A Safety and Efficacy Study of Beclomethasone Dipropionate Delivered Via Breath-Actuated Inhaler (BAI) or Metered-Dose Inhaler (MDI) in Participants >=12 Years Old With Persistent Asthma

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02031640
• Collaborator: (none)
• Enrollment: 1,113
• Locations: 131
• Arms: 5
• Duration (Months): 12
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This is a Phase 3, randomized, placebo-controlled, double-blind,double-dummy, parallel-group, 12-week study in male and female patients, 12 years of age and older, with persistent asthma.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Beclomethasone dipropionate; Drug: Placebo; Drug: Albuterol/salbutamol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1113 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Double-Dummy, Placebo Controlled, Parallel-Group, 12-Week Clinical Study to Assess the Efficacy and Safety of 320 or 640 mcg/Day of Beclomethasone Dipropionate Delivered Via Breath-Actuated Inhaler (BAI) or Metered-Dose Inhaler (MDI) in Adolescent and Adult Patients 12 Years of Age and Older With Persistent Asthma
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BDP 320 mcg BAI Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily.	Drug: Beclomethasone dipropionate; Other Names: BDP ; Drug: Placebo; Drug: Albuterol/salbutamol; Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.; Other Names: bronchodilators
Experimental: BDP 640 mcg BAI Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily.	Drug: Beclomethasone dipropionate; Other Names: BDP ; Drug: Placebo; Drug: Albuterol/salbutamol; Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.; Other Names: bronchodilators
Active Comparator: BDP 320 mcg MDI Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily.	Drug: Beclomethasone dipropionate; Other Names: BDP ; Drug: Placebo; Drug: Albuterol/salbutamol; Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.; Other Names: bronchodilators
Active Comparator: BDP 640 mcg MDI Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily.	Drug: Beclomethasone dipropionate; Other Names: BDP ; Drug: Placebo; Drug: Albuterol/salbutamol; Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.; Other Names: bronchodilators
Placebo Comparator: Placebo BAI and MDI Placebo breath-actuated inhaler (BAI), twice daily. Plus placebo metered dose inhaler (MDI), twice daily.	Drug: Placebo; Drug: Albuterol/salbutamol; Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.; Other Names: bronchodilators

Outcome Measures

Primary Outcome Measures

1. Standardized Baseline-adjusted Trough Morning Forced Expiratory Volume in 1 Second (FEV1) Area Under the Effect Curve From Time 0 to 12 Weeks (AUEC(0-12wk) ) [Day 1 (baseline), Weeks 2, 4, 8, 12]

   Trough morning FEV1 measurements were taken pre-dose and pre-rescue bronchodilator treatment for asthma. The baseline pulmonary function measurement was defined as the measurement obtained at randomization visit (Day 1). Pulmonary function measurements (including FEV1) were obtained electronically by spirometry. All pulmonary function test data were submitted to a central reading center for evaluation. The highest FEV1 value from 3 acceptable and 2 repeatable maneuvers (maximum of 5 attempts) was used. Baseline-adjusted FEV1 AUEC(0-12wk) were calculated using the trapezoidal rule. The standardized baseline-adjusted FEV1 AUEC(0-12 wk) accommodates participants who dropped out of the study. Baseline-adjusted FEV1 AUEC(0-t weeks)/t, where t =12 weeks for patients who complete the FEV1 assessment at Week 12. For participants who dropped out early, t <12 weeks (2, 4, or 8 weeks).

Secondary Outcome Measures

1. Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Over the 12-week Treatment Period Using a Mixed Model for Repeated Measures (MMRM) [Baseline: Days -6 to Day 1 (pre-randomization), Treatment: Day 2 to Week 12]

   A hand-held peak flow meter was provided to patients at the screening visit and used to determine the morning and evening PEF throughout the course of the study. Daily trough morning PEF assessments were taken pre-dose and pre-rescue bronchodilator over the 12-week treatment period. The patient recorded the highest value of 3 measurements obtained in the morning and evening in the patient diary. Baseline in trough morning PEF is defined as the average of recorded trough morning PEF assessments over the 7-day window before randomization, including the morning assessment on Day 1 before randomization. Weekly average PEF data was generated using 7-day windows based on analysis days (before the first dose of double-blind study treatment). PEF over the 12 week treatment period was performed using a mixed-model for repeated measures (MMRM) with effects due to baseline weekly average of daily trough morning PEF, sex, age, treatment, time, and time by treatment interaction.

2. Change From Baseline in Weekly Average of Daily Evening Peak Expiratory Flow (PEF) Over the 12-week Treatment Period Using a Mixed Model for Repeated Measures (MMRM) [Baseline: Days -7 to Day -1, Treatment: Day 1 to Week 12]

   A hand-held peak flow meter was provided to patients at the screening visit and used to determine the morning and evening PEF throughout the course of the study. The patient recorded the highest value of 3 measurements obtained in the morning and evening in the patient diary. Baseline in evening PEF is defined as the average of recorded evening PEF assessments over the 7-day window before randomization. Weekly average PEF data was generated using 7-day windows based on analysis days (after the first dose of double-blind study treatment). PEF over the 12 week treatment period was performed using a mixed-model for repeated measures (MMRM) with effects due to baseline weekly average of daily evening peak PEF, sex, age, treatment, time, and time by treatment interaction.

