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Evaluation of Pharmacokinetics and Safety of A006 in Healthy Volunteers (A006-D)

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ClinicalTrials.gov Identifier: NCT02271334
Recruitment Status : Completed
First Posted : October 22, 2014
Last Update Posted : April 19, 2017
Sponsor:
Information provided by (Responsible Party):
Amphastar Pharmaceuticals, Inc.

Brief Summary:
The objective of this study is to evaluate the pharmacokinetics (PK) and safety profiles of A006, an Albuterol dry powder inhaler (DPI), following a single dose of 110 mcg (T1) or 220 mcg (T2), in healthy male and female adult volunteers.

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

Detailed Description:

This study is a randomized, double or evaluator-blinded, single dose, four-arm, crossover PK study in eighteen (18) healthy volunteers, both male and female adults, at 18-40 years of age.

All candidates will be screened and only those who satisfy all enrollment criteria will be enrolled into this study. Each study subject will participate in a screening visit and four (4) study visits with one (1) randomized study treatment given in each visit.

PK samples will be analyzed with an established LC/MS/MS method. An End-of-Study (EOS) safety evaluation will be conducted at the end of Study Visit-4.


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: Evaluation of Pharmacokinetics and Safety of A006 in Healthy Volunteers (A Randomized, Double- or Evaluator-blinded, Single-dose, Four-arm, Crossover Pharmacokinetics (PK) Study in Healthy Adults)
Study Start Date : August 2014
Actual Primary Completion Date : October 2014
Actual Study Completion Date : March 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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

Experimental: 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

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

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




Primary Outcome Measures :
  1. Area Under the Curve of Drug Concentration versus Time (AUC[0-t]) [ Time Frame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose ]
    Subject PK blood samples will be taken prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. PK samples will be analyzed using a validated test method. Area under the curve of the drug concentration versus time curve (AUC[0-t]) for each treatment period will be calculated using the trapezoidal rule.

  2. Peak Plasma Concentration (C[max]) [ Time Frame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose ]
    Subject PK blood samples will be taken prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. PK samples will be analyzed using a validated test method. Peak plasma concentration (C[max]) will be the highest concentration of Albuterol during each treatment period.

  3. Time to Reach Peak Plasma Concentration (t[max]) [ Time Frame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose ]
    Subject PK blood samples will be taken prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. PK samples will be analyzed using a validated test method. Time to reach peak plasma concentration (t[max]) will be the time it takes to reach the highest concentration of Albuterol during each treatment period.

  4. Plasma Albuterol Concentrations at All Time Points [ Time Frame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose ]
    Subject PK blood samples will be taken prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. PK samples will be analyzed using a validated test method. Plasma Albuterol concentrations at these time points will be reported during each treatment period.


Other Outcome Measures:
  1. Systolic Blood Pressure (SBP) at Screening [ Time Frame: Within 14 days prior to Day 1 (Visit 1) ]
    Subjects will have their vital signs, i.e., blood pressure and heart rate, measured during the Screening Visit to ensure they are generally healthy.

  2. Systolic Blood Pressure (SBP) [ Time Frame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose ]
    Subject will have their vital signs, i.e., blood pressure and heart rate, measured prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period.

  3. Diastolic Blood Pressure (DBP) at Screening [ Time Frame: Within 14 days prior to Day 1 (Visit 1) ]
    Subjects will have their vital signs, i.e., blood pressure and heart rate, measured during the Screening Visit to ensure they are generally healthy.

  4. Diastolic Blood Pressure (DBP) [ Time Frame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose ]
    Subject will have their vital signs, i.e., blood pressure and heart rate, measured prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period.

  5. Heart Rate (HR) at Screening [ Time Frame: Within 14 days prior to Day 1 (Visit 1) ]
    Subjects will have their vital signs, i.e., blood pressure and heart rate, measured during the Screening Visit to ensure they are generally healthy.

  6. Heart Rate (HR) [ Time Frame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose ]
    Subject will have their vital signs, i.e., blood pressure and heart rate, measured prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period.

  7. 12-Lead ECG QT Intervals at Screening [ Time Frame: Within 14 days prior to Day 1 (Visit 1) ]
    12-Lead ECGs will be performed to measure QT and QTc intervals during the Screening Visit to ensure absence of overt cardiac illnesses.

  8. 12-Lead ECG QT Intervals [ Time Frame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose ]
    12-Lead ECGs will be performed to measure QT and QTc intervals prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period.

  9. 12-Lead ECG QTc Intervals at Screening [ Time Frame: Within 14 days prior to Day 1 (Visit 1) ]
    12-Lead ECGs will be performed to measure QT and QTc intervals during the Screening Visit to ensure absence of overt cardiac illnesses.

  10. 12-Lead ECG QTc Intervals [ Time Frame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose ]
    12-Lead ECGs will be performed to measure QT and QTc intervals prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period.

