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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01581177
First received: April 17, 2012
Last updated: July 9, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Albuterol 25 mcg, Placebo
Drug: Albuterol 0.25 mcg
Drug: Albuterol 90 mcg, Placebo
Drug: Albuterol, 90 mcg
Drug: Placebo
Drug: Proventil 90 mcg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double- or Evaluator-blind, Active- and Placebo-controlled, Single Dose, Seven-arm, Crossover Dose-ranging Study of A006 in Adult Asthma Patients

Resource links provided by NLM:


Further study details as provided by Amphastar Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Change in FEV1 Area Under the Curve (AUC) versus placebo [ Time Frame: Visits 1-7, at baseline, 5, 20, 30, 60, 90, 120, 240, 360 minutes post-dose ] [ Designated as safety issue: No ]
    Serial FEV1 measurements to demonstrate the mean AUC change in percent FEV1 from same-day baseline of A006 versus placebo control


Secondary Outcome Measures:
  • Placebo AUC of adjusted FEV1 changes [ Time Frame: Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose ] [ Designated as safety issue: No ]
    Determination of change of FEV1 in placebo arm

  • AUC of post-dose FEV1 volume changes from pre-dose baseline to Visit 7 [ Time Frame: Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose ] [ Designated as safety issue: No ]
    Determination of FEV1 volume change from pre-dose baseline to post treatment at Visit 7

  • Time post-dose change in FEV1 percent first reaches greater than or equal to 12 percent over the Pre-dose Baseline [ Time Frame: Visits 1-7, at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose ] [ Designated as safety issue: No ]
    The peak bronchodilator response (Fmax), defined as the maximum post-dose change in FEV1 percent.

  • Time to peak FEV1 effect (tmax) [ Time Frame: Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose ] [ Designated as safety issue: No ]
    The time to peak FEV1 effect (tmax), defined as the time of Fmax.

  • Duration of effect [ Time Frame: Visits 1-7 at 5, 20, 30, 60, 90, 120, 180 and 360 minutes post-dose ] [ Designated as safety issue: No ]
    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.

  • Bronchodilatory Response Rate (R percent) [ Time Frame: Visits 1-7 at 60 minutes ] [ Designated as safety issue: No ]
    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 [ Time Frame: Visits 1-7 ] [ Designated as safety issue: No ]
    Evaluation of change in FEV1 in relation to dose.

  • Vital Signs (i.e.: blood pressure and heart rate) [ Time Frame: Visits 1-7 and EOS at baseline, 3, 8, 15, 30, 90 and 360 minutes post-dose ] [ Designated as safety issue: Yes ]
    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.

  • 12-lead ECG (for routine and QT/QTc) [ Time Frame: Visits 1-7 at baseline, 10, 50 and 360 minutes post-dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose ] [ Designated as safety issue: Yes ]
    Determination of Serum glucose, at pre-dose baseline, and at 15, 35 and 120 min post-dose.

  • Serum potassium [ Time Frame: Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose ] [ Designated as safety issue: Yes ]
    Determination of serum potassium levels, at pre-dose baseline, and at 15, 35 and 120 min post-dose.

  • Asthma exacerbation incidents [ Time Frame: Visits 1-7 and EOS ] [ Designated as safety issue: Yes ]
    Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study.

  • Asthma management/ rescue drug usage [ Time Frame: Visits 1-7 and EOS ] [ Designated as safety issue: Yes ]
    Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study.

  • Physical examination [ Time Frame: Screening and End-of-Study Visit ] [ Designated as safety issue: Yes ]
    Physical examination of all subjects performed at screening and end-of-study visit to evaluate subject's general health.

  • CBC [ Time Frame: Screening and End-of-Study Visit ] [ Designated as safety issue: Yes ]
    Evaluation of CBC in all subjects at screening and end-of-study visit.

  • Comprehensive metabolic panel [ Time Frame: Screening and End-of-Study Visit ] [ Designated as safety issue: Yes ]
    Comprehensive metabolic panel performed on all subjects at screening and end-of-study visit.

