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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01189396
First Posted: August 26, 2010
Last Update Posted: July 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Amphastar Pharmaceuticals, Inc.
  Purpose
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 Intervention Phase
Asthma Bronchospasm Chronic Obstructive Pulmonary Disease (COPD) Drug: A006 Drug: Placebo DPI Drug: Proventil-HFA Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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:
  • 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.

  • 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.

  • 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.

  • 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

  • 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

  • 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


Enrollment: 27
Study Start Date: July 2010
Study Completion Date: January 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Information from the National Library of Medicine

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

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.
  Contacts and Locations
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


Locations
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.
Investigators
Study Director: Safety Monitor Amphastar Pharmaceuticals, Inc.
  More Information

Publications:
Responsible Party: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01189396     History of Changes
Other Study ID Numbers: API-A006-CL-C
First Submitted: August 24, 2010
First Posted: August 26, 2010
Last Update Posted: July 2, 2017
Last Verified: June 2017

Keywords provided by Amphastar Pharmaceuticals, Inc.:
asthma
bronchospasm
COPD
reversibility
efficacy

Additional relevant MeSH terms:
Asthma
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Bronchial Spasm
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Albuterol
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