Albuterol DPI (A006) Clinical Study-B2: Efficacy, Dose-Ranging and Initial Safety Evaluation

Phase 2

Completed

• Conditions: Asthma
• Interventions: Drug: Albuterol DPI 90 mcg/inh; Drug: Albuterol MDI 90 mcg/inh; Drug: Albuterol DPI 25 mcg/inh; Drug: Placebo DPI

• Registration Number: NCT01581177
• Lead Sponsor: Amphastar Pharmaceuticals, Inc.

Brief Summary

The main objective of this study is to evaluate the efficacy, dose-ranging and initial safety profiles of A006, an Albuterol dry powder inhaler (DPI), in the dose range of 25 to 180 mcg per dosing in comparison to a DPI Placebo Control and an Albuterol metered dose inhaler (MDI) Active Control.

This study will be conducted in male and female adult patients who have mild-to-moderate persistent asthma for at least 6 months, but are otherwise generally healthy.

Detailed Description

The main objective of this study is to evaluate the efficacy, dose-ranging and initial safety profiles of A006, an Albuterol dry powder inhaler (DPI), in the dose range of 25 to 180 mcg per dose in comparison to the DPI Placebo Control and the Active (Reference) Control. The study results of this study together with that of A006-B study will be utilized to determine the optimum final dose range of A006 for further clinical studies.

The study will be conducted in male and female adult patients who have mild-to-moderate persistent asthma but are otherwise generally healthy.

Study Timeline

• Study Start: 2012-04
• Study First Submitted: 2012-04-17
• Study First Submitted QC: 2012-04-18
• Study First Posted: 2012-04-20
• Primary Completion: 2012-07
• Study Completion: 2012-08
• Disposition First Submitted: 2017-04-17
• Disposition First Submitted QC: 2017-04-17
• Disposition First Posted: 2017-04-19
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-18
• Last Update Posted: 2017-05-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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 a beta-agonist(s) inhaler
• Demonstrate a Forced Expiratory Volume (FEV1) at 50-85 percent of predicted normal during screening baseline measurement
• Demonstrate an airway reversibility of greater than or equal to 15 percent within 30 minutes of inhaling 2 inhalations of Proventil MDI during screening visit
• Demonstrate Peak Inspiratory Flow Rate (PIF) within 80-150 L/min (after training), at least 2 times consecutively
• Demonstrate ability to use a DPI and MDI inhaler properly after training
• Females must be not pregnant, not lactating, and using a clinically acceptable form of birth control
• Properly agree to participate in the trial

Exclusion Criteria

• A smoking history of more than or equal to 10 years or having smoked within 6 months of screening visit
• Upper respiratory tract infections within 2 weeks or lower respiratory tract infection within 4 weeks prior to screening visit
• Asthma exacerbations that required emergency care or a hospital stay within 4 weeks prior to screening visit
• Any current or recent respiratory tract infections that might affect the response to the study drug as determined by the investigator, including cystic fibrosis, bronchiectasis, tuberculosis, emphysema and other significant respiratory diseases besides asthma
• Current clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignant or other illnesses that could impact the study as determined by the investigator
• Known intolerance or hypersensitivity to any ingredients of the study drug DPI or Proventil MDI (i.e.: Albuterol, sulfate, lactose, milk protein, HFA-134a, oleic acid and ethanol)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
T4	Albuterol DPI 90 mcg/inh	Two inhalations of Albuterol DPI 90 mcg/inh; Total Albuterol dose of 180 mcg
T3	Albuterol DPI 90 mcg/inh	Two inhalations, one of Albuterol DPI 90 mcg/inh and one of Placebo DPI; Total Albuterol dose of 90 mcg
T1	Placebo DPI	Two inhalations, one of Albuterol DPI 25 mcg/inh and one of Placebo DPI; Total Albuterol dose of 25 mcg
R2	Albuterol MDI 90 mcg/inh	Two inhalations of Albuterol MDI 90 mcg/inh; Total Albuterol dose of 180 mcg
T1	Albuterol DPI 25 mcg/inh	Two inhalations, one of Albuterol DPI 25 mcg/inh and one of Placebo DPI; Total Albuterol dose of 25 mcg
T2	Albuterol DPI 25 mcg/inh	Two inhalations of Albuterol DPI 25 mcg/inh; Total Albuterol dose of 50 mcg
R1	Albuterol MDI 90 mcg/inh	One inhalation of Albuterol MDI 90 mcg/inh; Total Albuterol dose of 90 mcg
P	Placebo DPI	Two inhalations Placebo DPI; Total Albuterol dose of 0 mcg
T3	Placebo DPI	Two inhalations, one of Albuterol DPI 90 mcg/inh and one of Placebo DPI; Total Albuterol dose of 90 mcg

