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

Primary Purpose

Asthma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
A006 DPI
A006 DPI
Proventil® MDI
Proventil® MDI
Sponsored by
Amphastar Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma focused on measuring Asthma, Albuterol

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Amphastar Site 0035

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Active Comparator

Active Comparator

Arm Label

Treatment T1

Treatment T2

Treatment R1

Treatment R2

Arm Description

One inhalation of 110 mcg A006 DPI. Total 110 mcg

One inhalation of 220 mcg A006 DPI. Total 220 mcg.

One inhalation of 90 mcg Proventil® MDI. Total 90 mcg.

Two inhalations of 90 mcg Proventil® MDI. Total 180 mcg

Outcomes

Primary Outcome Measures

Area Under the Curve of Drug Concentration versus Time (AUC[0-t])
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.
Peak Plasma Concentration (C[max])
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.
Time to Reach Peak Plasma Concentration (t[max])
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.
Plasma Albuterol Concentrations at All Time Points
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.

Secondary Outcome Measures

Full Information

First Posted
October 20, 2014
Last Updated
April 17, 2017
Sponsor
Amphastar Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02271334
Brief Title
Evaluation of Pharmacokinetics and Safety of A006 in Healthy Volunteers
Acronym
A006-D
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 Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amphastar Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Asthma, Albuterol

