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

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ClinicalTrials.gov Identifier: NCT01189396
Recruitment Status : Completed
First Posted : August 26, 2010
Last Update Posted : July 2, 2017
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Asthma Bronchospasm Chronic Obstructive Pulmonary Disease (COPD) Drug: A006 Drug: Placebo DPI Drug: Proventil-HFA Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double- or Evaluator-blinded, Active- and Placebo-controlled, Cumulative-dose, Dose-escalating, Three-arm, Cross-over Study, in 24 Asthma Patients
Study Start Date : July 2010
Actual Primary Completion Date : December 2010
Actual Study Completion Date : January 2011

Arm Intervention/treatment
Experimental: T
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.
Drug: A006
Albuterol DPI with 180 mcg Albuterol/inhalation

Active Comparator: R
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.
Drug: Proventil-HFA
Albuterol MDI with 90 mcg Albuterol/inhalation

Placebo Comparator: P
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.
Drug: Placebo DPI
Placebo DPI with 0 mcg Albuterol/inhalation

Primary Outcome Measures :
  1. Bronchodilatory efficacy after the escalating and cumulative-doses, up to 1,440 mcg. [ Time Frame: -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 :
  1. AUC0-t of change in FEV1 [ Time Frame: -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.

  2. Time to onset [ Time Frame: 0 - 120 min ]
    Time to onset of bronchodilatory effect, determined by linear interpolation as the point where FEV1 % change first reaches ≥ 12% from FEV10.

  3. Peak Response [ Time Frame: 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.

  4. Adverse Events [ Time Frame: 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

  5. Blood Analysis [ Time Frame: -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

  6. Vital Signs and Electrocardiogram (ECG) [ Time Frame: -15, 5, 35, 65, 100, 155, 275, 455, 815 min post dose 1 ]
    vital signs, including pulse and blood pressure and 12-lead ECG

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01189396

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United States, Oregon
Amphastar Site 0025
Medford, Oregon, United States, 97504
Amphastar Site 0026
Portland, Oregon, United States, 97213
United States, Texas
Amphastar Site 0032
San Antonio, Texas, United States, 78229
United States, Washington
Amphastar Site 0034
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Amphastar Pharmaceuticals, Inc.
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Study Director: Safety Monitor Amphastar Pharmaceuticals, Inc.

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Responsible Party: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01189396    
Other Study ID Numbers: API-A006-CL-C
First Posted: August 26, 2010    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: June 2017
Keywords provided by Amphastar Pharmaceuticals, Inc.:
Additional relevant MeSH terms:
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Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Bronchial Spasm
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action