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

NCT ID: NCT00862823

Last Updated: 2012-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2010-05-31

Brief 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.

Conditions

Healthy

Keywords

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: NONE

Study Groups

Atripla Tablet

Drug exposure after administration of Atripla Tablet

Group Type: ACTIVE_COMPARATOR

tenofovir, emtricitabine and efavirenz fixed dose tablet

Intervention Type: DRUG

Atripla contains 300mg of tenofovir, 200mg of emtricitabine and 600mg of efavirenz

Atripla Liquid

Drug exposure after administration of an extemporaneously prepared liquid formulation of Atripla

Group Type: EXPERIMENTAL

tenofovir, emtricitabine and efavirenz tablet added to solution

Intervention Type: DRUG

Atripla contains 300mg of tenofovir, 200mg of emtricitabine and 600mg of efavirenz

Interventions

tenofovir, emtricitabine and efavirenz fixed dose tablet

Atripla contains 300mg of tenofovir, 200mg of emtricitabine and 600mg of efavirenz

Intervention Type: DRUG

tenofovir, emtricitabine and efavirenz tablet added to solution

Atripla contains 300mg of tenofovir, 200mg of emtricitabine and 600mg of efavirenz

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Jennifer King

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jennifer R King, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

References

King J, McCall M, Cannella A, Markiewicz MA, James A, Hood CB, Acosta EP. A randomized crossover study to determine relative bioequivalence of tenofovir, emtricitabine, and efavirenz (Atripla) fixed-dose combination tablet compared with a compounded oral liquid formulation derived from the tablet. J Acquir Immune Defic Syndr. 2011 Apr 15;56(5):e130-2. doi: 10.1097/qai.0b013e31820eefbe. No abstract available.

Reference Type: RESULT

PMID: 22046602 (View on PubMed)

Other Identifiers

F081030003

Identifier Type: -

Identifier Source: org_study_id