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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01189396
• Other study ID #: API-A006-CL-C
• Status: Completed
• Phase: Phase 2
• First received: August 24, 2010
• Last updated: June 27, 2017
• Start date: July 2010
• Est. completion date: January 2011

Study information

• Verified date: June 2017
• Source: Amphastar Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: January 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Asthma
• Bronchial Spasm
• Bronchospasm
• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• A006
Albuterol DPI with 180 mcg Albuterol/inhalation
• Placebo DPI
Placebo DPI with 0 mcg Albuterol/inhalation
• Proventil-HFA
Albuterol MDI with 90 mcg Albuterol/inhalation

Locations

Country	Name	City	State
United States	Amphastar Site 0025	Medford	Oregon
United States	Amphastar Site 0026	Portland	Oregon
United States	Amphastar Site 0032	San Antonio	Texas
United States	Amphastar Site 0034	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Amphastar Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

References & 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. Review. — View 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. — View 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. — View 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. — View 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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	-15, 15 min post 1, 2, and 3, and 15, 90, 120, 240, and 360min post dose 4
Secondary	Time to onset	Time to onset of bronchodilatory effect, determined by linear interpolation as the point where FEV1 % change first reaches = 12% from FEV10.	0 - 120 min
Secondary	Peak Response	The peak bronchodilator response, defined as the maximum post-dose FEV1 % change. Doses are at time 0, 30, 60, and 90 min.	15 min post dose 1, 2 and 3 and 15, 45, 90, 120, 180, 240, and 360 min post dose 4
Secondary	Adverse Events	The adverse drug events (ADE) that are observed with Proventil-HFA may be expected with the use of A006	Time 0, 15, 45, 75, 105, 150, 195, 130, 190, 250, 435 minutes post dose 1
Secondary	Blood Analysis	serum glucose and potassium analysis and PK analysis	-15, 10, 25,40, 55, 70, 85, 95, 115, 145, 175, 210, 270, 330, 690 min post dose 1
Secondary	Vital Signs and Electrocardiogram (ECG)	vital signs, including pulse and blood pressure and 12-lead ECG	-15, 5, 35, 65, 100, 155, 275, 455, 815 min post dose 1