Asthma
Conditions
Brief summary
To Evaluate the Pharmacodynamic Equivalence of Albuterol Sulfate Inhalation Aerosol, eq 90 mcg base (Sun Pharmaceuticals Industries Limited) to PROAIR® HFA (albuterol sulfate) Inhalation Aerosol, eq 90 mcg base (Teva Respiratory, LLC) in Subjects With Stable, Mild Asthma
Interventions
DRUGZero-dose
Treatment A
DRUG90 mcg of PROAIR® HFA
Treatment B
DRUG180 mcg of 90 mcg of PROAIR® HFA
Treatment C
DRUG90 mcg of albuterol sulfate inhalation aerosol
Treatment D
Sponsors
Sun Pharmaceutical Industries Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Men or non-pregnant women 18 to 65 years of age. 2. Signed informed consent form that meets all criteria of current Food and Drug Administration (FDA) regulations. 3. Females of childbearing potential must not be pregnant or lactating (as confirmed by a negative urine pregnancy test 4. Ability to use inhalation aerosol correctly.
Exclusion criteria
1. Any clinically significant finding on physical exam in the opinion of the Investigator, would compromise subject's safety or data integrity. 2. Employees of the Investigator or research center or their immediate family members. 3. Previous participation in this study. 4. Inability to understand the requirements of the study and the relative information and are unable or not willing to comply with the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Endpoint Post-dose PC20 | Approximately 15 minutes after last inhalation of study product | The primary pharmacodynamic endpoint is the post-dose PC20, which is the provocative concentration of methacholine challenge agent required to reduce the forced expiry volume in one second (FEV1) by 20%, following the administration of different doses of albuterol (or placebo) by inhalation. Primary analysis group -pharmacodynamic population. |
Countries
United States
Participant flow
Recruitment details
Treatments were administered according to a four-treatment, four-period, four-sequence design. 124 eligible subjects were randomized to each one of the four sequences: ABCD Sequence Sequence 1 : A B C D Sequence 2: D C B A Sequence 3: C A D B Sequence 4: B D A C
Participants by arm
| Arm | Count |
|---|---|
| Overall Baseline Summary of Demographic Data and Baseline Characteristics (Safety Population) | 128 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Sequence 1 | Failed Spirometry | 1 |
| Sequence 1 | Restricted medication | 1 |
| Sequence 2 | Adverse Event | 1 |
| Sequence 2 | Failed Spirometry | 1 |
| Sequence 2 | Withdrawal by Subject | 1 |
| Sequence 3 | Failed Spirometry | 1 |
| Sequence 4 | Adverse Event | 1 |
| Sequence 4 | Failed Spirometry | 2 |
Baseline characteristics
| Characteristic | Overall Baseline |
|---|---|
| Age, Continuous | 34.7 years STANDARD_DEVIATION 12.2 |
| FEV1 (Post-saline) | 3.23 Litre STANDARD_DEVIATION 0.74 |
| FEV1 (Pre-saline) | 3.20 Litre STANDARD_DEVIATION 0.72 |
| Number of years patient has suffered from symptoms caused by asthma | 23.62 years STANDARD_DEVIATION 13.17 |
| PC20 FEV1 | 0.95 mg/mL STANDARD_DEVIATION 1.36 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 96 Participants |
| Sex: Female, Male Female | 71 Participants |
| Sex: Female, Male Male | 57 Participants |
| Tobacco Use | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 125 | 0 / 125 | 0 / 123 | 0 / 126 |
| other Total, other adverse events | 7 / 125 | 3 / 125 | 9 / 123 | 5 / 126 |
| serious Total, serious adverse events | 0 / 125 | 0 / 125 | 0 / 123 | 0 / 126 |
Outcome results
Primary
Pharmacodynamic Endpoint Post-dose PC20
The primary pharmacodynamic endpoint is the post-dose PC20, which is the provocative concentration of methacholine challenge agent required to reduce the forced expiry volume in one second (FEV1) by 20%, following the administration of different doses of albuterol (or placebo) by inhalation. Primary analysis group -pharmacodynamic population.
Time frame: Approximately 15 minutes after last inhalation of study product
Population: The statistical analysis was performed based on the Dose-Scale approach. This approach was referenced in FDA's draft Guidance on albuterol sulfate metered/inhalation and described in FDA's draft Guidance on Orlistat capsule. The PC20 data from various treatments (such as placebo, 90 mcg Test, 90 mcg Reference and 180 mcg Reference) from different study period was pooled to perform the Dose-Scale model using NONMEM. Therefore, per test arm values were not reported.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Primary Analysis Group | Pharmacodynamic Endpoint Post-dose PC20 | 114 mg/mL |