  11. Complete Blood Count (CBC) at Screening [ Time Frame: Within 14 days prior to Day 1 (Visit 1) ]
    A CBC will be performed as part of the subject safety evaluations at screening.

  12. Complete Blood Count (CBC) at End-of-Study [ Time Frame: 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1)) ]
    A CBC will be performed as part of the End-of-Study subject safety evaluations at end-of-study.

  13. Comprehensive Metabolic Panel (CMP) at Screening [ Time Frame: Within 14 days prior to Day 1 (Visit 1) ]
    A CMP will be performed as part of the subject safety evaluations at screening.

  14. Comprehensive Metabolic Panel (CMP) at End-of-Study [ Time Frame: 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1)) ]
    A CMP will be performed as part of the End-of-Study subject safety evaluations at end-of-study.

  15. Urinalysis at Screening [ Time Frame: Within 14 days prior to Day 1 (Visit 1) ]
    Routine and microscopic urinalysis will be performed as part of the subject safety evaluations at screening.

  16. Urinalysis at End-of-Study [ Time Frame: 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1)) ]
    Routine and microscopic urinalysis will be performed as part of the End-of-Study subject safety evaluations at end-of-study.

  17. Incidents of Pregnancy at Screening [ Time Frame: Within 14 days prior to Day 1 (Visit 1) ]
    A urinary pregnancy test will be 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.

  18. Incidents of Pregnancy at End-of-Study [ Time Frame: 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1)) ]
    A urinary pregnancy test will be 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.

  19. Serious Adverse Events [ Time Frame: Signing of Informed Consent at Screening Visit to End-of-Study Visit, an expected average of 7 Weeks ]
    Adverse drug events (ADEs), whether observed by investigators or reported by the subjects, will be documented, evaluated, followed up, and treated if deemed necessary. According to FDA guidelines, a serious ADE will refer to any adverse drug experience occurring at any dose that results in any of the following outcomes: 1) death; 2) a life-threatening adverse drug experience; 3) inpatient hospitalization or prolongation of existing hospitalization; 4) persistent or significant disability/incapacity; 5) congenital anomaly/birth defect; 6) other important medical events that may jeopardize the subject or may require medical or surgical intervention to prevent one of the outcomes listed in this definition. ADEs will be followed until stabilized/resolved or 30 days from the date the subject has finished the study, whichever is sooner.

  20. Other Adverse Events [ Time Frame: Signing of Informed Consent at Screening Visit to End-of-Study Visit, an expected average of 7 Weeks ]
    Adverse drug events (ADEs), whether observed by investigators or reported by the subjects, will be documented, evaluated, followed up, and treated if deemed necessary. ADEs will be followed until stabilized/resolved or 30 days from the date the subject has finished the study, whichever is sooner.



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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Generally healthy, male and female adults, 18-40 years of age at Screening;
  • Having no clinically significant respiratory, cardiovascular and other systemic or organic illnesses;
  • 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 HIV, HBsAg and HCV tests, alcohol and nine panel urine drug screen tests;
  • Demonstrating proficiency in the use of DPI and MDI or able to be trained in the proper use of these devices;
  • 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;
  • Having no known hypersensitivity to any ingredients of A006 and Proventil® MDI (Albuterol, sulfate, lactose, milk protein, HFA-134a, oleic acid, or ethanol). (Subjects must be able to tolerate at least one teaspoon of milk);
  • Women of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control; and
  • Having properly consented and satisfied all other inclusion/exclusion criteria as required for this protocol.

Exclusion Criteria:

  • A smoking history of ≥ 5 pack-years, or having smoked within 6 months prior to Screening;
  • Upper respiratory tract infections within 2 weeks, or lower respiratory tract infection within 4 weeks, prior to Screening;
  • Previous history of asthma or COPD;
  • 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;
  • Concurrent clinically significant cardiovascular, 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;
  • ECG at Screening and Visit-1 baseline expressed any single or multiple premature ventricular contractions (PVC);
  • ECG at Screening and Visit-1 baseline with a QTc reading greater than 450ms;
  • Use of prohibited drugs or failure to observe the drug washout restrictions; and
  • Having been on other clinical drug/device studies or donated blood 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): NCT02271334


Locations
United States, California
Amphastar Site 0035
Cypress, California, United States, 90630
Sponsors and Collaborators
Amphastar Pharmaceuticals, Inc.
Investigators
Study Director: Safety Monitor Amphastar Pharmeceuticals, Inc.

Publications:
Responsible Party: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02271334     History of Changes
Other Study ID Numbers: API-A006-CL-D
First Posted: October 22, 2014    Key Record Dates
Last Update Posted: April 19, 2017
Last Verified: April 2017

Keywords provided by Amphastar Pharmaceuticals, Inc.:
Asthma
Albuterol

Additional relevant MeSH terms:
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