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

NCT01189396 | Completed Phase 2

• 1 other identifier: API-A006-CL-C
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 4

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.

Conditions

Asthma; Bronchospasm; Chronic Obstructive Pulmonary Disease (COPD)

Keywords

asthma; bronchospasm; COPD; reversibility; efficacy

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (6)

• AUC0-t of change in FEV1

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

• Time to onset

  0 - 120 min

• Peak Response

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

• Adverse Events

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

• Blood Analysis

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

Study Arms (3)

T

EXPERIMENTAL

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.

Drug: A006

R

ACTIVE COMPARATOR

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.

Drug: Proventil-HFA

P

PLACEBO COMPARATOR

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.

Drug: Placebo DPI

Interventions

A006 DRUG

Albuterol DPI with 180 mcg Albuterol/inhalation

T

Placebo DPI DRUG

Placebo DPI with 0 mcg Albuterol/inhalation

P

Proventil-HFA DRUG

Albuterol MDI with 90 mcg Albuterol/inhalation

R

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amphastar Pharmaceuticals, Inc.: lead

Study Sites (4)

Amphastar Site 0025

Medford, Oregon, 97504, United States

Location

Amphastar Site 0026

Portland, Oregon, 97213, United States

Location

Amphastar Site 0032

San Antonio, Texas, 78229, United States

Location

Amphastar Site 0034

Seattle, Washington, 98105, United States

Location

Related Publications (7)

• 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.

  PMID: 16185368 BACKGROUND

• 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.

  PMID: 3653233 BACKGROUND

• 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.

  PMID: 7874928 BACKGROUND

• 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.

  PMID: 15994402 BACKGROUND

• 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.

  PMID: 16264058 BACKGROUND

• 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.

  PMID: 7271065 BACKGROUND

• 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.

  PMID: 7074238 BACKGROUND

MeSH Terms

Conditions

Asthma; Bronchial Spasm; Pulmonary Disease, Chronic Obstructive

Interventions

OIC-A006; Albuterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Study Officials

• Safety Monitor

  Amphastar Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2010
• First Posted: August 26, 2010
• Study Start: July 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: January 1, 2011
• Last Updated: July 2, 2017

Record last verified: 2017-06

Locations

US (4)