Evaluation of Pharmacokinetics and Safety of A006 in Healthy Volunteers

Phase 2

Completed

Conditions: Asthma

Interventions: Drug: A006 DPI
Drug: Proventil® MDI

Registration Number: NCT02271334

Lead Sponsor: Amphastar Pharmaceuticals, Inc.

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.

Detailed Description: This study is a randomized, double or evaluator-blinded, single dose, four-arm, crossover PK study in eighteen (18) healthy volunteers, both male and female adults, at 18-40 years of age.

All candidates will be screened and only those who satisfy all enrollment criteria will be enrolled into this study. Each study subject will participate in a screening visit and four (4) study visits with one (1) randomized study treatment given in each visit.

PK samples will be analyzed with an established LC/MS/MS method. An End-of-Study (EOS) safety evaluation will be conducted at the end of Study Visit-4.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 22

Inclusion Criteria

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
Having properly consented and satisfied all other inclusion/exclusion criteria as required for this protocol.

Exclusion Criteria

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment T1	A006 DPI	One inhalation of 110 mcg A006 DPI. Total 110 mcg
Treatment R1	Proventil® MDI	One inhalation of 90 mcg Proventil® MDI. Total 90 mcg.
Treatment T2	A006 DPI	One inhalation of 220 mcg A006 DPI. Total 220 mcg.
Treatment R2	Proventil® MDI	Two inhalations of 90 mcg Proventil® MDI. Total 180 mcg

Primary Outcome Measures

Name	Time	Method
Plasma Albuterol Concentrations at All Time Points	Within 30 minutes prior to dosing (baseline) to 8 hours post-dose	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.
Area Under the Curve of Drug Concentration versus Time (AUC[0-t])	Within 30 minutes prior to dosing (baseline) to 8 hours post-dose	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.
Peak Plasma Concentration (C[max])	Within 30 minutes prior to dosing (baseline) to 8 hours post-dose	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.
Time to Reach Peak Plasma Concentration (t[max])	Within 30 minutes prior to dosing (baseline) to 8 hours post-dose	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.