Evaluation of Pharmacokinetics and Safety of A006 in Healthy Volunteers

NCT02271334 | Completed Phase 2 DMC

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

Brief Summary

The objective of this study is to evaluate the pharmacokinetics (PK) and safety profiles of A006, an Albuterol dry powder inhaler (DPI), following a single dose of 110 mcg (T1) or 220 mcg (T2), in healthy male and female adult volunteers.

Conditions

Asthma

Keywords

Asthma; Albuterol

Outcome Measures

Primary Outcomes (4)

• Area Under the Curve of Drug Concentration versus Time (AUC[0-t])

  Subject PK blood samples will be taken prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. PK samples will be analyzed using a validated test method. Area under the curve of the drug concentration versus time curve (AUC\[0-t\]) for each treatment period will be calculated using the trapezoidal rule.

  Within 30 minutes prior to dosing (baseline) to 8 hours post-dose

• Peak Plasma Concentration (C[max])

  Subject PK blood samples will be taken prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. PK samples will be analyzed using a validated test method. Peak plasma concentration (C\[max\]) will be the highest concentration of Albuterol during each treatment period.

  Within 30 minutes prior to dosing (baseline) to 8 hours post-dose

• Time to Reach Peak Plasma Concentration (t[max])

  Subject PK blood samples will be taken prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. PK samples will be analyzed using a validated test method. Time to reach peak plasma concentration (t\[max\]) will be the time it takes to reach the highest concentration of Albuterol during each treatment period.

  Within 30 minutes prior to dosing (baseline) to 8 hours post-dose

• Plasma Albuterol Concentrations at All Time Points

  Subject PK blood samples will be taken prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. PK samples will be analyzed using a validated test method. Plasma Albuterol concentrations at these time points will be reported during each treatment period.

  Within 30 minutes prior to dosing (baseline) to 8 hours post-dose

Other Outcomes (20)

• Systolic Blood Pressure (SBP) at Screening

  Within 14 days prior to Day 1 (Visit 1)

• Systolic Blood Pressure (SBP)

  Within 30 minutes prior to dosing (baseline) to 8 hours post-dose

• Diastolic Blood Pressure (DBP) at Screening

  Within 14 days prior to Day 1 (Visit 1)

Study Arms (4)

Treatment T1

EXPERIMENTAL

One inhalation of 110 mcg A006 DPI. Total 110 mcg

Drug: A006 DPI

Treatment T2

EXPERIMENTAL

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

Drug: A006 DPI

Treatment R1

ACTIVE COMPARATOR

One inhalation of 90 mcg Proventil® MDI. Total 90 mcg.

Drug: Proventil® MDI

Treatment R2

ACTIVE COMPARATOR

Two inhalations of 90 mcg Proventil® MDI. Total 180 mcg

Drug: Proventil® MDI

Interventions

A006 DPI DRUG

Single dose 110 mcg, 1 inhalation

Also known as: Albuterol, Albuterol DPI

Treatment T1

Proventil® MDI DRUG

Single dose 90 mcg, 1 inhalation

Also known as: Proventil®

Treatment R1

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Generally healthy, male and female adults, 18-40 years of age at Screening;
• Having no clinically significant respiratory, cardiovascular and other systemic or organic illnesses;
• 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 HIV, HBsAg and HCV tests, alcohol and nine panel urine drug screen tests;
• Demonstrating proficiency in the use of DPI and MDI or able to be trained in the proper use of these devices;
• 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;
• Having no known hypersensitivity to any ingredients of A006 and Proventil® MDI (Albuterol, sulfate, lactose, milk protein, HFA-134a, oleic acid, or ethanol). (Subjects must be able to tolerate at least one teaspoon of milk);
• Women of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control; and

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 within 2 weeks, or lower respiratory tract infection within 4 weeks, prior to Screening;
• Previous history of asthma or COPD;
• 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;
• Concurrent clinically significant cardiovascular, 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;
• ECG at Screening and Visit-1 baseline expressed any single or multiple premature ventricular contractions (PVC);
• ECG at Screening and Visit-1 baseline with a QTc reading greater than 450ms;
• Use of prohibited drugs or failure to observe the drug washout restrictions; and
• Having been on other clinical drug/device studies or donated blood in the last 30 days prior to Screening.

Sponsors & Collaborators

• Amphastar Pharmaceuticals, Inc.: lead

Study Sites (1)

Amphastar Site 0035

Cypress, California, 90630, United States

Location

Related Publications (4)

• 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

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: October 20, 2014
• First Posted: October 22, 2014
• Study Start: August 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: March 1, 2015
• Last Updated: April 19, 2017

Record last verified: 2017-04

Locations

US (1)