3. Change From Baseline in the Weekly Average of Total Daily (24-hour) Use of Albuterol/Salbutamol Inhalation Aerosol (Number of Inhalations) Over Weeks 1-12 Using a Mixed Model for Repeated Measures (MMRM) [Baseline: Days -6 to Day 1 (pre-randomization), Treatment: Day 1 to Week 12]

   Change from baseline in the use of rescue medication, albuterol/salbutamol, during the treatment period offers an indication of asthma control. Baseline was defined as the average of recorded daily usage of albuterol/salbutamol inhalation aerosol over the 7 days prior to the first dose of double-blind study treatment, including the morning usage at the randomization visit. Weekly average rescue medication data was generated using 7-day windows based on analysis days (after the first dose of double-blind study treatment). Weekly average over the 12 week treatment period was performed using a mixed-model for repeated measures (MMRM) with effects due to baseline value, sex, age, time, treatment, and time-by-treatment interaction.

4. Change From Baseline in the Weekly Average of the Total Daily Asthma Symptom Score Over Weeks 1-12 Using a Mixed Model for Repeated Measures (MMRM) [Days -6 to Day 1 (pre-randomization), Treatment: Day 1 to Week 12]

   Asthma symptom scores are recorded in the patient's diary each morning and each evening before determining PEF and before administration of study or rescue medications. The Daytime Symptom Score (determined in the evening) has a range from 0=No symptoms during the day to 5=Symptoms so severe that I could not go to work or perform normal daily activities. The Nighttime Symptom Score (determined in the morning) has a range from 0=No symptoms during the night to 4=Symptoms so severe that I did not sleep at all. The total daily asthma symptom score is the average of the daytime and the nighttime scores (full scale is 0 - 4.5). The total daily asthma symptom score is missing if either the daytime or nighttime score is missing. Baseline was the average of recorded daily asthma symptom scores over 7 days prior to the first dose of study treatment. The weekly average was the sum of total daily asthma symptom scores over the 7 days divided by the number of non-missing assessments.

5. Kaplan-Meier Estimates for Time to Withdrawal From Study Treatment Due to Meeting Stopping Criteria for Worsening Asthma [Day 1 - Week 12]

   Time to withdrawal due to meeting stopping criteria is defined as number of days elapsed from the date of the first dose of double-blind study treatment to the date of withdrawal due to meeting stopping criteria. Stopping criteria are: FEV1 as measured at the study center is below the FEV1 stability limit value calculated at RV. Based upon review of patient diary data, the patient has experienced any of the following during any 7-day period: 4+ days in which the highest (of 3 efforts) am PEF fall below the PEF stability limit calculated when randomized. The patient meets with the investigator who determines whether the FEV1 is consistent with worsening asthma; 3+ days in which 12+ inhalations/day of rescue medication were used 2+ days in which the patient experienced a nighttime asthma symptom score of more than 2 Clinical asthma exacerbation requiring (for example) the use of systemic corticosteroids, or the emergency room or hospitalization.

6. Number of Participants Withdrawn From Study Due to Meeting Stopping Criteria for Worsening Asthma During the 12-Week Treatment Period [Treatment period: Day 1 up to Week 12]

   A count of participants who were withdrawn from the study due to meeting stopping criteria. Alert criteria for individual patients with worsening asthma were designed to ensure patient safety. The investigator determined whether the patient's overall clinical picture is 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 alert criteria is: FEV1 as measured at the study center is below the FEV1 stability limit value calculated at randomization visit (Day 1). Other criteria as defined in the protocol.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Severity of disease: The patient has persistent asthma, with a forced expiratory volume in 1 second (FEV1) 40%-85% of the value predicted for age, height, sex, and race as per the National Health and Nutrition Examination Survey (NHANES III) (Hankinson et al 1999) reference values at screening visit.

• Current asthma therapy: The patient must be on a stable dose of an inhaled corticosteroid (ICS) of at least 440 mcg/day of fluticasone propionate or equivalent for a minimum of 4 weeks before screening visit, or any inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) combination for a minimum of 4 weeks before the prescreening visit.

• Reversibility of disease: The patient has demonstrated at least 12% reversibility of FEV1 and at least 200 mL increase from baseline FEV1 (patients age 18 and older) within 30 minutes after 2-4 inhalations of albuterol/salbutamol hydrofluoroalkane (HFA) MDI (90 mcg ex-actuator) or equivalent at the screening visit

• If female, the patient is currently not pregnant, breast feeding, or attempting to become pregnant. If of childbearing potential, has a negative serum pregnancy test and is willing to commit to using a consistent and acceptable method of birth control.

• Other criteria apply, please contact the investigator for more information

Exclusion Criteria:

• The patient has a history of life-threatening asthma, defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest, or hypoxic seizures.

• The patient is pregnant or lactating, or plans to become pregnant during the study period or for 30 days after the patient's last study-related visit (for eligible patients only, if applicable). Eligible female patients unwilling to employ appropriate contraceptive measures to ensure that pregnancy will not occur during the study will be excluded. Any patient becoming pregnant during the study will be withdrawn from the study.

• The patient has a known hypersensitivity to any corticosteroid or any of the excipients in the study drug or rescue medication formulation.

• The patient currently smokes or has a smoking history of 10 pack-years or more (a pack-year is defined as smoking 1 pack of cigarettes/day for 1 year).

