Evaluation of Pharmacokinetics and Safety of A006 in Healthy Volunteers (A006-D)

Amphastar Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: Proventil® MDI; Drug: A006 DPI

Study type: Interventional

Funder types: Industry

Identifiers

NCT02271334

API-A006-CL-D

Details and patient eligibility

About

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.

Full 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.

Enrollment: 22 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

---

22 participants in 4 patient groups

Treatment T1

Experimental group

Description:

One inhalation of 110 mcg A006 DPI. Total 110 mcg

Treatment:

Drug: A006 DPI

Drug: A006 DPI

Treatment T2

Experimental group

Description:

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

Treatment:

Drug: A006 DPI

Drug: A006 DPI

Treatment R1

Active Comparator group

Description:

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

Treatment:

Drug: Proventil® MDI

Drug: Proventil® MDI

Treatment R2

Active Comparator group

Description:

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

Treatment:

Drug: Proventil® MDI

Drug: Proventil® MDI