Albuterol DPI (A006) Clinical Study-B3:Efficacy, Dose-ranging and Safety Evaluation
- Registration Number
- NCT02210806
- Lead Sponsor
- Amphastar Pharmaceuticals, Inc.
- Brief Summary
This study evaluates the efficacy, dose-ranging and safety profiles of A006, an Albuterol dry powder inhaler (DPI), in the dose range of 110 to 220 mcg per dose in comparison to a DPI Placebo Control and an Albuterol metered dose inhaler (MDI) Active Control.
- Detailed Description
This study is designed to evaluate the efficacy and safety profiles of A006 and to assist in identifying the optimum dose of A006 for future clinical studies. Proventil® HFA MDI, a currently marketed Albuterol MDI product, will be used as an Active Control. The study also employs a Placebo Control DPI, which has the same configuration as the A006 DPI except that it contains no active ingredient.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 22
- Generally healthy, male and female adults, 18-55 years of age at Screening
- With mild-to-moderate persistent asthma for at least 6 months prior to Screening, and having used inhaled β-agonist(s) for asthma control
- Demonstrating a Screening Baseline FEV1 at 50.0 - 85.0% of predicted normal
- Demonstrating a ≥ 15.0% Airway Reversibility in FEV1 within 30 min after inhaling 2 actuations of Proventil® MDI (180 mcg) at Screening
- Demonstrating Peak Inspiratory Flow Rate (PIF) within 80-150 L/min (after training), for at least 2 times consecutively with a maximum of 5 attempts
- Demonstrating proficiency in the use of a DPI and an MDI after training
- Females of child-bearing potential must be non-pregnant, non-lactating; both males and females enrolled into the study must agree to practice a clinically acceptable form of birth control (including but not limited to, abstinence, double barrier, etc)
- Having properly consented to participate in the trial
- A smoking history of ≥ 5 pack-years, or having smoked within 6 months prior to Screening
- Upper respiratory tract infections or lower respiratory tract infection within 6 weeks, prior to Screening
- Asthma exacerbations that required emergency care or hospitalized treatment, within 4 weeks prior to Screening
- Any current or recent respiratory conditions that, per investigator discretion, might significantly affect pharmacodynamic response to the study drugs, including cystic fibrosis, bronchiectasis, tuberculosis, emphysema, and other significant respiratory diseases besides asthma
- Concurrent clinically significant cardiovascular (e.g. hypertension and tachyarrhythmia and bradyarrhythmia), hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignant, or other illnesses that in the opinion of the investigator could impact on the conduct, safety and evaluation of the study
- Known intolerance or hypersensitivity to any of the ingredients of the study drug DPI or Proventil® HFA MDI (i.e., Albuterol, sulfate, lactose, milk protein, HFA-134a, oleic acid, and ethanol)
- Baseline ECG at Screening or Visit 1 showing any single or multiple premature ventricular contractions (PVC)
- Baseline ECG at Screening or Visit 1 with a confirmed (through performing a second ECG) QTc reading greater than 450ms
- Use of prohibited drugs or failure to observe the drug washout restrictions
- Having been on other clinical drug/device studies in the last 30 days prior to Screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment R1 Proventil® MDI One inhalation of Proventil® MDI Total 90 mcg Treatment R2 Proventil® MDI Two inhalations of Proventil® MDI, 180 mcg total Placebo Placebo DPI One inhalation of placebo DPI . Total 0 mcg Treatment T1 A006 DPI One inhalation of 110 mcg A006 DPI. Total 110 mcg. Treatment T2 A006 DPI One inhalation of 220 mcg A006 DPI. Total 220 mcg.
- Primary Outcome Measures
Name Time Method Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 Percentage Change (∆%FEV1) from the Same-Day Pre-Dose Baseline Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Area under the curve (AUC), from baseline to 6 hours post-dose, for the treatment period is calculated using the trapezoidal rule. Statistical analysis is performed using a one-sided t-test.
- Secondary Outcome Measures
Name Time Method Time to Onset of Bronchodilator Effect (t[onset]) Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. t\[onset\] is the point where post-dose ∆%FEV1 first reaches ≥ 12% over the pre-dose baseline. Determined by linear interpolation.
Area Under the Curve (AUC[0-6h]) of Placebo Adjusted Post-Dose FEV1 Percentage Change (∆∆%FEV1) from the Same-Day Pre-Dose Baseline Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. ∆∆FEV1% for the study visit is calculated by subtracting the mean ∆%FEV1 for subjects in a randomized treatment arm from their ∆%FEV1. Area under the curve (AUC), from baseline to 6 hours post-dose, for the study visit is calculated using the trapezoidal rule.
Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 Volume Changes (∆FEV1) from the Same-Day Pre-Dose Baseline Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Area under the curve (AUC), from baseline to 6 hours post-dose, for the treatment period is calculated using the trapezoidal rule.
Peak Bronchodilator Response (F[max]) Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. F\[max\] is the maximum post-dose ∆%FEV1.
Time to Peak ∆FEV1 Effect (t[max]) Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. The time to peak ∆FEV1 effect, t\[max\], is defined as the time of F\[max\].
F[max] of Post-Dose FEV1 in Volume Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. F\[max\] of post-dose FEV1 in volume is the maximum post-dose FEV1.
Efficacy Duration-1 Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Efficacy Duration-1 is total duration of bronchodilator effects when ∆%FEV1 is ≥ 12% above the baseline.
Efficacy Duration-2 Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Efficacy Duration-2 is total duration of bronchodilator effects when ∆FEV1 is ≥ 200 mL above the baseline.
Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 in Volume from the Same-Day Pre-Dose Baseline Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Area under the curve (AUC), from baseline to 6 hours post-dose, for the treatment period is calculated using the trapezoidal rule.
Efficacy Duration-3 Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Efficacy Duration-3 is total duration of bronchodilator effects when ∆FEV1 is ≥ 100 mL above the baseline.
Bronchodilator Response Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Subjects that demonstrate a ≥ 12% increase for ∆%FEV1 will be classified as having a bronchodilator response.
Dose Response Curve Within 30 minutes prior to dosing (baseline) to 6 hours post-dose The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. The dose response curve is the AUC\[0-6h\] of ∆%FEV1 versus study drug dosage.
Trial Locations
- Locations (4)
Amphastar Site 0030
🇺🇸New Braunfels, Texas, United States
Amphastar Site 0025
🇺🇸Medford, Oregon, United States
Amphastar Site 0001
🇺🇸San Jose, California, United States
Amphastar Site 0032
🇺🇸San Antonio, Texas, United States