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

Purpose

The main objective is to evaluate the bronchodilatory efficacy, safety and pharmacokinetic profiles of A006, in comparison with those of an active control, Proventil®-HFA MDI, and a placebo control DPI, in escalating and cumulative-doses up to 1,440 mcg, eight (8) times of the proposed clinical dose.

Condition	Intervention	Phase
Asthma Bronchospasm Chronic Obstructive Pulmonary Disease (COPD)	Drug: Albuterol Inhalation Powder Drug: Placebo Control Drug: Active Comparator	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Asthma COPD (Chronic Obstructive Pulmonary Disease)

Drug Information available for: Albuterol Levalbuterol Levalbuterol hydrochloride Albuterol sulfate Levalbuterol tartrate

U.S. FDA Resources

Further study details as provided by Amphastar Pharmaceuticals, Inc.:

Primary Outcome Measures:

Bronchodilatory efficacy after the escalating and cumulative-doses, up to 1,440 mcg. [ 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 ] [ Designated as safety issue: No ]
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 [ Time Frame: -15, 15 min post 1, 2, and 3, and 15, 90, 120, 240, and 360min post dose 4 ] [ Designated as safety issue: No ]
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 Frame: 0 - 120 min ] [ Designated as safety issue: No ]
Time to onset of bronchodilatory effect, determined by linear interpolation as the point where FEV1 % change first reaches ≥ 12% from FEV10.
Peak Response [ Time Frame: 15 min post dose 1, 2 and 3 and 15, 45, 90, 120, 180, 240, and 360 min post dose 4 ] [ Designated as safety issue: No ]
The peak bronchodilator response, defined as the maximum post-dose FEV1 % change. Doses are at time 0, 30, 60, and 90 min.
Adverse Events [ Time Frame: Time 0, 15, 45, 75, 105, 150, 195, 130, 190, 250, 435 minutes post dose 1 ] [ Designated as safety issue: Yes ]
The adverse drug events (ADE) that are observed with Albuterol MDI may be expected with the use of Albuterol DPI
Blood Analysis [ Time Frame: -15, 10, 25,40, 55, 70, 85, 95, 115, 145, 175, 210, 270, 330, 690 min post dose 1 ] [ Designated as safety issue: Yes ]
serum glucose and potassium analysis and PK analysis
Vital Signs and Electrocardiogram (ECG) [ Time Frame: -15, 5, 35, 65, 100, 155, 275, 455, 815 min post dose 1 ] [ Designated as safety issue: Yes ]
vital signs, including pulse and blood pressure and 12-lead ECG

Enrollment:	27
Study Start Date:	July 2010
Study Completion Date:	January 2011
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment 1 Albuterol Inhalation Powder escalating dose up to 180 mcg/dose, cumulative dose up to 1440 mcg, dosing at 30 min. intervals	Drug: Albuterol Inhalation Powder Albuterol dry powder inhaler, 180 mcg/inhalation, escalating dose 180 mcg, 180 mcg, 360 mcg, 720 mcg, at 30 min intervals, total cumulative dose 1440 Other Name: A006
Active Comparator: Active Control Proventil HFA albuterol inhalation aerosol, 90 mcg/ inhalation	Drug: Active Comparator Proventil HFA albuterol inhalation aerosol, 90 mcg/inhalation, 2, 2, 4, and 8 inhalations per dose a 30 min intervals, total accumulated dose 1440 mcg. Other Name: albuterol inhalation aerosol HFA
Placebo Comparator: Placebo Control Placebo control, 0 mcg albuterol/dose, contains only lactose as carrier.	Drug: Placebo Control Placebo control contains only lactose in amounts identical to the lactose contained in A006. 1, 1, 2, and 4 inhalation at 30 min intervals.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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® MDI;
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 study drug DPI or Proventil® MDI;
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01189396

Locations

United States, Oregon
Amphastar Site 4
Medford, Oregon, United States, 97504
Amphastar Site 1
Portland, Oregon, United States, 97212
United States, Texas
Ampahstar Site 3
San Antonio, Texas, United States, 78229
United States, Washington
Ampahstar Site 2
Seattle, Washington, United States, 98105

Sponsors and Collaborators

Amphastar Pharmaceuticals, Inc.

Investigators

Study Director:

Medical Director, M.D., Ph.D.

Amphastar Pharmaceuticals, Inc.

More Information

Publications:

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.

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.

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. Review. No abstract available.

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. No abstract available.

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.

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.

Responsible Party:	Medical Director, Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01189396 History of Changes
Other Study ID Numbers:	API-A006-CL-C
Study First Received:	August 24, 2010
Last Updated:	January 23, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Amphastar Pharmaceuticals, Inc.:

asthma
bronchospasm
COPD
reversibility
efficacy

Additional relevant MeSH terms:

Asthma
Bronchial Spasm
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Albuterol
Tocolytic Agents
Reproductive Control Agents

Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on May 16, 2013