• The patient has had an asthma exacerbation requiring oral corticosteroids within 30 days before the screening visit, or has had any hospitalization for asthma within 2 months before the screening visit.

• The patient has historical or current evidence of a clinically significant disease. Significant disease is defined as any disease that in the medical judgment of the investigator would put the safety of the patient at risk through participation or that could affect the efficacy or safety analysis if the disease/condition worsened during the study.

• Other criteria apply, please contact the investigator for more information

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 10851	Costa Mesa	California	United States
2	Teva Investigational Site 10849	Huntington Beach	California	United States
3	Teva Investigational Site 10872	Huntington Beach	California	United States
4	Teva Investigational Site 10833	Long Beach	California	United States
5	Teva Investigational Site 10861	Los Angeles	California	United States
6	Teva Investigational Site 10798	Mission Viejo	California	United States
7	Teva Investigational Site 10806	Orange	California	United States
8	Teva Investigational Site 10828	Orange	California	United States
9	Teva Investigational Site 10860	Paramount	California	United States
10	Teva Investigational Site 10813	Rancho Mirage	California	United States
11	Teva Investigational Site 10843	Riverside	California	United States
12	Teva Investigational Site 10857	Rolling Hills Estates	California	United States
13	Teva Investigational Site 10847	San Diego	California	United States
14	Teva Investigational Site 10871	San Diego	California	United States
15	Teva Investigational Site 10876	San Jose	California	United States
16	Teva Investigational Site 12270	Walnut Creek	California	United States
17	Teva Investigational Site 12266	Centennial	Colorado	United States
18	Teva Investigational Site 10838	Colorado Springs	Colorado	United States
19	Teva Investigational Site 10844	Denver	Colorado	United States
20	Teva Investigational Site 10799	Wheat Ridge	Colorado	United States
21	Teva Investigational Site 10826	Aventura	Florida	United States
22	Teva Investigational Site 10877	Clearwater	Florida	United States
23	Teva Investigational Site 10816	Edgewater	Florida	United States
24	Teva Investigational Site 12268	Melbourne	Florida	United States
25	Teva Investigational Site 10807	Miami	Florida	United States
26	Teva Investigational Site 10840	Miami	Florida	United States
27	Teva Investigational Site 12269	Miami	Florida	United States
28	Teva Investigational Site 10875	Sarasota	Florida	United States
29	Teva Investigational Site 10855	Tallahassee	Florida	United States
30	Teva Investigational Site 10864	Tampa	Florida	United States
31	Teva Investigational Site 10858	Albany	Georgia	United States
32	Teva Investigational Site 10862	Lawrenceville	Georgia	United States
33	Teva Investigational Site 10848	Savannah	Georgia	United States
34	Teva Investigational Site 10829	River Forest	Illinois	United States
35	Teva Investigational Site 10809	Indianapolis	Indiana	United States
36	Teva Investigational Site 10795	Iowa City	Iowa	United States
37	Teva Investigational Site 10870	Owensboro	Kentucky	United States
38	Teva Investigational Site 10832	Baltimore	Maryland	United States
39	Teva Investigational Site 10850	Bethesda	Maryland	United States
40	Teva Investigational Site 10873	Wheaton	Maryland	United States
41	Teva Investigational Site 12272	White Marsh	Maryland	United States
42	Teva Investigational Site 10834	North Dartmouth	Massachusetts	United States
43	Teva Investigational Site 10815	Minneapolis	Minnesota	United States
44	Teva Investigational Site 10821	Minneapolis	Minnesota	United States
45	Teva Investigational Site 10869	Columbia	Missouri	United States
46	Teva Investigational Site 10868	Rolla	Missouri	United States
47	Teva Investigational Site 10867	Saint Louis	Missouri	United States
48	Teva Investigational Site 12271	Saint Louis	Missouri	United States
49	Teva Investigational Site 10827	Warrensburg	Missouri	United States
50	Teva Investigational Site 12261	Missoula	Montana	United States
51	Teva Investigational Site 10794	Bellevue	Nebraska	United States
52	Teva Investigational Site 10814	Bellevue	Nebraska	United States
53	Teva Investigational Site 10846	Brick	New Jersey	United States
54	Teva Investigational Site 10817	Marlton	New Jersey	United States
55	Teva Investigational Site 10856	Ocean City	New Jersey	United States
56	Teva Investigational Site 10845	Skillman	New Jersey	United States
57	Teva Investigational Site 10801	Rochester	New York	United States
58	Teva Investigational Site 10842	Canton	Ohio	United States
59	Teva Investigational Site 10792	Cincinnati	Ohio	United States
60	Teva Investigational Site 10811	Cincinnati	Ohio	United States
61	Teva Investigational Site 10874	Sylvania	Ohio	United States
62	Teva Investigational Site 12265	Toledo	Ohio	United States
63	Teva Investigational Site 10800	Oklahoma City	Oklahoma	United States
64	Teva Investigational Site 10853	Oklahoma City	Oklahoma	United States
65	Teva Investigational Site 10865	Oklahoma City	Oklahoma	United States
66	Teva Investigational Site 12796	Oklahoma City	Oklahoma	United States
67	Teva Investigational Site 10818	Tulsa	Oklahoma	United States
68	Teva Investigational Site 10822	Eugene	Oregon	United States
69	Teva Investigational Site 10791	Lake Oswego	Oregon	United States
70	Teva Investigational Site 10824	Medford	Oregon	United States
71	Teva Investigational Site 10835	Portland	Oregon	United States
72	Teva Investigational Site 10859	Philadelphia	Pennsylvania	United States
73	Teva Investigational Site 12795	Warwick	Rhode Island	United States
74	Teva Investigational Site 10837	North Charleston	South Carolina	United States
75	Teva Investigational Site 12262	Orangeburg	South Carolina	United States
76	Teva Investigational Site 10803	Knoxville	Tennessee	United States
77	Teva Investigational Site 10820	Austin	Texas	United States
78	Teva Investigational Site 10808	Boerne	Texas	United States
79	Teva Investigational Site 10830	Dallas	Texas	United States
80	Teva Investigational Site 10831	El Paso	Texas	United States
81	Teva Investigational Site 10878	Live Oak	Texas	United States
82	Teva Investigational Site 10810	Plano	Texas	United States
83	Teva Investigational Site 10797	San Antonio	Texas	United States
84	Teva Investigational Site 10812	San Antonio	Texas	United States
85	Teva Investigational Site 10793	Sugar Land	Texas	United States
86	Teva Investigational Site 10790	Waco	Texas	United States
87	Teva Investigational Site 10823	South Burlington	Vermont	United States
88	Teva Investigational Site 10796	Richmond	Virginia	United States
89	Teva Investigational Site 10854	Richmond	Virginia	United States
90	Teva Investigational Site 10805	Bellingham	Washington	United States
91	Teva Investigational Site 10866	Seattle	Washington	United States
92	Teva Investigational Site 12264	Tacoma	Washington	United States
93	Teva Investigational Site 10863	Greenfield	Wisconsin	United States
94	Teva Investigational Site 10836	Madison	Wisconsin	United States
95	Teva Investigational Site 32326	Berlin		Germany
96	Teva Investigational Site 32332	Berlin		Germany
97	Teva Investigational Site 32334	Berlin		Germany
98	Teva Investigational Site 32331	Frankfurt		Germany
99	Teva Investigational Site 32335	Gelnhausen		Germany
100	Teva Investigational Site 32329	Leipzig		Germany
101	Teva Investigational Site 32330	Magdeburg		Germany
102	Teva Investigational Site 32333	Mainz		Germany
103	Teva Investigational Site 32328	Munchen		Germany
104	Teva Investigational Site 32327	Munich		Germany
105	Teva Investigational Site 32325	Rudersdorf		Germany
106	Teva Investigational Site 51081	Budapest		Hungary
107	Teva Investigational Site 51083	Debrecen		Hungary
108	Teva Investigational Site 51084	Debrecen		Hungary
109	Teva Investigational Site 51080	Erd		Hungary
110	Teva Investigational Site 51108	Győr		Hungary
111	Teva Investigational Site 51079	Kapuvár		Hungary
112	Teva Investigational Site 51109	Komárom		Hungary
113	Teva Investigational Site 51086	Nyíregyháza		Hungary
114	Teva Investigational Site 51078	Siófok		Hungary
115	Teva Investigational Site 51087	Szombathely		Hungary
116	Teva Investigational Site 53121	Bialystok		Poland
117	Teva Investigational Site 53129	Bialystok		Poland
118	Teva Investigational Site 53130	Białystok		Poland
119	Teva Investigational Site 53154	Gdansk		Poland
120	Teva Investigational Site 53155	Katowice		Poland
121	Teva Investigational Site 53124	Krakow		Poland
122	Teva Investigational Site 53125	Lodz		Poland
123	Teva Investigational Site 53132	Lodz		Poland
124	Teva Investigational Site 53126	Lubin		Poland
125	Teva Investigational Site 53157	Lublin		Poland
126	Teva Investigational Site 53122	Ostrow Wielkopolski		Poland
127	Teva Investigational Site 53156	Poznan		Poland
128	Teva Investigational Site 53123	Strzelce Opolskie		Poland
129	Teva Investigational Site 53127	Tarnow		Poland
130	Teva Investigational Site 53131	Warsaw		Poland
131	Teva Investigational Site 53128	Wroclaw		Poland

