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

This study has been completed.
Sponsor:
Information provided by:
Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01189396
First received: August 24, 2010
Last updated: January 23, 2012
Last verified: January 2012

August 24, 2010
January 23, 2012
July 2010
December 2010   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01189396 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    The adverse drug events (ADE) that are observed with Albuterol MDI may be expected with the use of Albuterol DPI
  • Blood Analysis [ Time Frame: -15, 10, 25,40, 55, 70, 85, 95, 115, 145, 175, 210, 270, 330, 690 min post dose 1 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    vital signs, including pulse and blood pressure and 12-lead ECG
Same as current
Not Provided
Not Provided
 
Escalating and Cumulative-Dose Study of Pharmacokinetics (PK), Pharmacodynamics (PD) and Safety of A006
A Randomized, Double- or Evaluator-blinded, Active- and Placebo-controlled, Cumulative-dose, Dose-escalating, Three-arm, Cross-over Study, in 24 Asthma Patients

The main objective is to evaluate the bronchodilatory efficacy, safety and pharmacokinetic profiles of A006, in comparison with those of an active control, Proventil®-HFA MDI, and a placebo control DPI, in escalating and cumulative-doses up to 1,440 mcg, eight (8) times of the proposed clinical dose.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Asthma
  • Bronchospasm
  • Chronic Obstructive Pulmonary Disease (COPD)
  • Drug: Albuterol Inhalation Powder
    Albuterol dry powder inhaler, 180 mcg/inhalation, escalating dose 180 mcg, 180 mcg, 360 mcg, 720 mcg, at 30 min intervals, total cumulative dose 1440
    Other Name: A006
  • Drug: Placebo Control
    Placebo control contains only lactose in amounts identical to the lactose contained in A006. 1, 1, 2, and 4 inhalation at 30 min intervals.
  • Drug: Active Comparator
    Proventil HFA albuterol inhalation aerosol, 90 mcg/inhalation, 2, 2, 4, and 8 inhalations per dose a 30 min intervals, total accumulated dose 1440 mcg.
    Other Name: albuterol inhalation aerosol HFA
  • Experimental: Treatment 1
    Albuterol Inhalation Powder escalating dose up to 180 mcg/dose, cumulative dose up to 1440 mcg, dosing at 30 min. intervals
    Intervention: Drug: Albuterol Inhalation Powder
  • Active Comparator: Active Control
    Proventil HFA albuterol inhalation aerosol, 90 mcg/ inhalation
    Intervention: Drug: Active Comparator
  • Placebo Comparator: Placebo Control
    Placebo control, 0 mcg albuterol/dose, contains only lactose as carrier.
    Intervention: Drug: Placebo Control

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
27
January 2011
December 2010   (final data collection date for primary outcome measure)

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® MDI;
  • 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 study drug DPI or Proventil® MDI;
  • 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.
Both
18 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01189396
API-A006-CL-C
No
Medical Director, Amphastar Pharmaceuticals, Inc.
Amphastar Pharmaceuticals, Inc.
Not Provided
Study Director: Medical Director, M.D., Ph.D. Amphastar Pharmaceuticals, Inc.
Amphastar Pharmaceuticals, Inc.
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP