Escalating and Cumulative-Dose Study of Pharmacokinetics (PK), Pharmacodynamics (PD) and Safety of A006

Phase 2

Completed

• Conditions: Asthma; Bronchospasm; Chronic Obstructive Pulmonary Disease (COPD)
• Interventions: Drug: A006; Drug: Proventil-HFA; Drug: Placebo DPI

• Registration Number: NCT01189396
• Lead Sponsor: Amphastar Pharmaceuticals, Inc.

Brief Summary

The main objective is to evaluate the bronchodilatory efficacy, safety and pharmacokinetic profiles of A006 (Albuterol Dry Powder Inhaler (DPI)), in comparison with those of an active control, Proventil-HFA (Albuterol Metered Dose Inhaler (MDI)), and a Placebo DPI in escalating and cumulative-doses up to 1440 mcg, eight (8) times of the proposed clinical dose.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2010-08-24
• Study First Submitted QC: 2010-08-25
• Study First Posted: 2010-08-26
• Primary Completion: 2010-12
• Study Completion: 2011-01
• Disposition First Submitted: 2017-04-17
• Disposition First Submitted QC: 2017-05-18
• Disposition First Posted: 2017-05-19
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-27
• Last Update Posted: 2017-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

• Body weight ≥ 50 kg for men and ≥ 45 kg for women, and BMI within the range of 18.5 - 30.0 kg/m2 inclusive;
• Sitting blood pressure ≤ 135/90 mmHg;
• Demonstrating negative alcohol/drug screen tests;
• Demonstrating negative HIV, HBsAg and HCV-Ab screen tests;
• 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 Mean Screening Baseline FEV1 at 50.0 - 85.0 % of predicted normal;
• Demonstrating a ≥ 15.0% Airway Reversibility in FEV1 within 30(±5) min after inhaling 2 actuations of Proventil-HFA;
• Demonstrating Peak Inspiratory Flow Rate within 80-150 L/min;
• Demonstrating proficiency in the use of DPI and MDI after training;
• Females of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control;
• Having properly consented to participate in the trial.

Exclusion Criteria

• Smoking history of ≥ 10 pack-years, or having smoked within 6 months prior to Screening;
• Upper respiratory tract infections within 2 wk, or lower respiratory tract infection within 4 wk;
• Asthma exacerbations that required emergency care or hospitalized treatment, within 4 wk prior;
• Any current or recent respiratory conditions that might significantly affect pharmacodynamic response to the study drugs, besides asthma;
• Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignancies, or other illnesses that could impact on the conduct, safety and evaluation of the study;
• Known intolerance or hypersensitivity to any of the ingredients of the A006 or Proventil-HFA;
• 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;
• Having donated blood within the last 30 days prior to Screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
T	A006	Four doses of A006 taken in 30 minute intervals. Doses will have an escalating number of inhalations (1, 1, 2, and 4 inhalations). Total cumulative Albuterol dose at 90 minutes is 1440 mcg.
R	Proventil-HFA	Four doses of Proventil-HFA taken in 30 minute intervals. Doses will have an escalating number of inhalations (2, 2, 4, and 8 inhalations). Total cumulative Albuterol dose at 90 minutes is 1440 mcg.
P	Placebo DPI	Four doses of Placebo DPI taken in 30 minute intervals. Doses will have an escalating number of inhalations (1, 1, 2, and 4 inhalations). Total cumulative Albuterol dose at 90 minutes is 0 mcg.

Primary Outcome Measures

Name	Time	Method
Bronchodilatory efficacy after the escalating and cumulative-doses, up to 1,440 mcg.	-15 min predose, 15 min post dose 1, 2 and 3 and 15, 45, 90, 120, 180, 240, 360 min post dose 4	Area Under the Curve (AUC)0-t of percent change in Forced Expiratory Volume in 1 second (FEV1), which is defined as the area under curve of post-dose FEV1 percentage changes from the Pre-dose Baseline FEV1 (FEV10) versus time. Doses are at 0, 30, 60 and 90 min.

Secondary Outcome Measures

Name	Time	Method
AUC0-t of change in FEV1	-15, 15 min post 1, 2, and 3, and 15, 90, 120, 240, and 360min post dose 4	AUC of FEV1 volume post-dose changes (change in Volume) from the Pre-dose Baseline FEV1 (FEV10). Doses are at 0, 30, 60 and 90 min.
Time to onset	0 - 120 min	Time to onset of bronchodilatory effect, determined by linear interpolation as the point where FEV1 % change first reaches ≥ 12% from FEV10.
Peak Response	15 min post dose 1, 2 and 3 and 15, 45, 90, 120, 180, 240, and 360 min post dose 4	The peak bronchodilator response, defined as the maximum post-dose FEV1 % change. Doses are at time 0, 30, 60, and 90 min.
Adverse Events	Time 0, 15, 45, 75, 105, 150, 195, 130, 190, 250, 435 minutes post dose 1	The adverse drug events (ADE) that are observed with Proventil-HFA may be expected with the use of A006
Vital Signs and Electrocardiogram (ECG)	-15, 5, 35, 65, 100, 155, 275, 455, 815 min post dose 1	vital signs, including pulse and blood pressure and 12-lead ECG
Blood Analysis	-15, 10, 25,40, 55, 70, 85, 95, 115, 145, 175, 210, 270, 330, 690 min post dose 1	serum glucose and potassium analysis and PK analysis

Trial Locations

Locations (4)

Amphastar Site 0026; 🇺🇸 Portland, Oregon, United States

Amphastar Site 0025; 🇺🇸 Medford, Oregon, United States

Amphastar Site 0032; 🇺🇸 San Antonio, Texas, United States

Amphastar Site 0034; 🇺🇸 Seattle, Washington, United States