  • Urinalysis [ Time Frame: Screening and End-of-Study Visit ] [ Designated as safety issue: Yes ]
    Urinalysis performed on all subjects at screening and end-of-study visit.

  • Pregnancy test [ Time Frame: Screening and End-of-Study Visit ] [ Designated as safety issue: Yes ]
    A pregnancy test for women of child bearing potential at screening and end-of-study visit.

  • Medication interactions [ Time Frame: Screening, Visits 1-7 and End-of-Study Visit ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Screening, Visits 1-7, End-of-Study Visit ] [ Designated as safety issue: Yes ]
    Adverse drug events whether observed by investigators or reported by subjects, will be documented, evaluated, followed up, and treated if deemed necessary.


Enrollment: 28
Study Start Date: April 2012
Study Completion Date: August 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Albuterol (25 mcg)/Placebo
Arm T1 is a double-blinded, experimental treatment arm consisting of 25 mcg of A006 during first inhalation and a placebo during second inhalation (a total of 25 mcg of Albuterol per dose)
Drug: Albuterol 25 mcg, Placebo
Albuterol Dry Powder, 25 mcg per inhalation, 1 inhalation followed by 1 inhalation of placebo
Experimental: Albuterol (50 mcg)
Arm T2 is a double-blinded, experimental treatment arm consisting of 25 mcg of A006 during first inhalation and 25 mcg of A006 during second inhalation (a total of 50 mcg of Albuterol per dose).
Drug: Albuterol 0.25 mcg
Albuterol Dry Powder Inhalation 0.25 mcg, 2 inhalations
Experimental: Albuterol (90 mcg)/Placebo
Arm T3 is a double-blinded, experimental treatment arm consisting of 90 mcg of A006 during first inhalation and a placebo during second inhalation (a total of 90 mcg of Albuterol per dose).
Drug: Albuterol 90 mcg, Placebo
Albuterol Dry Powder, 90 mcg per inhalation, 1 inhalation, followed by 1 inhalation of placebo
Experimental: Albuterol (180 mcg)
Arm T4 is a double-blinded, experimental treatment arm consisting of 90 mcg of A006 during first inhalation and 90 mcg of A006 during second inhalation (a total of 180 mcg of Albuterol per dose).
Drug: Albuterol, 90 mcg
Albuterol Dry Powder, 90 mcg per inhalation, 2 inhalations
Placebo Comparator: Placebo
Arm P is a double-blinded placebo treatment arm consisting of placebo during both inhalations.
Drug: Placebo
Two inhalations of placebo
Active Comparator: Proventil (90 mcg)
Arm R1 is an evaluator blinded comparator treatment arm consisting of one inhalation of 90 mcg of Proventil (a total of 90 mcg of Proventil per dose).
Drug: Proventil 90 mcg
Proventil, 90 mcg per inhalation, 1 inhalation
Active Comparator: Proventil (180 mcg)
Arm R2 is an evaluator blinded, comparator arm consisting of 90 mcg of Proventil during first inhalation and 90 mcg of Proventil during second inhalation (a total of 180 mcg of Proventil per dose).
Drug: Proventil 90 mcg
Proventil, 90 mcg per inhalation, 2 inhalations

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01581177

Locations
United States, California
Amphastar Site 1
San Jose, California, United States, 95117
United States, Oregon
Amphastar Site 2
Medford, Oregon, United States, 97504
United States, Texas
Amphastar Site 3
New Braunfels, Texas, United States, 78130
Amphastar Site 4
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Amphastar Pharmaceuticals, Inc.
Investigators
Study Chair: John Gao, M.D. Amphastar Pharmaceuticals, Inc.
  More Information

Publications:
Responsible Party: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01581177     History of Changes
Other Study ID Numbers: API-A006-CL-B2
Study First Received: April 17, 2012
Last Updated: July 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Amphastar Pharmaceuticals, Inc.:
asthma
mild-to-moderate persistent asthma
mild asthma
moderate asthma
persistent asthma

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Albuterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 16, 2014