Clinical trial NCT02210806: Albuterol DPI (A006) Clinical Study-B3:Efficacy, Dose-ranging and Safety Evaluation
Official title: Efficacy, Dose-ranging and Safety Evaluation (A Randomized, Double- or Evaluator-blinded, Active- and Placebo-controlled, Single Dose, Five-arm, Crossover, and Dose-ranging Study of A006 in Adult Asthma Patients)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
Mild-to-moderate persistent asthma
Mild asthma
Moderate asthma
Persistent asthma
Lead sponsor: Amphastar Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-08-07
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 Percentage Change (∆%FEV1) from the Same-Day Pre-Dose Baseline
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
Secondary outcomes:
measure: Area Under the Curve (AUC[0-6h]) of Placebo Adjusted Post-Dose FEV1 Percentage Change (∆∆%FEV1) from the Same-Day Pre-Dose Baseline
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
measure: Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 Volume Changes (∆FEV1) from the Same-Day Pre-Dose Baseline
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
measure: Time to Onset of Bronchodilator Effect (t[onset])
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
measure: Peak Bronchodilator Response (F[max])
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
measure: Time to Peak ∆FEV1 Effect (t[max])
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
measure: Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 in Volume from the Same-Day Pre-Dose Baseline
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
measure: F[max] of Post-Dose FEV1 in Volume
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
measure: Efficacy Duration-1
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
measure: Efficacy Duration-2
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
measure: Efficacy Duration-3
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
measure: Bronchodilator Response
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
measure: Dose Response Curve
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
Other outcomes:
measure: Systolic and Diastolic Blood Pressure (SBP/DBP) at Screening
timeFrame: Within 30 minutes prior to reversibility dosing (baseline) and 30 minutes post-reversibility dosing
measure: Systolic and Diastolic Blood Pressure (SBP/DBP)
timeFrame: Within 1 hour prior to dosing (baseline) to 6 hours post-dose
measure: Heart Rate (HR) at Screening
timeFrame: Within 30 minutes prior to reversibility dosing (baseline) and 30 minutes post-reversibility dosing
measure: Heart Rate (HR)
timeFrame: Within 1 hour prior to dosing (baseline) to 6 hours post-dose
measure: 12-Lead ECG QT/QTc Intervals at Screening
timeFrame: Within 1 hour prior to reversibility dosing
measure: 12-Lead ECG QT/QTc Intervals
timeFrame: Within 1 hour prior to dosing (baseline) to 6 hours post-dose
measure: Number of Subjects with Incidents of Asthma Exacerbation
timeFrame: Participants will be followed for the duration of the study, an expected average of 3 weeks
measure: Number of Subjects that Used Rescue Drug
timeFrame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose
measure: Complete Blood Count (CBC) at Screening
timeFrame: Within 1 hour after reversibility dosing
measure: Complete Blood Count (CBC) at End-of-Study
timeFrame: 120 minutes post-dose at Visit 5 (within 57 days after Visit 1)
measure: Comprehensive Metabolic Panel (CMP) at Screening
timeFrame: Within 1 hour after reversibility dosing
measure: Comprehensive Metabolic Panel (CMP) at End-of-Study
timeFrame: 120 minutes post-dose at Visit 5 (within 57 days after Visit 1)
measure: Urinalysis at Screening
timeFrame: Within 1 hour after reversibility dosing
measure: Urinalysis at End-of-Study
timeFrame: 120 minutes post-dose at Visit 5 (within 57 days after Visit 1)
measure: Incidents of Pregnancy at Screening
timeFrame: Within 1 hour prior to reversibility dosing
measure: Incidents of Pregnancy at End-of-Study
timeFrame: At or after 120 minutes post-dose at Visit 5 (within 57 days after Visit 1)
measure: Concomitant Medication Usage
timeFrame: Participants will be followed for the duration of the study, an expected average of 3 weeks
Locations:
city: San Jose
country: United States
facility: Amphastar Site 0001
state: California
city: Medford
country: United States
facility: Amphastar Site 0025
state: Oregon
city: New Braunfels
country: United States
facility: Amphastar Site 0030
state: Texas
city: San Antonio
country: United States
facility: Amphastar Site 0032
state: Texas
Study officials:
affiliation: Amphastar Pharmeceuticals, Inc.
name: Safety Monitor
role: STUDY_DIRECTOR
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