Bronchial Asthma
Conditions
Brief summary
To compare the therapeutic equivalence of Beclomethasone Dipropionate MDI (Inhalation Aerosol) 0.04 mg/ INH with the marketed QVAR® 40 mcg (Beclomethasone dipropionate hydrofluoroalkane (HFA)) and to demonstrate superiority of both active treatments over placebo.
Detailed description
This study is to demonstrate the pharmacodynamic bioequivalence of the test product to the reference product in terms of improvement in FEV1 measured before and after 4 weeks of treatment in adult patients with chronic stable asthma.
Interventions
DRUGTest Product
Beclomethasone Dipropionate Inhalation Aerosol, 40 mcg
DRUGReference Product
Beclomethasone Dipropionate Inhalation Aerosol, 40 mcg
DRUGPlacebo
Placebo Product
Sponsors
Aurobindo Pharma Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Adult male or female subjects of non-childbearing or of childbearing potential committing to consistent and correct use of an acceptable method of birth control. 2. Diagnosis of asthma as defined by the National Asthma Education and Prevention Program at least 12 months prior to screening. 3. Pre-bronchodilator FEV1 of \>45% and \<85% of predicted value during the screening visit and on the first day of treatment. 4. \>15% and \>0.20 L reversibility of FEV1 within 30 minutes following 360 mcg of albuterol inhalation (pMDI). 5. Patients should be stable on their chronic asthma treatment regimen for at least four weeks prior to enrollment. 6. Currently non-smoking; had not used tobacco products (i.e., cigarettes, cigars, pipe tobacco) within the past year, and having had \<10 pack-years of historical use. 7. Ability to replace current short-acting β agonist (SABAs) with salbutamol/albuterol inhaler for use as needed for the duration of the study. Subjects should be able to withhold all inhaled SABAs for at least six hours prior to lung function assessments on study visits. 8. Ability to discontinue their asthma medications (inhaled corticosteroids and long-acting β agonists) during the run-in period and for remainder of the study. 9. Willingness to give their written informed consent to participate in the study.
Exclusion criteria
1. Life-threatening asthma, defined as a history of asthma episodes(s) requiring intubation, and/or associated with hypercapnia, respiratory arrest or hypoxic seizures, asthma related syncopal episode(s), or hospitalizations within the past year prior to the screening or during the run-in period. 2. Significant respiratory disease other than asthma (COPD, interstitial lung disease, etc.) 3. Evidence or history of clinically significant disease or abnormality including congestive heart failure, uncontrolled hypertension, uncontrolled coronary artery disease, myocardial infarction, or cardiac dysrhythmia. In addition, historical or current evidence of significant hematologic, hepatic, neurologic, psychiatric, renal, or other diseases that, in the opinion of the investigator, would put the patient at risk through study participation, or would affect the study analyses if the disease exacerbates during the study. 4. Viral or bacterial, upper or lower respiratory tract infection, or sinus, or middle ear infection within four weeks prior to the screening, during the run-in period, or on the day of treatment. 5. Hypersensitivity to any sympathomimetic drug (e.g., albuterol) or any inhaled, intranasal, or systemic corticosteroid therapy. 6. Patients receiving β2-blockers, anti-arrhythmics, anti-depressants, and monoamine oxidase inhibitors within 4 weeks prior to the screening. 7. Patients who required systemic corticosteroids (for any reason) within the past 2 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in FEV1 From Pre Dose to End of Treatment | 4 weeks | Mean change in Forced Expiratory volume in 1 second (FEV 1) from baseline to end of study visit |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test Group Subjects randomly enrolled into test group received test comparator, Beclomethasone dipropinate, 0.04 mg/INH to administer one inhalation twice daily | 617 |
| Reference Group Subjects randomly enrolled into Reference group received Reference comparator, QVAR® containing Beclomethasone dipropinate, 0.04 mg/INH to administer one inhalation twice daily | 615 |
| Placebo Group Subjects randomly enrolled into Placebo group received a Placebo device to administer one inhalation twice daily | 308 |
| Total | 1,540 |
Baseline characteristics
| Characteristic | Test Group | Total | Placebo Group | Reference Group |
|---|---|---|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 12.71 | 41.2 years STANDARD_DEVIATION 12.8 | 40.6 years STANDARD_DEVIATION 12.86 | 41.8 years STANDARD_DEVIATION 12.85 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 617 Participants | 1540 Participants | 308 Participants | 615 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment India | 617 participants | 1540 participants | 308 participants | 615 participants |
| Sex: Female, Male Female | 267 Participants | 678 Participants | 139 Participants | 272 Participants |
| Sex: Female, Male Male | 350 Participants | 862 Participants | 169 Participants | 343 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 619 | 0 / 620 | 0 / 310 |
| other Total, other adverse events | 39 / 619 | 25 / 620 | 18 / 310 |
| serious Total, serious adverse events | 0 / 619 | 0 / 620 | 0 / 310 |
Outcome results
Primary
Change in FEV1 From Pre Dose to End of Treatment
Mean change in Forced Expiratory volume in 1 second (FEV 1) from baseline to end of study visit
Time frame: 4 weeks
Population: Mean change of FEV1 from baseline to end of study was measured
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group-I (Test) | Change in FEV1 From Pre Dose to End of Treatment | 0.23 Litres | Standard Error 0.01 |
| Group-II (Reference) | Change in FEV1 From Pre Dose to End of Treatment | 0.22 Litres | Standard Error 0.01 |
| Group-III (Placebo) | Change in FEV1 From Pre Dose to End of Treatment | 0.09 Litres | Standard Error 0.01 |