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

NCT00862823 | Completed Phase 4 Results

• 1 other identifier: F081030003
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Area Under the Concentration Time Curve for Tenofovir, Emtricitabine and Efavirenz

  The area under the concentration time curve for tenofovir, emtricitabine and efavirenz

  17 days

• Maximum Concentration for Tenofovir, Emtricitabine and Efavirenz

  The maximum concentration for tenofovir, emtricitabine and efavirenz

  17 days

Study Arms (2)

Atripla Tablet

ACTIVE COMPARATOR

Drug exposure after administration of Atripla Tablet

Drug: tenofovir, emtricitabine and efavirenz fixed dose tablet

Atripla Liquid

EXPERIMENTAL

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

Drug: tenofovir, emtricitabine and efavirenz tablet added to solution

Interventions

tenofovir, emtricitabine and efavirenz fixed dose tablet DRUG

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

Atripla Tablet

tenofovir, emtricitabine and efavirenz tablet added to solution DRUG

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

Atripla Liquid

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (1)

• 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.

  PMID: 22046602 RESULT

MeSH Terms

Interventions

Tenofovir; Emtricitabine; efavirenz; Tablets

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

Efavirenz exposure was highly variable and relative bioequivalence for efavirenz may have been more appropriately assessed with a larger sample size.

Results Point of Contact

• Title: Jennifer King
• Organization: University of Alabama at Birmingham

jenking@uab.edu

205-934-2696

Study Officials

• Jennifer R King, PharmD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 13, 2009
• First Posted: March 17, 2009
• Study Start: February 1, 2009
• Primary Completion: February 1, 2010
• Study Completion: May 1, 2010
• Last Updated: September 14, 2012
• Results First Posted: September 14, 2012

Record last verified: 2012-06

Locations

US (1)