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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02031640
• Other study ID #: BDB-AS-301
• Secondary ID: 2013-003397-27
• Status: Completed
• Phase: Phase 3
• Start date: December 2013
• Est. completion date: December 2014

Study information

• Verified date: November 2021
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1113
• Est. completion date: December 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Beclomethasone dipropionate

• Placebo

• 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.

Locations

Country	Name	City	State
Germany	Teva Investigational Site 32326	Berlin
Germany	Teva Investigational Site 32332	Berlin
Germany	Teva Investigational Site 32334	Berlin
Germany	Teva Investigational Site 32331	Frankfurt
Germany	Teva Investigational Site 32335	Gelnhausen
Germany	Teva Investigational Site 32329	Leipzig
Germany	Teva Investigational Site 32330	Magdeburg
Germany	Teva Investigational Site 32333	Mainz
Germany	Teva Investigational Site 32328	Munchen
Germany	Teva Investigational Site 32327	Munich
Germany	Teva Investigational Site 32325	Rudersdorf
Hungary	Teva Investigational Site 51081	Budapest
Hungary	Teva Investigational Site 51083	Debrecen
Hungary	Teva Investigational Site 51084	Debrecen
Hungary	Teva Investigational Site 51080	Erd
Hungary	Teva Investigational Site 51108	Gyor
Hungary	Teva Investigational Site 51079	Kapuvár
Hungary	Teva Investigational Site 51109	Komárom
Hungary	Teva Investigational Site 51086	Nyíregyháza
Hungary	Teva Investigational Site 51078	Siófok
Hungary	Teva Investigational Site 51087	Szombathely
Poland	Teva Investigational Site 53121	Bialystok
Poland	Teva Investigational Site 53129	Bialystok
Poland	Teva Investigational Site 53130	Bialystok
Poland	Teva Investigational Site 53154	Gdansk
Poland	Teva Investigational Site 53155	Katowice
Poland	Teva Investigational Site 53124	Krakow
Poland	Teva Investigational Site 53125	Lodz
Poland	Teva Investigational Site 53132	Lodz
Poland	Teva Investigational Site 53126	Lubin
Poland	Teva Investigational Site 53157	Lublin
Poland	Teva Investigational Site 53122	Ostrow Wielkopolski
Poland	Teva Investigational Site 53156	Poznan
Poland	Teva Investigational Site 53123	Strzelce Opolskie
Poland	Teva Investigational Site 53127	Tarnow
Poland	Teva Investigational Site 53131	Warsaw
Poland	Teva Investigational Site 53128	Wroclaw
United States	Teva Investigational Site 10858	Albany	Georgia
United States	Teva Investigational Site 10820	Austin	Texas
United States	Teva Investigational Site 10826	Aventura	Florida
United States	Teva Investigational Site 10832	Baltimore	Maryland
United States	Teva Investigational Site 10794	Bellevue	Nebraska
United States	Teva Investigational Site 10814	Bellevue	Nebraska
United States	Teva Investigational Site 10805	Bellingham	Washington
United States	Teva Investigational Site 10850	Bethesda	Maryland
United States	Teva Investigational Site 10808	Boerne	Texas
United States	Teva Investigational Site 10846	Brick	New Jersey
United States	Teva Investigational Site 10842	Canton	Ohio
United States	Teva Investigational Site 12266	Centennial	Colorado
United States	Teva Investigational Site 10792	Cincinnati	Ohio
United States	Teva Investigational Site 10811	Cincinnati	Ohio
United States	Teva Investigational Site 10877	Clearwater	Florida
United States	Teva Investigational Site 10838	Colorado Springs	Colorado
United States	Teva Investigational Site 10869	Columbia	Missouri
United States	Teva Investigational Site 10851	Costa Mesa	California
United States	Teva Investigational Site 10830	Dallas	Texas
United States	Teva Investigational Site 10844	Denver	Colorado
United States	Teva Investigational Site 10816	Edgewater	Florida
United States	Teva Investigational Site 10831	El Paso	Texas
United States	Teva Investigational Site 10822	Eugene	Oregon
United States	Teva Investigational Site 10863	Greenfield	Wisconsin
United States	Teva Investigational Site 10849	Huntington Beach	California
United States	Teva Investigational Site 10872	Huntington Beach	California
United States	Teva Investigational Site 10809	Indianapolis	Indiana
United States	Teva Investigational Site 10795	Iowa City	Iowa
United States	Teva Investigational Site 10803	Knoxville	Tennessee
United States	Teva Investigational Site 10791	Lake Oswego	Oregon
United States	Teva Investigational Site 10862	Lawrenceville	Georgia
United States	Teva Investigational Site 10878	Live Oak	Texas
United States	Teva Investigational Site 10833	Long Beach	California
United States	Teva Investigational Site 10861	Los Angeles	California
United States	Teva Investigational Site 10836	Madison	Wisconsin
United States	Teva Investigational Site 10817	Marlton	New Jersey
United States	Teva Investigational Site 10824	Medford	Oregon
United States	Teva Investigational Site 12268	Melbourne	Florida
United States	Teva Investigational Site 10807	Miami	Florida
United States	Teva Investigational Site 10840	Miami	Florida
United States	Teva Investigational Site 12269	Miami	Florida
