Evaluation of Pharmacokinetics and Safety of A006 in Healthy Volunteers

Study Overview
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Brief Summary
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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
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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.

Official Title
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Evaluation of Pharmacokinetics and Safety of A006 in Healthy Volunteers (A Randomized, Double- or Evaluator-blinded, Single-dose, Four-arm, Crossover Pharmacokinetics (PK) Study in Healthy Adults)

Conditions
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Asthma

Intervention / Treatment
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* Drug: A006 DPI
* Drug: A006 DPI
* Drug: Proventil® MDI
* Drug: Proventil® MDI


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment T1<br>One inhalation of 110 mcg A006 DPI. Total 110 mcg | Drug: A006 DPI<br>* Single dose 110 mcg, 1 inhalation<br>* Other names: Albuterol DPI;|
| Experimental: Treatment T2<br>One inhalation of 220 mcg A006 DPI. Total 220 mcg. | Drug: A006 DPI<br>* Single dose 220 mcg, 1 inhalation<br>* Other names: Albuterol DPI;|
| Active Comparator: Treatment R1<br>One inhalation of 90 mcg Proventil® MDI. Total 90 mcg. | Drug: Proventil® MDI<br>* Single dose 90 mcg, 1 inhalation<br>* Other names: Proventil®;|
| Active Comparator: Treatment R2<br>Two inhalations of 90 mcg Proventil® MDI. Total 180 mcg | Drug: Proventil® MDI<br>* Single dose 90 mcg, 2 inhalations<br>* Other names: Proventil®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Albuterol