7 days prior to the first dose of double-blind study treatment, including the morning assessment at the randomization visit. The LS means, difference of LS means and its 95% confidence interval, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week, and treatment by week interaction.

Outcome measures

Outcome measures
Measure	Placebo n=106 Participants Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 320 mcg/Day n=108 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 640 mcg/Day n=105 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (80 mcg/inhalation), twice daily for a total daily dose of 640 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	MDI 320 mcg/Day n=104 Participants Beclomethasone dipropionate metered-dose inhaler (MDI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Rate Over the 6-Week Treatment Period	-10.0 liters/minute Standard Error 4.31	20.1 liters/minute Standard Error 4.30	11.9 liters/minute Standard Error 4.28	10.9 liters/minute Standard Error 4.28

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day 0 which is part of the Run-in Period); Treatment Period from Day 0 up to 6 weeks

Change from baseline in the weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) FEV1 by handheld spirometer over the 6-week treatment period. FEV1 were determined twice daily, in the morning and in the evening, before administration of study drug or rescue medications. A handheld spirometer was provided to patients and used to determine the morning and evening FEV1 throughout the study. The spirometer was programmed to record the highest FEV1 obtained from 3 valid attempts. Baseline was defined as the average of recorded trough morning FEV1 assessments over the 7 days prior to the first dose of double-blind study treatment, including the morning assessment at the randomization visit. The LS means, difference of LS means and its 95% confidence interval, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week, and treatment by week interaction.

Outcome measures

Outcome measures
Measure	Placebo n=106 Participants Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 320 mcg/Day n=108 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 640 mcg/Day n=105 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (80 mcg/inhalation), twice daily for a total daily dose of 640 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	MDI 320 mcg/Day n=104 Participants Beclomethasone dipropionate metered-dose inhaler (MDI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
Change From Baseline in Weekly Average of Daily Trough Morning Forced Expiratory Volume in One Minute (FEV1) Rate Over the 6-Week Treatment Period	-8 milliliters Standard Error 26.0	162 milliliters Standard Error 25.8	135 milliliters Standard Error 25.9	125 milliliters Standard Error 25.8

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day 0 which is part of the Run-in Period); Treatment Period from Day 0 up to 6 weeks

Change from baseline in the weekly average of total daily (24-hour) use of albuterol/salbutamol inhalation aerosol over weeks 1 through 6. Patients recorded the number of inhalations (puffs used) of rescue medication (albuterol/salbutamol HFA MDI \[90 mcg ex-actuator\] or equivalent) each morning and evening in the diary. The average number of daily inhalations over the 7 days before the randomization visit was the baseline value and was compared with the rescue medication use during the 6-week treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=106 Participants Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 320 mcg/Day n=108 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 640 mcg/Day n=105 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (80 mcg/inhalation), twice daily for a total daily dose of 640 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	MDI 320 mcg/Day n=104 Participants Beclomethasone dipropionate metered-dose inhaler (MDI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
Change From Baseline in Weekly Average of Total Daily (24-Hour) Rescue Medication Use Over the 6-Week Treatment Period	0.37 number of inhalations Standard Error 0.140	-0.73 number of inhalations Standard Error 0.139	-0.66 number of inhalations Standard Error 0.140	-0.66 number of inhalations Standard Error 0.139

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day 0 which is part of the Run-in Period); Treatment Period from Day 0 up to 6 weeks

Asthma symptom scores were recorded in the patient's diary each morning and evening before determining FEV1 and PEF and before administration of study or rescue medications. The Daytime Symptom Score was recorded in the evening on a scale of 0 (No symptoms during the day) to 5 (Symptoms so severe that I could not go to work or perform normal daily activities) plus the Nighttime Symptom Score in the morning on a scale of 0 (No symptoms during the night) to 4 (Symptoms so severe that I did not sleep at all) for a total score range of 0-9. Baseline was defined as the average of recorded daily asthma symptom scores (average of daytime and nighttime score) over the 7 days prior to the first dose of double-blind study treatment, including the morning assessment at the randomization visit. The LS means, difference of LS means and its 95% CI, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asth

Outcome measures

Outcome measures
Measure	Placebo n=106 Participants Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 320 mcg/Day n=107 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 640 mcg/Day n=105 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (80 mcg/inhalation), twice daily for a total daily dose of 640 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	MDI 320 mcg/Day n=104 Participants Beclomethasone dipropionate metered-dose inhaler (MDI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
Change From Baseline in Weekly Average of Total Daily Asthma Symptom Score Over the 6-Week Treatment Period	0.06 units on a scale Standard Error 0.043	-0.18 units on a scale Standard Error 0.043	-0.26 units on a scale Standard Error 0.043	-0.24 units on a scale Standard Error 0.043

SECONDARY outcome

Timeframe: Day 0 to Week 6

Number of participants who were withdrawn from study drug due to worsening asthma. Alert criteria for individual patients with worsening asthma were designed to ensure patient safety. The investigator determined whether the patient's overall clinical picture was consistent with worsening asthma and if the patient should be withdrawn from study drug treatment (but not the study) and be placed on appropriate asthma therapy in the interest of patient safety. An example of an alert criteria is: * Morning FEV1 by handheld spirometer as measured at home falls below the FEV1 stability limit (FEV1 \<80%) as calculated at the screening visit for the Run-in Period and at the randomization visit (Day 0) for the Treatment Period on 4 or more days out of any 7-day period.

