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Albuterol DPI (A006) Clinical Study-B3:Efficacy, Dose-ranging and Safety Evaluation (A006-B3)

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ClinicalTrials.gov Identifier: NCT02210806
Recruitment Status : Completed
First Posted : August 7, 2014
Last Update Posted : April 19, 2017
Sponsor:
Information provided by (Responsible Party):
Amphastar Pharmaceuticals, Inc.

Brief Summary:
This study evaluates the efficacy, dose-ranging and safety profiles of A006, an Albuterol dry powder inhaler (DPI), in the dose range of 110 to 220 mcg per dose in comparison to a DPI Placebo Control and an Albuterol metered dose inhaler (MDI) Active Control.

Condition or disease Intervention/treatment Phase
Asthma Drug: A006 DPI Other: Placebo DPI Drug: Proventil® MDI Phase 2

Detailed Description:
This study is designed to evaluate the efficacy and safety profiles of A006 and to assist in identifying the optimum dose of A006 for future clinical studies. Proventil® HFA MDI, a currently marketed Albuterol MDI product, will be used as an Active Control. The study also employs a Placebo Control DPI, which has the same configuration as the A006 DPI except that it contains no active ingredient.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy, Dose-ranging and Safety Evaluation (A Randomized, Double- or Evaluator-blinded, Active- and Placebo-controlled, Single Dose, Five-arm, Crossover, and Dose-ranging Study of A006 in Adult Asthma Patients)
Study Start Date : July 2014
Actual Primary Completion Date : September 2014
Actual Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Active Comparator: Treatment T1
One inhalation of 110 mcg A006 DPI. Total 110 mcg.
Drug: A006 DPI
Single dose 110 mcg, 1 inhalation
Other Names:
  • Albuterol
  • Albuterol DPI

Active Comparator: Treatment T2
One inhalation of 220 mcg A006 DPI. Total 220 mcg.
Drug: A006 DPI
Single dose 220 mcg, 1 inhalation
Other Names:
  • Albuterol
  • Albuterol DPI

Placebo Comparator: Placebo
One inhalation of placebo DPI . Total 0 mcg
Other: Placebo DPI
Placebo, 1 inhalation
Other Name: Placebo

Active Comparator: Treatment R1
One inhalation of Proventil® MDI Total 90 mcg
Drug: Proventil® MDI
Single dose 90 mcg, 1 inhalation
Other Name: Proventil®

Active Comparator: Treatment R2
Two inhalations of Proventil® MDI, 180 mcg total
Drug: Proventil® MDI
Single dose 90 mcg, 2 inhalations
Other Name: Proventil®




Primary Outcome Measures :
  1. Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 Percentage Change (∆%FEV1) from the Same-Day Pre-Dose Baseline [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Area under the curve (AUC), from baseline to 6 hours post-dose, for the treatment period is calculated using the trapezoidal rule. Statistical analysis is performed using a one-sided t-test.


Secondary Outcome Measures :
  1. Area Under the Curve (AUC[0-6h]) of Placebo Adjusted Post-Dose FEV1 Percentage Change (∆∆%FEV1) from the Same-Day Pre-Dose Baseline [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. ∆∆FEV1% for the study visit is calculated by subtracting the mean ∆%FEV1 for subjects in a randomized treatment arm from their ∆%FEV1. Area under the curve (AUC), from baseline to 6 hours post-dose, for the study visit is calculated using the trapezoidal rule.

  2. Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 Volume Changes (∆FEV1) from the Same-Day Pre-Dose Baseline [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Area under the curve (AUC), from baseline to 6 hours post-dose, for the treatment period is calculated using the trapezoidal rule.

  3. Time to Onset of Bronchodilator Effect (t[onset]) [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. t[onset] is the point where post-dose ∆%FEV1 first reaches ≥ 12% over the pre-dose baseline. Determined by linear interpolation.

  4. Peak Bronchodilator Response (F[max]) [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. F[max] is the maximum post-dose ∆%FEV1.

  5. Time to Peak ∆FEV1 Effect (t[max]) [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. The time to peak ∆FEV1 effect, t[max], is defined as the time of F[max].

  6. Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 in Volume from the Same-Day Pre-Dose Baseline [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Area under the curve (AUC), from baseline to 6 hours post-dose, for the treatment period is calculated using the trapezoidal rule.

  7. F[max] of Post-Dose FEV1 in Volume [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. F[max] of post-dose FEV1 in volume is the maximum post-dose FEV1.

  8. Efficacy Duration-1 [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Efficacy Duration-1 is total duration of bronchodilator effects when ∆%FEV1 is ≥ 12% above the baseline.

  9. Efficacy Duration-2 [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Efficacy Duration-2 is total duration of bronchodilator effects when ∆FEV1 is ≥ 200 mL above the baseline.

  10. Efficacy Duration-3 [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Efficacy Duration-3 is total duration of bronchodilator effects when ∆FEV1 is ≥ 100 mL above the baseline.

  11. Bronchodilator Response [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Subjects that demonstrate a ≥ 12% increase for ∆%FEV1 will be classified as having a bronchodilator response.

  12. Dose Response Curve [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. The dose response curve is the AUC[0-6h] of ∆%FEV1 versus study drug dosage.


Other Outcome Measures:
  1. Systolic and Diastolic Blood Pressure (SBP/DBP) at Screening [ Time Frame: Within 30 minutes prior to reversibility dosing (baseline) and 30 minutes post-reversibility dosing ]
    Subjects have their vital signs, i.e., blood pressure and heart rate, measured prior to reversibility dosing and 30 minutes after dosing during the Screening Visit.

  2. Systolic and Diastolic Blood Pressure (SBP/DBP) [ Time Frame: Within 1 hour prior to dosing (baseline) to 6 hours post-dose ]
    Subjects have their vital signs, i.e., blood pressure and heart rate, measured prior to dosing and at 15 and 30 minutes and 1, 1.5, 2, and 6 hours post-dose during each treatment period.

  3. Heart Rate (HR) at Screening [ Time Frame: Within 30 minutes prior to reversibility dosing (baseline) and 30 minutes post-reversibility dosing ]
    Subjects have their vital signs, i.e., blood pressure and heart rate, measured prior to reversibility dosing and 30 minutes after dosing during the Screening Visit.

  4. Heart Rate (HR) [ Time Frame: Within 1 hour prior to dosing (baseline) to 6 hours post-dose ]
    Subjects have their vital signs, i.e., blood pressure and heart rate, measured prior to dosing and at 15 and 30 minutes and 1, 1.5, 2, and 6 hours post-dose during each treatment period.

  5. 12-Lead ECG QT/QTc Intervals at Screening [ Time Frame: Within 1 hour prior to reversibility dosing ]
    12-Lead ECGs are performed to measure QT and QTc intervals prior to reversibility dosing during the Screening Visit.

  6. 12-Lead ECG QT/QTc Intervals [ Time Frame: Within 1 hour prior to dosing (baseline) to 6 hours post-dose ]
    12-Lead ECGs are performed to measure QT and QTc intervals prior to dosing and at 30 minutes and 1, 2, and 6 hours post-dose during each treatment period.

  7. Number of Subjects with Incidents of Asthma Exacerbation [ Time Frame: Participants will be followed for the duration of the study, an expected average of 3 weeks ]
    An asthma exacerbation incident is defined as significant worsening of clinical symptoms that cannot be adequately relieved by the rescue medication, or significant deterioration of FEV1 tests combined with clinical symptoms. Investigators monitor worsening of asthma symptoms during the treatment period and determine if subjects had experienced an asthma exacerbation.

  8. Number of Subjects that Used Rescue Drug [ Time Frame: Within 30 minutes prior to dosing (baseline) to 6 hours post-dose ]
    Rescue medication may be used to control worsening or exacerbations of asthma symptoms during the study visits when necessary, as determined by the investigator.

  9. Complete Blood Count (CBC) at Screening [ Time Frame: Within 1 hour after reversibility dosing ]
    A CBC is performed as part of the subject safety evaluations with differentials including: red blood cell (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and white blood cell types (WBC).

  10. Complete Blood Count (CBC) at End-of-Study [ Time Frame: 120 minutes post-dose at Visit 5 (within 57 days after Visit 1) ]
    A CBC is performed as part of the subject safety evaluations with differentials including: red blood cell (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and white blood cell types (WBC).

  11. Comprehensive Metabolic Panel (CMP) at Screening [ Time Frame: Within 1 hour after reversibility dosing ]
    A CMP is performed as part of the subject safety evaluations looking at levels for the following: total protein (albumin/globulin), sodium, chloride, potassium, glucose, calcium, carbon dioxide (CO2), blood urea nitrogen (BUN), creatinine, alkaline phosphate (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and bilirubin.

  12. Comprehensive Metabolic Panel (CMP) at End-of-Study [ Time Frame: 120 minutes post-dose at Visit 5 (within 57 days after Visit 1) ]
    A CMP is performed as part of the subject safety evaluations looking at levels for the following: total protein (albumin/globulin), sodium, chloride, potassium, glucose, calcium, carbon dioxide (CO2), blood urea nitrogen (BUN), creatinine, alkaline phosphate (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and bilirubin.

  13. Urinalysis at Screening [ Time Frame: Within 1 hour after reversibility dosing ]
    Routine and microscopic urinalysis is performed as part of the subject safety evaluations to measure urine pH and specific gravity.

  14. Urinalysis at End-of-Study [ Time Frame: 120 minutes post-dose at Visit 5 (within 57 days after Visit 1) ]
    Routine and microscopic urinalysis is performed as part of the subject safety evaluations to measure urine pH and specific gravity.

  15. Incidents of Pregnancy at Screening [ Time Frame: Within 1 hour prior to reversibility dosing ]
    A urinary pregnancy test was performed for women of child-bearing potential as a part of the Screening Visit evaluations to determine the eligibility of the subject for the study.

  16. Incidents of Pregnancy at End-of-Study [ Time Frame: At or after 120 minutes post-dose at Visit 5 (within 57 days after Visit 1) ]
    A urinary pregnancy test was performed for women of child-bearing potential as a part of the End-of-Study safety evaluations to determine if a pregnancy had occurred during the study.

  17. Concomitant Medication Usage [ Time Frame: Participants will be followed for the duration of the study, an expected average of 3 weeks ]
    Concomitant medications used by subjects throughout the duration of the study, from 30 days prior to Screening to End-of-Study evaluations, are recorded by the investigators. The total number of times a specific concomitant medication is used during the study is summarized.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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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:

  • 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 inhaled β-agonist(s) for asthma control
  • Demonstrating a Screening Baseline FEV1 at 50.0 - 85.0% of predicted normal
  • Demonstrating a ≥ 15.0% Airway Reversibility in FEV1 within 30 min after inhaling 2 actuations of Proventil® MDI (180 mcg) at Screening
  • Demonstrating Peak Inspiratory Flow Rate (PIF) within 80-150 L/min (after training), for at least 2 times consecutively with a maximum of 5 attempts
  • Demonstrating proficiency in the use of a DPI and an MDI after training
  • Females of child-bearing potential must be non-pregnant, non-lactating; both males and females enrolled into the study must agree to practice a clinically acceptable form of birth control (including but not limited to, abstinence, double barrier, etc)
  • Having properly consented to participate in the trial

Exclusion Criteria:

  • A smoking history of ≥ 5 pack-years, or having smoked within 6 months prior to Screening
  • Upper respiratory tract infections or lower respiratory tract infection within 6 weeks, prior to Screening
  • Asthma exacerbations that required emergency care or hospitalized treatment, within 4 weeks prior to Screening
  • Any current or recent respiratory conditions that, per investigator discretion, might significantly affect pharmacodynamic response to the study drugs, including cystic fibrosis, bronchiectasis, tuberculosis, emphysema, and other significant respiratory diseases besides asthma
  • Concurrent clinically significant cardiovascular (e.g. hypertension and tachyarrhythmia and bradyarrhythmia), hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignant, or other illnesses that in the opinion of the investigator 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® HFA MDI (i.e., Albuterol, sulfate, lactose, milk protein, HFA-134a, oleic acid, and ethanol)
  • Baseline ECG at Screening or Visit 1 showing any single or multiple premature ventricular contractions (PVC)
  • Baseline ECG at Screening or Visit 1 with a confirmed (through performing a second ECG) QTc reading greater than 450ms
  • 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 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): NCT02210806


Locations
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United States, California
Amphastar Site 0001
San Jose, California, United States, 95117
United States, Oregon
Amphastar Site 0025
Medford, Oregon, United States, 97504
United States, Texas
Amphastar Site 0030
New Braunfels, Texas, United States, 78130
Amphastar Site 0032
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Amphastar Pharmaceuticals, Inc.
Investigators
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Study Director: Safety Monitor Amphastar Pharmeceuticals, Inc.

Publications:
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Responsible Party: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02210806     History of Changes
Other Study ID Numbers: API-A006-CL-B3
First Posted: August 7, 2014    Key Record Dates
Last Update Posted: April 19, 2017
Last Verified: April 2017
Keywords provided by Amphastar Pharmaceuticals, Inc.:
Asthma
Mild-to-moderate persistent asthma
Mild asthma
Moderate asthma
Persistent asthma
Additional relevant MeSH terms:
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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
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