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT02031640
• Other Study ID Numbers: BDB-AS-301; 2013-003397-27
• First Posted: Jan 9, 2014
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.: asthma; breath-actuated inhaler; metered-dose inhaler
• Additional relevant MeSH terms: Asthma; Beclomethasone; Albuterol; Bronchodilator Agents

Study Results

Participant Flow

Recruitment Details	For this study, 125 sites were activated, 115 sites screened at least 1 patient (91 centers in the United States, 10 centers in Germany, 10 centers in Hungary, and 4 centers in Poland), and 97 sites randomized at least 1 patient.
Pre-assignment Detail	There were two periods prior to treatment assignment: a screening period and a run-in period.

Arm/Group Title	Consented Patients - Standard ICS and Placebo	Placebo BAI and MDI	BDP 320 mcg BAI	BDP 640 mcg BAI	BDP 320 mcg MDI	BDP 640 mcg MDI
Arm/Group Description	Consented patients were placed on a standard inhaled corticosteroids (ICS) of fluticasone propionate through the Screening and Run-In Periods. The assigned total daily dose was 440 mcg/day or 880 mcg/day dependent upon prestudy asthma treatment. In addition to standard ICS, participants were provided with single-blind placebo BAI and single-blind placebo MDI device for twice-daily use during the Run-In period. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms	Placebo breath-actuated inhaler (BAI), twice daily. Plus placebo metered dose inhaler (MDI), twice daily. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms.
Period Title: Screening Period
STARTED	1113	0	0	0	0	0
COMPLETED	701	0	0	0	0	0
NOT COMPLETED	412	0	0	0	0	0
Period Title: Screening Period
STARTED	701	0	0	0	0	0
COMPLETED	532	0	0	0	0	0
NOT COMPLETED	169	0	0	0	0	0
Period Title: Screening Period
STARTED	0	106	106	106	107	107
Full Analysis Set	0	106	104	106	106	107
COMPLETED	0	84	100	99	96	104
NOT COMPLETED	0	22	6	7	11	3

Baseline Characteristics

Arm/Group Title	Placebo BAI and MDI	BDP 320 mcg BAI	BDP 640 mcg BAI	BDP 320 mcg MDI	BDP 640 mcg MDI	Total
Arm/Group Description	Placebo breath-actuated inhaler (BAI), twice daily. Plus placebo metered dose inhaler (MDI), twice daily. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Albuterol/salbutamol: Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Total of all reporting groups
Overall Participants	106	106	106	107	107	532
Age (Count of Participants)
<=18 years	4 3.8%	5 4.7%	7 6.6%	4 3.7%	6 5.6%	26 4.9%
Between 18 and 65 years	94 88.7%	86 81.1%	92 86.8%	93 86.9%	92 86%	457 85.9%
>=65 years	8 7.5%	15 14.2%	7 6.6%	10 9.3%	9 8.4%	49 9.2%
Sex: Female, Male (Count of Participants)
Female	68 64.2%	69 65.1%	67 63.2%	65 60.7%	66 61.7%	335 63%
Male	38 35.8%	37 34.9%	39 36.8%	42 39.3%	41 38.3%	197 37%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	6 5.7%	3 2.8%	5 4.7%	2 1.9%	2 1.9%	18 3.4%
Black or African American	27 25.5%	18 17%	14 13.2%	16 15%	24 22.4%	99 18.6%
White	73 68.9%	85 80.2%	87 82.1%	89 83.2%	81 75.7%	415 78%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Standardized Baseline-adjusted Trough Morning Forced Expiratory Volume in 1 Second (FEV1) Area Under the Effect Curve From Time 0 to 12 Weeks (AUEC(0-12wk) )
Description	Trough morning FEV1 measurements were taken pre-dose and pre-rescue bronchodilator treatment for asthma. The baseline pulmonary function measurement was defined as the measurement obtained at randomization visit (Day 1). Pulmonary function measurements (including FEV1) were obtained electronically by spirometry. All pulmonary function test data were submitted to a central reading center for evaluation. The highest FEV1 value from 3 acceptable and 2 repeatable maneuvers (maximum of 5 attempts) was used. Baseline-adjusted FEV1 AUEC(0-12wk) were calculated using the trapezoidal rule. The standardized baseline-adjusted FEV1 AUEC(0-12 wk) accommodates participants who dropped out of the study. Baseline-adjusted FEV1 AUEC(0-t weeks)/t, where t =12 weeks for patients who complete the FEV1 assessment at Week 12. For participants who dropped out early, t <12 weeks (2, 4, or 8 weeks).
Time Frame	Day 1 (baseline), Weeks 2, 4, 8, 12

Outcome Measure Data

Analysis Population Description

Full analysis set- randomized patients with at least 1 dose of drug and 1 postbaseline trough am FEV1