Outcome measures

Outcome measures
Measure	Placebo n=107 Participants Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 320 mcg/Day n=108 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 640 mcg/Day n=105 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (80 mcg/inhalation), twice daily for a total daily dose of 640 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	MDI 320 mcg/Day n=105 Participants Beclomethasone dipropionate metered-dose inhaler (MDI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
Count of Participants Withdrawn From Study Drug Treatment Due to Meeting Stopping Criteria for Worsening Asthma	10 Participants	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 0 to Week 6

Population: The safety analysis set included all randomly assigned patients (ITT analysis set) who received at least 1 dose of study drug. In this analysis set, treatment was assigned based on the treatment patients actually received, regardless of the treatment to which they were randomly assigned.

An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly/birth defect, or an important medical event that may not result in death, be life-threatening, or require hospitalization, but may jeopardize the patient and may require medical intervention to prevent one of the outcomes listed in this definition.

Outcome measures

Outcome measures
Measure	Placebo n=107 Participants Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 320 mcg/Day n=108 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	BAI 640 mcg/Day n=105 Participants Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (80 mcg/inhalation), twice daily for a total daily dose of 640 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.	MDI 320 mcg/Day n=105 Participants Beclomethasone dipropionate metered-dose inhaler (MDI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for 6 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 adverse event	20 Participants	22 Participants	32 Participants	32 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 mild TEAE	10 Participants	10 Participants	18 Participants	20 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 moderate TEAE	9 Participants	11 Participants	10 Participants	11 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 severe TEAE	1 Participants	1 Participants	4 Participants	1 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 treatment-related TEAE	1 Participants	2 Participants	9 Participants	4 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 serious TEAE	0 Participants	0 Participants	2 Participants	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 AE leading to withdrawal of study drug	0 Participants	1 Participants	1 Participants	0 Participants

Adverse Events

Run-in Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

BAI 320 mcg/Day

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

BAI 640 mcg/Day

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

MDI 320 mcg/Day

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Run-in Placebo n=713 participants at risk Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for up to 30 days of the single-blind Run-in Period.	Placebo n=107 participants at risk Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for the 6 weeks of the double-blind Treatment Period.	BAI 320 mcg/Day n=108 participants at risk Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for the 6 weeks of the double-blind Treatment Period.	BAI 640 mcg/Day n=105 participants at risk Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (80 mcg/inhalation), twice daily for a total daily dose of 640 mcg for the 6 weeks of the double-blind Treatment Period.	MDI 320 mcg/Day n=105 participants at risk Beclomethasone dipropionate metered-dose inhaler (MDI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for the 6 weeks of the double-blind Treatment Period.
Ear and labyrinth disorders Vertigo positional	0.00% 0/713 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/107 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/108 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.95% 1/105 • Number of events 1 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/105 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6
Infections and infestations Appendicitis	0.14% 1/713 • Number of events 1 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/107 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/108 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/105 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/105 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/713 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/107 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/108 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.95% 1/105 • Number of events 1 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/105 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6
Psychiatric disorders Suicidal behaviour	0.00% 0/713 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/107 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/108 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.95% 1/105 • Number of events 1 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	0.00% 0/105 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6

Other adverse events

Other adverse events
Measure	Run-in Placebo n=713 participants at risk Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for up to 30 days of the single-blind Run-in Period.	Placebo n=107 participants at risk Pooled breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for the 6 weeks of the double-blind Treatment Period.	BAI 320 mcg/Day n=108 participants at risk Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for the 6 weeks of the double-blind Treatment Period.	BAI 640 mcg/Day n=105 participants at risk Beclomethasone dipropionate breath-actuated inhaler (BAI), 4 inhalations (80 mcg/inhalation), twice daily for a total daily dose of 640 mcg for the 6 weeks of the double-blind Treatment Period.	MDI 320 mcg/Day n=105 participants at risk Beclomethasone dipropionate metered-dose inhaler (MDI), 4 inhalations (40 mcg/inhalation), twice daily for a total daily dose of 320 mcg for the 6 weeks of the double-blind Treatment Period.
Infections and infestations Upper respiratory tract infection	0.00% 0/713 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	2.8% 3/107 • Number of events 3 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	4.6% 5/108 • Number of events 5 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	4.8% 5/105 • Number of events 5 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6	9.5% 10/105 • Number of events 10 • Run-in Period: up to Day -30 to Day 0 Treatment Period: Day 0 to Week 6

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 1-215-591-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER