Clinical trial NCT01189396: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Bronchospasm
Chronic Obstructive Pulmonary Disease (COPD)
Keywords: asthma
bronchospasm
COPD
reversibility
efficacy
Lead sponsor: Amphastar Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2010-08-26
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Bronchodilatory efficacy after the escalating and cumulative-doses, up to 1,440 mcg.
timeFrame: -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:
measure: AUC0-t of change in FEV1
timeFrame: -15, 15 min post 1, 2, and 3, and 15, 90, 120, 240, and 360min post dose 4
measure: Time to onset
timeFrame: 0 - 120 min
measure: Peak Response
timeFrame: 15 min post dose 1, 2 and 3 and 15, 45, 90, 120, 180, 240, and 360 min post dose 4
measure: Adverse Events
timeFrame: Time 0, 15, 45, 75, 105, 150, 195, 130, 190, 250, 435 minutes post dose 1
measure: Blood Analysis
timeFrame: -15, 10, 25,40, 55, 70, 85, 95, 115, 145, 175, 210, 270, 330, 690 min post dose 1
measure: Vital Signs and Electrocardiogram (ECG)
timeFrame: -15, 5, 35, 65, 100, 155, 275, 455, 815 min post dose 1
Other outcomes:
Locations:
city: Medford
country: United States
facility: Amphastar Site 0025
state: Oregon
city: Portland
country: United States
facility: Amphastar Site 0026
state: Oregon
city: San Antonio
country: United States
facility: Amphastar Site 0032
state: Texas
city: Seattle
country: United States
facility: Amphastar Site 0034
state: Washington
Study officials:
affiliation: Amphastar Pharmaceuticals, Inc.
name: Safety Monitor
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.
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.
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.