Arm/Group Title	Placebo BAI and MDI	BDP 320 mcg BAI	BDP 640 mcg BAI	BDP 320 mcg MDI	BDP 640 mcg MDI
Arm/Group Description	Placebo breath-actuated inhaler (BAI), twice daily. Plus placebo metered dose inhaler (MDI), twice daily. Albuterol/salbutamol: Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Albuterol/salbutamol: Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Albuterol/salbutamol: Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Albuterol/salbutamol: Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Albuterol/salbutamol: Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.
Measure Participants	105	104	106	106	107
Least Squares Mean (Standard Error) [Liters]	0.056 (0.0219)	0.09 (0.0221)	0.101 (0.0221)	0.041 (0.0217)	0.096 (0.0216)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 320 mcg BAI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.272
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean (LSM) Difference
	Estimated Value	0.034
	Confidence Interval	(2-Sided) 95%; -0.027 to 0.095
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 640 mcg BAI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1415
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.045
	Confidence Interval	(2-Sided) 95%; -0.015 to 0.106
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 320 mcg MDI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6356
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.015
	Confidence Interval	(2-Sided) 95%; -0.075 to 0.046
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 640 mcg MDI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1932
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Over the 12-week Treatment Period Using a Mixed Model for Repeated Measures (MMRM)
Description	A hand-held peak flow meter was provided to patients at the screening visit and used to determine the morning and evening PEF throughout the course of the study. Daily trough morning PEF assessments were taken pre-dose and pre-rescue bronchodilator over the 12-week treatment period. The patient recorded the highest value of 3 measurements obtained in the morning and evening in the patient diary. Baseline in trough morning PEF is defined as the average of recorded trough morning PEF assessments over the 7-day window before randomization, including the morning assessment on Day 1 before randomization. Weekly average PEF data was generated using 7-day windows based on analysis days (before the first dose of double-blind study treatment). PEF over the 12 week treatment period was performed using a mixed-model for repeated measures (MMRM) with effects due to baseline weekly average of daily trough morning PEF, sex, age, treatment, time, and time by treatment interaction.
Time Frame	Baseline: Days -6 to Day 1 (pre-randomization), Treatment: Day 2 to Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Placebo BAI and MDI	BDP 320 mcg BAI	BDP 640 mcg BAI	BDP 320 mcg MDI	BDP 640 mcg MDI
Arm/Group Description	Placebo breath-actuated inhaler (BAI), twice daily. Plus placebo metered dose inhaler (MDI), twice daily. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Albuterol/salbutamol: Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.
Measure Participants	106	104	106	106	107
Least Squares Mean (Standard Error) [Liters/minute]	-5.524 (2.5944)	5.092 (2.5625)	2.895 (2.559)	0.480 (2.558)	6.988 (2.5298)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 320 mcg BAI
	Comments
	Type of Statistical Test	Other
	Comments	The analysis of change from baseline in weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF over the 12-week treatment period was performed using a repeated measures mixed model with effects due to baseline weekly average of daily trough morning PEF, sex, age, treatment, time, and time-by-treatment interaction.
Statistical Test of Hypothesis	p-Value	0.0036
	Comments
	Method	Mixed Model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	10.616
	Confidence Interval	(2-Sided) 95%; 3.489 to 17.744
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 640 mcg BAI
	Comments	The analysis of change from baseline in weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF over the 12-week treatment period was performed using a repeated measures mixed model with effects due to baseline weekly average of daily trough morning PEF, sex, age, treatment, time, and time-by-treatment interaction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0204
	Comments
	Method	Mixed Model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	8.419
	Confidence Interval	(2-Sided) 95%; 1.309 to 15.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 320 mcg MDI
	Comments	The analysis of change from baseline in weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF over the 12-week treatment period was performed using a repeated measures mixed model with effects due to baseline weekly average of daily trough morning PEF, sex, age, treatment, time, and time-by-treatment interaction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0984
	Comments
	Method	Mixed Model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	6.004
	Confidence Interval	(2-Sided) 95%; -1.121 to 13.129
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 640 mcg BAI
	Comments	The analysis of change from baseline in weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF over the 12-week treatment period was performed using a repeated measures mixed model with effects due to baseline weekly average of daily trough morning PEF, sex, age, treatment, time, and time-by-treatment interaction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Mixed Model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	12.512
	Confidence Interval	(2-Sided) 95%; 5.435 to 19.589
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Weekly Average of Daily Evening Peak Expiratory Flow (PEF) Over the 12-week Treatment Period Using a Mixed Model for Repeated Measures (MMRM)