United States	Teva Investigational Site 10815	Minneapolis	Minnesota
United States	Teva Investigational Site 10821	Minneapolis	Minnesota
United States	Teva Investigational Site 10798	Mission Viejo	California
United States	Teva Investigational Site 12261	Missoula	Montana
United States	Teva Investigational Site 10837	North Charleston	South Carolina
United States	Teva Investigational Site 10834	North Dartmouth	Massachusetts
United States	Teva Investigational Site 10856	Ocean City	New Jersey
United States	Teva Investigational Site 10800	Oklahoma City	Oklahoma
United States	Teva Investigational Site 10853	Oklahoma City	Oklahoma
United States	Teva Investigational Site 10865	Oklahoma City	Oklahoma
United States	Teva Investigational Site 12796	Oklahoma City	Oklahoma
United States	Teva Investigational Site 10806	Orange	California
United States	Teva Investigational Site 10828	Orange	California
United States	Teva Investigational Site 12262	Orangeburg	South Carolina
United States	Teva Investigational Site 10870	Owensboro	Kentucky
United States	Teva Investigational Site 10860	Paramount	California
United States	Teva Investigational Site 10859	Philadelphia	Pennsylvania
United States	Teva Investigational Site 10810	Plano	Texas
United States	Teva Investigational Site 10835	Portland	Oregon
United States	Teva Investigational Site 10813	Rancho Mirage	California
United States	Teva Investigational Site 10796	Richmond	Virginia
United States	Teva Investigational Site 10854	Richmond	Virginia
United States	Teva Investigational Site 10829	River Forest	Illinois
United States	Teva Investigational Site 10843	Riverside	California
United States	Teva Investigational Site 10801	Rochester	New York
United States	Teva Investigational Site 10868	Rolla	Missouri
United States	Teva Investigational Site 10857	Rolling Hills Estates	California
United States	Teva Investigational Site 10867	Saint Louis	Missouri
United States	Teva Investigational Site 12271	Saint Louis	Missouri
United States	Teva Investigational Site 10797	San Antonio	Texas
United States	Teva Investigational Site 10812	San Antonio	Texas
United States	Teva Investigational Site 10847	San Diego	California
United States	Teva Investigational Site 10871	San Diego	California
United States	Teva Investigational Site 10876	San Jose	California
United States	Teva Investigational Site 10875	Sarasota	Florida
United States	Teva Investigational Site 10848	Savannah	Georgia
United States	Teva Investigational Site 10866	Seattle	Washington
United States	Teva Investigational Site 10845	Skillman	New Jersey
United States	Teva Investigational Site 10823	South Burlington	Vermont
United States	Teva Investigational Site 10793	Sugar Land	Texas
United States	Teva Investigational Site 10874	Sylvania	Ohio
United States	Teva Investigational Site 12264	Tacoma	Washington
United States	Teva Investigational Site 10855	Tallahassee	Florida
United States	Teva Investigational Site 10864	Tampa	Florida
United States	Teva Investigational Site 12265	Toledo	Ohio
United States	Teva Investigational Site 10818	Tulsa	Oklahoma
United States	Teva Investigational Site 10790	Waco	Texas
United States	Teva Investigational Site 12270	Walnut Creek	California
United States	Teva Investigational Site 10827	Warrensburg	Missouri
United States	Teva Investigational Site 12795	Warwick	Rhode Island
United States	Teva Investigational Site 10799	Wheat Ridge	Colorado
United States	Teva Investigational Site 10873	Wheaton	Maryland
United States	Teva Investigational Site 12272	White Marsh	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

United States,  Germany,  Hungary,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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) )	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).	Day 1 (baseline), Weeks 2, 4, 8, 12
Secondary	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)	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.	Baseline: Days -6 to Day 1 (pre-randomization), Treatment: Day 2 to Week 12
Secondary	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)	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.	Baseline: Days -7 to Day -1, Treatment: Day 1 to Week 12
Secondary	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)	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.	Baseline: Days -6 to Day 1 (pre-randomization), Treatment: Day 1 to Week 12
Secondary	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)	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.	Days -6 to Day 1 (pre-randomization), Treatment: Day 1 to Week 12
Secondary	Kaplan-Meier Estimates for Time to Withdrawal From Study Treatment Due to Meeting Stopping Criteria for Worsening Asthma	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.	Day 1 - Week 12
Secondary	Number of Participants Withdrawn From Study Due to Meeting Stopping Criteria for Worsening Asthma During the 12-Week Treatment Period	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.	Treatment period: Day 1 up to Week 12