Primary Outcome Measures

Name	Time	Method
Change in FEV1 Area Under the Curve (AUC) versus placebo	Visits 1-7, at baseline, 5, 20, 30, 60, 90, 120, 240, 360 minutes post-dose	Serial FEV1 measurements to demonstrate the mean AUC change in percent FEV1 from same-day baseline of A006 versus placebo control

Secondary Outcome Measures

Name	Time	Method
AUC of post-dose FEV1 volume changes from pre-dose baseline to Visit 7	Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose	Determination of FEV1 volume change from pre-dose baseline to post treatment at Visit 7
Placebo AUC of adjusted FEV1 changes	Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose	Determination of change of FEV1 in placebo arm
Duration of effect	Visits 1-7 at 5, 20, 30, 60, 90, 120, 180 and 360 minutes post-dose	Duration of effect, calculated as the total duration of bronchodilator effects when change in FEV1 percent is greater than or equal to 12 percent above baseline.
Time post-dose change in FEV1 percent first reaches greater than or equal to 12 percent over the Pre-dose Baseline	Visits 1-7, at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose	Time to onset of bronchodilator effect (Tonset), determined by linear interpolation as the point where post-dose change in FEV1 percent first reaches greater than or equal to 12 percent over the Pre-dose Baseline.
Peak bronchodilator response (Fmax)	Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose	The peak bronchodilator response (Fmax), defined as the maximum post-dose change in FEV1 percent.
Time to peak FEV1 effect (tmax)	Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose	The time to peak FEV1 effect (tmax), defined as the time of Fmax.
Vital Signs (i.e.: blood pressure and heart rate)	Visits 1-7 and EOS at baseline, 3, 8, 15, 30, 90 and 360 minutes post-dose	Vital signs, i.e. blood pressure (SBP/DBP) and heart rate (HR), at pre-dose baseline, and 3, 8, 15, 30, 90, and 360 min post-dose.
Serum potassium	Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose	Determination of serum potassium levels, at pre-dose baseline, and at 15, 35 and 120 min post-dose.
Asthma exacerbation incidents	Visits 1-7 and EOS	Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study.
Asthma management/ rescue drug usage	Visits 1-7 and EOS	Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study.
CBC	Screening and End-of-Study Visit	Evaluation of CBC in all subjects at screening and end-of-study visit.
Bronchodilatory Response Rate (R percent)	Visits 1-7 at 60 minutes	Evaluation of Bronchodilatory Response Rate (R percent) of responders who demonstrate a greater than or equal to 12 percent increase for change in FEV1 percent during the initial 60 min post-dose.
Dose response curve: AUC of change in percent FEV1 versus Dose	Visits 1-7	Evaluation of change in FEV1 in relation to dose.
12-lead ECG (for routine and QT/QTc)	Visits 1-7 at baseline, 10, 50 and 360 minutes post-dose	Measurement of 12-lead ECG (for routine and QT/QTc), at pre-dose baseline, and at 10, 50, and 360 min post-dose.
Serum glucose	Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose	Determination of Serum glucose, at pre-dose baseline, and at 15, 35 and 120 min post-dose.
Physical examination	Screening and End-of-Study Visit	Physical examination of all subjects performed at screening and end-of-study visit to evaluate subject's general health.
Comprehensive metabolic panel	Screening and End-of-Study Visit	Comprehensive metabolic panel performed on all subjects at screening and end-of-study visit.
Urinalysis	Screening and End-of-Study Visit	Urinalysis performed on all subjects at screening and end-of-study visit.
Pregnancy test	Screening and End-of-Study Visit	A pregnancy test for women of child bearing potential at screening and end-of-study visit.
Medication interactions	Screening, Visits 1-7 and End-of-Study Visit	Evaluation of concomitant medications used by subjects throughout the study and their potential to affect the study
Number of participants with adverse events as a measure of safety and tolerability	Screening, Visits 1-7, End-of-Study Visit	Adverse drug events whether observed by investigators or reported by subjects, will be documented, evaluated, followed up, and treated if deemed necessary.

Trial Locations

Locations (4)

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

Amphastar Site 0001; 🇺🇸 San Jose, California, United States

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

Amphastar Site 0030; 🇺🇸 New Braunfels, Texas, United States