Description	A hand-held peak flow meter was provided to patients at the screening visit and used to determine the morning and evening PEF throughout the course of the study. The patient recorded the highest value of 3 measurements obtained in the morning and evening in the patient diary. Baseline in evening PEF is defined as the average of recorded evening PEF assessments over the 7-day window before randomization. Weekly average PEF data was generated using 7-day windows based on analysis days (after the first dose of double-blind study treatment). PEF over the 12 week treatment period was performed using a mixed-model for repeated measures (MMRM) with effects due to baseline weekly average of daily evening peak PEF, sex, age, treatment, time, and time by treatment interaction.
Time Frame	Baseline: Days -7 to Day -1, Treatment: Day 1 to Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Placebo BAI and MDI	BDP 320 mcg BAI	BDP 640 mcg BAI	BDP 320 mcg MDI	BDP 640 mcg MDI
Arm/Group Description	Placebo breath-actuated inhaler (BAI), twice daily. Plus placebo metered dose inhaler (MDI), twice daily. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.
Measure Participants	106	104	106	106	107
Least Squares Mean (Standard Error) [Liters/minute]	-4.708 (2.6503)	4.439 (2.6199)	4.462 (2.6092)	-0.62 (2.6145)	5.594 (2.5848)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 320 mcg BAI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0139
	Comments
	Method	Mixed Model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	9.147
	Confidence Interval	(2-Sided) 95%; 1.866 to 16.429
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 640 mcg BAI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0133
	Comments
	Method	Mixed Model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	9.17
	Confidence Interval	(2-Sided) 95%; 1.914 to 16.425
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 320 mcg MDI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2704
	Comments
	Method	Mixed Model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	4.088
	Confidence Interval	(2-Sided) 95%; -3.191 to 11.367
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 640 mcg MDI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0053
	Comments
	Method	Mixed Model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	10.301
	Confidence Interval	(2-Sided) 95%; 3.073 to 17.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in the Weekly Average of Total Daily (24-hour) Use of Albuterol/Salbutamol Inhalation Aerosol (Number of Inhalations) Over Weeks 1-12 Using a Mixed Model for Repeated Measures (MMRM)
Description	Change from baseline in the use of rescue medication, albuterol/salbutamol, during the treatment period offers an indication of asthma control. Baseline was defined as the average of recorded daily usage of albuterol/salbutamol inhalation aerosol over the 7 days prior to the first dose of double-blind study treatment, including the morning usage at the randomization visit. Weekly average rescue medication data was generated using 7-day windows based on analysis days (after the first dose of double-blind study treatment). Weekly average over the 12 week treatment period was performed using a mixed-model for repeated measures (MMRM) with effects due to baseline value, sex, age, time, treatment, and time-by-treatment interaction.
Time Frame	Baseline: Days -6 to Day 1 (pre-randomization), Treatment: Day 1 to Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Placebo BAI and MDI	BDP 320 mcg BAI	BDP 640 mcg BAI	BDP 320 mcg MDI	BDP 640 mcg MDI
Arm/Group Description	Placebo breath-actuated inhaler (BAI), twice daily. Plus placebo metered dose inhaler (MDI), twice daily. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.
Measure Participants	101	96	99	97	101
Least Squares Mean (Standard Error) [number of inhalations]	0.478 (0.1232)	-0.226 (0.1235)	-0.213 (0.1221)	-0.173 (0.1246)	-0.323 (0.1206)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 320 mcg BAI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.703
	Confidence Interval	(2-Sided) 95%; -1.044 to -0.363
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 640 mcg BAI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.691
	Confidence Interval	(2-Sided) 95%; -1.029 to -0.352
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 320 mcg MDI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.651
	Confidence Interval	(2-Sided) 95%; -0.994 to -0.309
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 640 mcg MDI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-0.801
	Confidence Interval	(2-Sided) 95%; -1.138 to -0.464
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in the Weekly Average of the Total Daily Asthma Symptom Score Over Weeks 1-12 Using a Mixed Model for Repeated Measures (MMRM)
Description	Asthma symptom scores are recorded in the patient's diary each morning and each evening before determining PEF and before administration of study or rescue medications. The Daytime Symptom Score (determined in the evening) has a range from 0=No symptoms during the day to 5=Symptoms so severe that I could not go to work or perform normal daily activities. The Nighttime Symptom Score (determined in the morning) has a range from 0=No symptoms during the night to 4=Symptoms so severe that I did not sleep at all. The total daily asthma symptom score is the average of the daytime and the nighttime scores (full scale is 0 - 4.5). The total daily asthma symptom score is missing if either the daytime or nighttime score is missing. Baseline was the average of recorded daily asthma symptom scores over 7 days prior to the first dose of study treatment. The weekly average was the sum of total daily asthma symptom scores over the 7 days divided by the number of non-missing assessments.
Time Frame	Days -6 to Day 1 (pre-randomization), Treatment: Day 1 to Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set. Analysis used a MMRM with effects due to baseline score, sex, age, time, treatment, and time-by-treatment interaction.

