Back to results

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

Primary Purpose

Asthma, Bronchospasm, Chronic Obstructive Pulmonary Disease (COPD)

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

A006

Placebo DPI

Proventil-HFA

About this trial

This is an interventional treatment trial for Asthma focused on measuring asthma, bronchospasm, COPD, reversibility, efficacy

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Amphastar Site 0025
Amphastar Site 0026
Amphastar Site 0032
Amphastar Site 0034

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Bronchodilatory efficacy after the escalating and cumulative-doses, up to 1,440 mcg.

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

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 to onset of bronchodilatory effect, determined by linear interpolation as the point where FEV1 % change first reaches ≥ 12% from FEV10.

Peak Response

The peak bronchodilator response, defined as the maximum post-dose FEV1 % change. Doses are at time 0, 30, 60, and 90 min.

Adverse Events

The adverse drug events (ADE) that are observed with Proventil-HFA may be expected with the use of A006

Blood Analysis

serum glucose and potassium analysis and PK analysis

Vital Signs and Electrocardiogram (ECG)

vital signs, including pulse and blood pressure and 12-lead ECG

Full Information

NCT ID

NCT01189396

First Posted

August 24, 2010

Last Updated

June 27, 2017

Sponsor

Amphastar Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01189396

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Completed

Study Start Date

July 2010 (undefined)

Primary Completion Date

December 2010 (Actual)

Study Completion Date

January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amphastar Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

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

Asthma, Bronchospasm, Chronic Obstructive Pulmonary Disease (COPD)

Keywords

asthma, bronchospasm, COPD, reversibility, efficacy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

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.

Arm Title

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

A006

Intervention Description

Albuterol DPI with 180 mcg Albuterol/inhalation

Intervention Type

Drug

Intervention Name(s)

Placebo DPI

Intervention Description

Placebo DPI with 0 mcg Albuterol/inhalation

Intervention Type

Drug

Intervention Name(s)

Proventil-HFA

Intervention Description

Albuterol MDI with 90 mcg Albuterol/inhalation

Primary Outcome Measure Information:

Title

Bronchodilatory efficacy after the escalating and cumulative-doses, up to 1,440 mcg.

Description

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

Secondary Outcome Measure Information:

Title

AUC0-t of change in FEV1

Description

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 Frame

-15, 15 min post 1, 2, and 3, and 15, 90, 120, 240, and 360min post dose 4

Title

Time to onset

Description

Time to onset of bronchodilatory effect, determined by linear interpolation as the point where FEV1 % change first reaches ≥ 12% from FEV10.

Time Frame

0 - 120 min

Title

Peak Response

Description

The peak bronchodilator response, defined as the maximum post-dose FEV1 % change. Doses are at time 0, 30, 60, and 90 min.

Time Frame

15 min post dose 1, 2 and 3 and 15, 45, 90, 120, 180, 240, and 360 min post dose 4

Title

Adverse Events

Description

The adverse drug events (ADE) that are observed with Proventil-HFA may be expected with the use of A006

Time Frame

Time 0, 15, 45, 75, 105, 150, 195, 130, 190, 250, 435 minutes post dose 1

Title

Blood Analysis

Description

serum glucose and potassium analysis and PK analysis

Time Frame

-15, 10, 25,40, 55, 70, 85, 95, 115, 145, 175, 210, 270, 330, 690 min post dose 1

Title

Vital Signs and Electrocardiogram (ECG)

Description

vital signs, including pulse and blood pressure and 12-lead ECG

Time Frame

-15, 5, 35, 65, 100, 155, 275, 455, 815 min post dose 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Safety Monitor

Organizational Affiliation

Amphastar Pharmaceuticals, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Amphastar Site 0025

City

Medford

State/Province

Oregon

ZIP/Postal Code

97504

Country

United States

Facility Name

Amphastar Site 0026

City

Portland

State/Province

Oregon

ZIP/Postal Code

97213

Country

United States

Facility Name

Amphastar Site 0032

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

Amphastar Site 0034

City

Seattle

State/Province

Washington

ZIP/Postal Code

98105

Country

United States

12. IPD Sharing Statement

Citations:

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

PubMed Identifier

15994402

Citation

Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. General considerations for lung function testing. Eur Respir J. 2005 Jul;26(1):153-61. doi: 10.1183/09031936.05.00034505. No abstract available.

Results Reference

background

PubMed Identifier

16264058

Citation

Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, Coates A, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson DC, MacIntyre N, McKay R, Miller MR, Navajas D, Pedersen OF, Wanger J. Interpretative strategies for lung function tests. Eur Respir J. 2005 Nov;26(5):948-68. doi: 10.1183/09031936.05.00035205. No abstract available.

Results Reference

background

PubMed Identifier

7271065

Citation

Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981 Jun;123(6):659-64. doi: 10.1164/arrd.1981.123.6.659.

Results Reference

background

PubMed Identifier

7074238

Citation

Crapo RO, Morris AH, Clayton PD, Nixon CR. Lung volumes in healthy nonsmoking adults. Bull Eur Physiopathol Respir. 1982 May-Jun;18(3):419-25.

Results Reference

background

Learn more about this trial

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

We'll reach out to this number within 24 hrs