Albuterol DPI (A006) Clinical Study-B3:Efficacy, Dose-ranging and Safety Evaluation

NCT02210806 | Completed Phase 2

• 1 other identifier: API-A006-CL-B3
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

Brief Summary

This study evaluates the efficacy, dose-ranging and safety profiles of A006, an Albuterol dry powder inhaler (DPI), in the dose range of 110 to 220 mcg per dose in comparison to a DPI Placebo Control and an Albuterol metered dose inhaler (MDI) Active Control.

Conditions

Asthma

Keywords

Asthma; Mild-to-moderate persistent asthma; Mild asthma; Moderate asthma; Persistent asthma

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 Percentage Change (∆%FEV1) from the Same-Day Pre-Dose Baseline

  The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Area under the curve (AUC), from baseline to 6 hours post-dose, for the treatment period is calculated using the trapezoidal rule. Statistical analysis is performed using a one-sided t-test.

  Within 30 minutes prior to dosing (baseline) to 6 hours post-dose

Secondary Outcomes (12)

• Area Under the Curve (AUC[0-6h]) of Placebo Adjusted Post-Dose FEV1 Percentage Change (∆∆%FEV1) from the Same-Day Pre-Dose Baseline

  Within 30 minutes prior to dosing (baseline) to 6 hours post-dose

• Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 Volume Changes (∆FEV1) from the Same-Day Pre-Dose Baseline

  Within 30 minutes prior to dosing (baseline) to 6 hours post-dose

• Time to Onset of Bronchodilator Effect (t[onset])

  Within 30 minutes prior to dosing (baseline) to 6 hours post-dose

• Peak Bronchodilator Response (F[max])

  Within 30 minutes prior to dosing (baseline) to 6 hours post-dose

• Time to Peak ∆FEV1 Effect (t[max])

  Within 30 minutes prior to dosing (baseline) to 6 hours post-dose

Other Outcomes (17)

• Systolic and Diastolic Blood Pressure (SBP/DBP) at Screening

  Within 30 minutes prior to reversibility dosing (baseline) and 30 minutes post-reversibility dosing

• Systolic and Diastolic Blood Pressure (SBP/DBP)

  Within 1 hour prior to dosing (baseline) to 6 hours post-dose

• Heart Rate (HR) at Screening

  Within 30 minutes prior to reversibility dosing (baseline) and 30 minutes post-reversibility dosing

Study Arms (5)

Treatment T1

ACTIVE COMPARATOR

One inhalation of 110 mcg A006 DPI. Total 110 mcg.

Drug: A006 DPI

Treatment T2

ACTIVE COMPARATOR

One inhalation of 220 mcg A006 DPI. Total 220 mcg.

Drug: A006 DPI

Placebo

PLACEBO COMPARATOR

One inhalation of placebo DPI . Total 0 mcg

Other: Placebo DPI

Treatment R1

ACTIVE COMPARATOR

One inhalation of Proventil® MDI Total 90 mcg

Drug: Proventil® MDI

Treatment R2

ACTIVE COMPARATOR

Two inhalations of Proventil® MDI, 180 mcg total

Drug: Proventil® MDI

Interventions

A006 DPI DRUG

Single dose 110 mcg, 1 inhalation

Also known as: Albuterol, Albuterol DPI

Treatment T1

Placebo DPI OTHER

Placebo, 1 inhalation

Also known as: Placebo

Placebo

Proventil® MDI DRUG

Single dose 90 mcg, 1 inhalation

Also known as: Proventil®

Treatment R1

Eligibility Criteria

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

You may qualify if:

• Generally healthy, male and female adults, 18-55 years of age at Screening
• 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 Screening Baseline FEV1 at 50.0 - 85.0% of predicted normal
• Demonstrating a ≥ 15.0% Airway Reversibility in FEV1 within 30 min after inhaling 2 actuations of Proventil® MDI (180 mcg) at Screening
• Demonstrating Peak Inspiratory Flow Rate (PIF) within 80-150 L/min (after training), for at least 2 times consecutively with a maximum of 5 attempts
• Demonstrating proficiency in the use of a DPI and an MDI after training
• Females of child-bearing potential must be non-pregnant, non-lactating; both males and females enrolled into the study must agree to practice a clinically acceptable form of birth control (including but not limited to, abstinence, double barrier, etc)
• Having properly consented to participate in the trial

You may not qualify if:

• A smoking history of ≥ 5 pack-years, or having smoked within 6 months prior to Screening
• Upper respiratory tract infections or lower respiratory tract infection within 6 weeks, prior to Screening
• Asthma exacerbations that required emergency care or hospitalized treatment, within 4 weeks prior to Screening
• Any current or recent respiratory conditions that, per investigator discretion, might significantly affect pharmacodynamic response to the study drugs, including cystic fibrosis, bronchiectasis, tuberculosis, emphysema, and other significant respiratory diseases besides asthma
• Concurrent clinically significant cardiovascular (e.g. hypertension and tachyarrhythmia and bradyarrhythmia), hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignant, or other illnesses that in the opinion of the investigator 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® HFA MDI (i.e., Albuterol, sulfate, lactose, milk protein, HFA-134a, oleic acid, and ethanol)
• Baseline ECG at Screening or Visit 1 showing any single or multiple premature ventricular contractions (PVC)
• Baseline ECG at Screening or Visit 1 with a confirmed (through performing a second ECG) QTc reading greater than 450ms
• 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 prior to Screening.

Sponsors & Collaborators

• Amphastar Pharmaceuticals, Inc.: lead

Study Sites (4)

Amphastar Site 0001

San Jose, California, 95117, United States

Location

Amphastar Site 0025

Medford, Oregon, 97504, United States

Location

Amphastar Site 0030

New Braunfels, Texas, 78130, United States

Location

Amphastar Site 0032

San Antonio, Texas, 78229, United States

Location

Related Publications (7)

• Lipworth BJ, Clark DJ. Lung delivery of salbutamol given by breath activated pressurized aerosol and dry powder inhaler devices. Pulm Pharmacol Ther. 1997 Aug;10(4):211-4. doi: 10.1006/pupt.1997.0093.

  PMID: 9695144 BACKGROUND

• 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

• 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

Interventions

Albuterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Safety Monitor

  Amphastar Pharmeceuticals, Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 4, 2014
• First Posted: August 7, 2014
• Study Start: July 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: October 1, 2014
• Last Updated: April 19, 2017

Record last verified: 2017-04

Locations

US (4)