Arm/Group Title	Placebo BAI and MDI	BDP 320 mcg BAI	BDP 640 mcg BAI	BDP 320 mcg MDI	BDP 640 mcg MDI
Arm/Group Description	Placebo breath-actuated inhaler (BAI), twice daily. Plus placebo metered dose inhaler (MDI), twice daily. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.
Measure Participants	106	104	106	106	107
Least Squares Mean (Standard Error) [units on a scale]	-0.058 (0.0425)	-0.207 (0.0417)	-0.159 (0.0415)	-0.247 (0.0417)	-0.274 (0.0411)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 320 mcg BAI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0119
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.149
	Confidence Interval	(2-Sided) 95%; -0.265 to -0.033
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 640 mcg BAI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0854
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.102
	Confidence Interval	(2-Sided) 95%; -0.217 to 0.014
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 320 mcg MDI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.189
	Confidence Interval	(2-Sided) 95%; -0.306 to -0.072
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo BAI and MDI, BDP 640 mcg MDI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.216
	Confidence Interval	(2-Sided) 95%; -0.332 to -0.101
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Kaplan-Meier Estimates for Time to Withdrawal From Study Treatment Due to Meeting Stopping Criteria for Worsening Asthma
Description	Time to withdrawal due to meeting stopping criteria is defined as number of days elapsed from the date of the first dose of double-blind study treatment to the date of withdrawal due to meeting stopping criteria. Stopping criteria are: FEV1 as measured at the study center is below the FEV1 stability limit value calculated at RV. Based upon review of patient diary data, the patient has experienced any of the following during any 7-day period: 4+ days in which the highest (of 3 efforts) am PEF fall below the PEF stability limit calculated when randomized. The patient meets with the investigator who determines whether the FEV1 is consistent with worsening asthma; 3+ days in which 12+ inhalations/day of rescue medication were used 2+ days in which the patient experienced a nighttime asthma symptom score of more than 2 Clinical asthma exacerbation requiring (for example) the use of systemic corticosteroids, or the emergency room or hospitalization.
Time Frame	Day 1 - Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set; unable to calculate as few patients met stopping criteria

Arm/Group Title	Placebo BAI or MDI	BDP 320 mcg BAI	BDP 640 mcg BAI	BDP 320 mcg MDI	BDP 640 mcg MDI
Arm/Group Description	Placebo breath-actuated inhaler (BAI), twice daily. Plus placebo metered dose inhaler (MDI), twice daily. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.
Measure Participants	106	104	106	106	107
Median (95% Confidence Interval) [days]	NA	NA	NA	NA	NA

