The Bioequivalence of Atripla in an Oral Liquid Formulation Compared With the Tablet Formulation in Healthy Volunteers

• Status: Completed
• Trial end date: 2010-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to determine the average bioequivalence of tenofovir, emtricitabine and efavirenz in an extemporaneously prepared oral liquid formulation (test formulation) compared with the commercially available tablet formulation (reference formulation). The study is designed as an open-label, randomized, 2-period, 2-treatment, 2-sequence, single-dose intensive pharmacokinetic study conducted in healthy volunteers. Subjects will be randomized to receive the Atripla tablet (reference formulation) or the Atripla tablet crushed and mixed in OraSweet solution (test formulation) on Study Day 1. Subjects will undergo a 12-hour intensive pharmacokinetic evaluation after ingesting a single dose of either the test or reference formulation. On days 2 and 3, subjects will provide an additional pharmacokinetic sample 24 and 48 hours post dose, respectively. Subjects will complete a washout period from day 2 to day 14 during which no study drugs will be ingested. On day 14, subjects will ingest either the reference or test formulation (opposite of the formulation received on Study Day 1). All subjects will undergo another 12-hour intensive pharmacokinetic evaluation. On days 16 and 17 subjects will provide an additional pharmacokinetic sample 24 and 48 hours post dose, respectively. Adverse events and concomitant medications will be documented throughout the study.

The sample size is 16 and is based upon a 10% drop-out rate (i.e. due to lost to follow-up, treatment discontinuation, etc.). Since the investigators are expecting two subjects not to complete the study, the investigators expect 14 evaluable subjects. If the discontinuation rate is greater than 10%, the investigators will continue to enroll until the investigators get 14 evaluable subjects. The primary endpoint is to determine average bioequivalence for test and reference formulations of tenofovir, emtricitabine and efavirenz according to the FDA guidance on bioequivalence testing. The ratio of the test to reference formulation mean Cmax and AUC24 for each drug and the 90% confidence interval around each mean ratio will be determined. Average bioequivalence will be met if 90% confidence intervals around the Cmax, and AUC24 mean ratios for each drug falls within the FDA's predefined limits of 0.80 to 1.25.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Alabama at Birmingham
• Collaborator: Bristol-Myers Squibb
• Treatments: Efavirenz; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; Tenofovir

Criteria

Inclusion Criteria:

• Age ≥19 and ≤65, HIV-1 negative, Able to give consent, Non-smoking,Screening EKG within normal limits, Females of childbearing potential must have a negative pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.

Exclusion Criteria:

• Subjects receiving any prescription or over-the-counter products will be excluded from the study. Subjects using any form of recreational drugs will be excluded. Subjects who have any of the following laboratory abnormalities within 30 days of study entry will be excluded:

• SGOT (AST)/SGPT (ALT) > 3 x upper limits of normal (ULN) (Subjects with liver disease are allowed to enroll unless their AST/ALT levels are greater than three times ULN)

• Bilirubin > 2.5 x ULN

• Amylase > 2 x ULN

• Absolute Neutrophil Count < 1000 x 103/L

• Hgb < 9.0 g/dl

• Platelets <50,000 cells/mm3

• Serum Creatinine > 2.5 mg/dl