Clinical trial NCT02271334: Evaluation of Pharmacokinetics and Safety of A006 in Healthy Volunteers
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
Albuterol
Lead sponsor: Amphastar Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-10-22
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Curve of Drug Concentration versus Time (AUC[0-t])
timeFrame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
measure: Peak Plasma Concentration (C[max])
timeFrame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
measure: Time to Reach Peak Plasma Concentration (t[max])
timeFrame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
measure: Plasma Albuterol Concentrations at All Time Points
timeFrame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
Secondary outcomes:
Other outcomes:
measure: Systolic Blood Pressure (SBP) at Screening
timeFrame: Within 14 days prior to Day 1 (Visit 1)
measure: Systolic Blood Pressure (SBP)
timeFrame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
measure: Diastolic Blood Pressure (DBP) at Screening
timeFrame: Within 14 days prior to Day 1 (Visit 1)
measure: Diastolic Blood Pressure (DBP)
timeFrame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
measure: Heart Rate (HR) at Screening
timeFrame: Within 14 days prior to Day 1 (Visit 1)
measure: Heart Rate (HR)
timeFrame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
measure: 12-Lead ECG QT Intervals at Screening
timeFrame: Within 14 days prior to Day 1 (Visit 1)
measure: 12-Lead ECG QT Intervals
timeFrame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
measure: 12-Lead ECG QTc Intervals at Screening
timeFrame: Within 14 days prior to Day 1 (Visit 1)
measure: 12-Lead ECG QTc Intervals
timeFrame: Within 30 minutes prior to dosing (baseline) to 8 hours post-dose
measure: Complete Blood Count (CBC) at Screening
timeFrame: Within 14 days prior to Day 1 (Visit 1)
measure: Complete Blood Count (CBC) at End-of-Study
timeFrame: 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1))
measure: Comprehensive Metabolic Panel (CMP) at Screening
timeFrame: Within 14 days prior to Day 1 (Visit 1)
measure: Comprehensive Metabolic Panel (CMP) at End-of-Study
timeFrame: 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1))
measure: Urinalysis at Screening
timeFrame: Within 14 days prior to Day 1 (Visit 1)
measure: Urinalysis at End-of-Study
timeFrame: 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1))
measure: Incidents of Pregnancy at Screening
timeFrame: Within 14 days prior to Day 1 (Visit 1)
measure: Incidents of Pregnancy at End-of-Study
timeFrame: 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1))
measure: Serious Adverse Events
timeFrame: Signing of Informed Consent at Screening Visit to End-of-Study Visit, an expected average of 7 Weeks
measure: Other Adverse Events
timeFrame: Signing of Informed Consent at Screening Visit to End-of-Study Visit, an expected average of 7 Weeks
Locations:
city: Cypress
country: United States
facility: Amphastar Site 0035
state: California
Study officials:
affiliation: Amphastar Pharmeceuticals, Inc.
name: Safety Monitor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
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. doi: 10.1007/BF02456001.
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. doi: 10.1378/chest.107.3.629.