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

Condition(s) targeted: Asthma; Bronchospasm; Chronic Obstructive Pulmonary Disease (COPD)

Intervention: Albuterol Inhalation Powder (Drug); Placebo Control (Drug); Active Comparator (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Amphastar Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
Medical Director, M.D., Ph.D., Study Director, Affiliation: Amphastar Pharmaceuticals, Inc.

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.

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

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

Secondary outcome:

AUC0-t of change in FEV1

Time to onset

Peak Response

Adverse Events

Blood Analysis

Vital Signs and Electrocardiogram (ECG)

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

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.

Amphastar Site 4, Medford, Oregon 97504, United States

Amphastar Site 1, Portland, Oregon 97212, United States

Ampahstar Site 3, San Antonio, Texas 78229, United States

Ampahstar Site 2, Seattle, Washington 98105, United States

Related publications:

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. Review.

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.

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.

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.

Starting date: July 2010
Last updated: January 23, 2012