7. Secondary Outcome

Title	Number of Participants Withdrawn From Study Due to Meeting Stopping Criteria for Worsening Asthma During the 12-Week Treatment Period
Description	A count of participants who were withdrawn from the study due to meeting stopping criteria. Alert criteria for individual patients with worsening asthma were designed to ensure patient safety. The investigator determined whether the patient's overall clinical picture is 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 alert criteria is: FEV1 as measured at the study center is below the FEV1 stability limit value calculated at randomization visit (Day 1). Other criteria as defined in the protocol.
Time Frame	Treatment period: Day 1 up to Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Placebo BAI or MDI	BDP 320 mcg BAI	BDP 640 mcg BAI	BDP 320 mcg MDI	BDP 640 mcg MDI
Arm/Group Description	Placebo breath-actuated inhaler (BAI), twice daily. Plus placebo metered dose inhaler (MDI), twice daily. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.	Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.
Measure Participants	106	104	106	106	107
Count of Participants [Participants]	15 14.2%	3 2.8%	3 2.8%	5 4.7%	1 0.9%

Adverse Events

Time Frame	- Run-In Period: Days -21 to Day 1 - Double-blind Treatment Period: Day 1 to Week 12
Arm/Group Title	BDP 320 mcg BAI		BAI 640 mcg/Day		MDI 320 mcg/Day		MDI 640 mcg/Day		Placebo BAI and MDI		Run-in Period Experience for Randomized Participants
Arm/Group Description	Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms.		Beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily. Placebo MDI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms.		Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms.		Beclomethasone dipropionate (BDP) via metered dose inhaler (MDI) twice daily. Placebo BAI for blinding. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms.		Placebo breath-actuated inhaler (BAI), twice daily. Plus placebo metered dose inhaler (MDI), twice daily. Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms.		Experience of randomized participants during the Run-In Period when they were administered standard ICS (fluticasone propionate) as well as single-blind placebo BAI and single-blind placebo MDI devices for twice-daily use.
All Cause Mortality
	BDP 320 mcg BAI		BAI 640 mcg/Day		MDI 320 mcg/Day		MDI 640 mcg/Day		Placebo BAI and MDI		Run-in Period Experience for Randomized Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/106 (0%)		0/106 (0%)		0/107 (0%)		0/107 (0%)		0/106 (0%)		0/532 (0%)
Serious Adverse Events
	BDP 320 mcg BAI		BAI 640 mcg/Day		MDI 320 mcg/Day		MDI 640 mcg/Day		Placebo BAI and MDI		Run-in Period Experience for Randomized Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/106 (0.9%)		1/106 (0.9%)		1/107 (0.9%)		2/107 (1.9%)		0/106 (0%)		1/532 (0.2%)
Gastrointestinal disorders
Abdominal pain	0/106 (0%)	0	0/106 (0%)	0	1/107 (0.9%)	1	0/107 (0%)	0	0/106 (0%)	0	0/532 (0%)	0
Diverticular perforation	0/106 (0%)	0	0/106 (0%)	0	0/107 (0%)	0	1/107 (0.9%)	1	0/106 (0%)	0	0/532 (0%)	0
Gastric disorder	0/106 (0%)	0	0/106 (0%)	0	1/107 (0.9%)	1	0/107 (0%)	0	0/106 (0%)	0	0/532 (0%)	0
Pancreatitis acute	0/106 (0%)	0	0/106 (0%)	0	1/107 (0.9%)	1	0/107 (0%)	0	0/106 (0%)	0	0/532 (0%)	0
General disorders
Non-cardiac chest pain	0/106 (0%)	0	0/106 (0%)	0	0/107 (0%)	0	0/107 (0%)	0	0/106 (0%)	0	1/532 (0.2%)	1
Hepatobiliary disorders
Cholelithiasis	0/106 (0%)	0	0/106 (0%)	0	1/107 (0.9%)	1	0/107 (0%)	0	0/106 (0%)	0	0/532 (0%)	0
Infections and infestations
Gastroenteritis	1/106 (0.9%)	1	0/106 (0%)	0	0/107 (0%)	0	0/107 (0%)	0	0/106 (0%)	0	0/532 (0%)	0
Pharyngeal abscess	0/106 (0%)	0	0/106 (0%)	0	0/107 (0%)	0	1/107 (0.9%)	1	0/106 (0%)	0	0/532 (0%)	0
Metabolism and nutrition disorders
Hypokalaemia	1/106 (0.9%)	1	0/106 (0%)	0	0/107 (0%)	0	0/107 (0%)	0	0/106 (0%)	0	0/532 (0%)	0
Renal and urinary disorders
Renal failure acute	1/106 (0.9%)	1	0/106 (0%)	0	0/107 (0%)	0	0/107 (0%)	0	0/106 (0%)	0	0/532 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/106 (0%)	0	1/106 (0.9%)	1	0/107 (0%)	0	0/107 (0%)	0	0/106 (0%)	0	0/532 (0%)	0
Other (Not Including Serious) Adverse Events
	BDP 320 mcg BAI		BAI 640 mcg/Day		MDI 320 mcg/Day		MDI 640 mcg/Day		Placebo BAI and MDI		Run-in Period Experience for Randomized Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/106 (8.5%)		11/106 (10.4%)		9/107 (8.4%)		12/107 (11.2%)		2/106 (1.9%)		8/532 (1.5%)
Infections and infestations
Oral candidiasis	5/106 (4.7%)	7	10/106 (9.4%)	12	3/107 (2.8%)	3	9/107 (8.4%)	11	0/106 (0%)	0	7/532 (1.3%)	7
Upper respiratory tract infection	4/106 (3.8%)	4	1/106 (0.9%)	1	7/107 (6.5%)	7	4/107 (3.7%)	4	2/106 (1.9%)	2	1/532 (0.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.