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment T1
Arm Type
Experimental
Arm Description
One inhalation of 110 mcg A006 DPI. Total 110 mcg
Arm Title
Treatment T2
Arm Type
Experimental
Arm Description
One inhalation of 220 mcg A006 DPI. Total 220 mcg.
Arm Title
Treatment R1
Arm Type
Active Comparator
Arm Description
One inhalation of 90 mcg Proventil® MDI. Total 90 mcg.
Arm Title
Treatment R2
Arm Type
Active Comparator
Arm Description
Two inhalations of 90 mcg Proventil® MDI. Total 180 mcg
Intervention Type
Drug
Intervention Name(s)
A006 DPI
Other Intervention Name(s)
Albuterol, Albuterol DPI
Intervention Description
Single dose 110 mcg, 1 inhalation
Intervention Type
Drug
Intervention Name(s)
A006 DPI
Other Intervention Name(s)
Albuterol, Albuterol DPI
Intervention Description
Single dose 220 mcg, 1 inhalation
Intervention Type
Drug
Intervention Name(s)
Proventil® MDI
Other Intervention Name(s)
Proventil®
Intervention Description
Single dose 90 mcg, 1 inhalation
Intervention Type
Drug
Intervention Name(s)
Proventil® MDI
Other Intervention Name(s)
Proventil®
Intervention Description
Single dose 90 mcg, 2 inhalations
Primary Outcome Measure Information:
Title
Area Under the Curve of Drug Concentration versus Time (AUC[0-t])
Description
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.
Time Frame
Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
Title
Peak Plasma Concentration (C[max])
Description
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.
Time Frame
Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
Title
Time to Reach Peak Plasma Concentration (t[max])
Description
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.
Time Frame
Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
Title
Plasma Albuterol Concentrations at All Time Points
Description
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.
Time Frame
Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
Other Pre-specified Outcome Measures:
Title
Systolic Blood Pressure (SBP) at Screening
Description
Subjects will have their vital signs, i.e., blood pressure and heart rate, measured during the Screening Visit to ensure they are generally healthy.
Time Frame
Within 14 days prior to Day 1 (Visit 1)
Title
Systolic Blood Pressure (SBP)
Description
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.
Time Frame
Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
Title
Diastolic Blood Pressure (DBP) at Screening
Description
Subjects will have their vital signs, i.e., blood pressure and heart rate, measured during the Screening Visit to ensure they are generally healthy.
Time Frame
Within 14 days prior to Day 1 (Visit 1)
Title
Diastolic Blood Pressure (DBP)
Description
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.
Time Frame
Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
Title
Heart Rate (HR) at Screening
Description
Subjects will have their vital signs, i.e., blood pressure and heart rate, measured during the Screening Visit to ensure they are generally healthy.
Time Frame
Within 14 days prior to Day 1 (Visit 1)
Title
Heart Rate (HR)
Description
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.
Time Frame
Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
Title
12-Lead ECG QT Intervals at Screening
Description
12-Lead ECGs will be performed to measure QT and QTc intervals during the Screening Visit to ensure absence of overt cardiac illnesses.
Time Frame
Within 14 days prior to Day 1 (Visit 1)
Title
12-Lead ECG QT Intervals
Description
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.
Time Frame
Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
Title
12-Lead ECG QTc Intervals at Screening
Description
12-Lead ECGs will be performed to measure QT and QTc intervals during the Screening Visit to ensure absence of overt cardiac illnesses.
Time Frame
Within 14 days prior to Day 1 (Visit 1)
Title
12-Lead ECG QTc Intervals
Description
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.
Time Frame
Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
Title
Complete Blood Count (CBC) at Screening
Description
A CBC will be performed as part of the subject safety evaluations at screening.
Time Frame
Within 14 days prior to Day 1 (Visit 1)
Title
Complete Blood Count (CBC) at End-of-Study
Description
A CBC will be performed as part of the End-of-Study subject safety evaluations at end-of-study.
Time Frame
4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1))
Title
Comprehensive Metabolic Panel (CMP) at Screening
Description
A CMP will be performed as part of the subject safety evaluations at screening.
Time Frame
Within 14 days prior to Day 1 (Visit 1)
Title
Comprehensive Metabolic Panel (CMP) at End-of-Study
Description
A CMP will be performed as part of the End-of-Study subject safety evaluations at end-of-study.
Time Frame
4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1))
Title
Urinalysis at Screening
Description
Routine and microscopic urinalysis will be performed as part of the subject safety evaluations at screening.
Time Frame
Within 14 days prior to Day 1 (Visit 1)
Title
Urinalysis at End-of-Study
Description
Routine and microscopic urinalysis will be performed as part of the End-of-Study subject safety evaluations at end-of-study.
Time Frame
4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1))
Title
Incidents of Pregnancy at Screening
Description
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.
Time Frame
Within 14 days prior to Day 1 (Visit 1)
Title
Incidents of Pregnancy at End-of-Study
Description
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.
Time Frame
4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1))
Title
Serious Adverse Events
Description
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.
Time Frame
Signing of Informed Consent at Screening Visit to End-of-Study Visit, an expected average of 7 Weeks
Title
Other Adverse Events
Description
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.
Time Frame
Signing of Informed Consent at Screening Visit to End-of-Study Visit, an expected average of 7 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Safety Monitor
Organizational Affiliation
Amphastar Pharmeceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Amphastar Site 0035
City
Cypress
State/Province
California
ZIP/Postal Code
90630
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9695144
Citation
Lipworth BJ, Clark DJ. Lung delivery of salbutamol given by breath activated pressurized aerosol and dry powder inhaler devices. Pulm Pharmacol Ther. 1997 Aug;10(4):211-4. doi: 10.1006/pupt.1997.0093.
Results Reference
background
PubMed Identifier
16185368
Citation
Ahrens RC. The role of the MDI and DPI in pediatric patients: "Children are not just miniature adults". Respir Care. 2005 Oct;50(10):1323-8; discussion 1328-30.
Results Reference
background
PubMed Identifier
3653233
Citation
Goldstein DA, Tan YK, Soldin SJ. Pharmacokinetics and absolute bioavailability of salbutamol in healthy adult volunteers. Eur J Clin Pharmacol. 1987;32(6):631-4. doi: 10.1007/BF02456001.
Results Reference
background
PubMed Identifier
7874928
Citation
Hindle M, Newton DA, Chrystyn H. Dry powder inhalers are bioequivalent to metered-dose inhalers. A study using a new urinary albuterol (salbutamol) assay technique. Chest. 1995 Mar;107(3):629-33. doi: 10.1378/chest.107.3.629.
Results Reference
background

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Evaluation of Pharmacokinetics and Safety of A006 in Healthy Volunteers

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