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

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ClinicalTrials.gov Identifier: NCT00862823
Recruitment Status : Completed
First Posted : March 17, 2009
Results First Posted : September 14, 2012
Last Update Posted : September 14, 2012
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Jennifer King, University of Alabama at Birmingham

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.


Condition or disease Intervention/treatment Phase
Healthy Drug: tenofovir, emtricitabine and efavirenz fixed dose tablet Drug: tenofovir, emtricitabine and efavirenz tablet added to solution Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Official Title: The Stability and Bioequivalence of Tenofovir, Emtricitabine and Efavirenz (Atripla) in an Extemporaneously Prepared Oral Liquid Formulation Compared With the Commercially Available Tablet Formulation
Study Start Date : February 2009
Actual Primary Completion Date : February 2010
Actual Study Completion Date : May 2010

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Atripla Tablet
Drug exposure after administration of Atripla Tablet
Drug: tenofovir, emtricitabine and efavirenz fixed dose tablet
Atripla contains 300mg of tenofovir, 200mg of emtricitabine and 600mg of efavirenz

Experimental: Atripla Liquid
Drug exposure after administration of an extemporaneously prepared liquid formulation of Atripla
Drug: tenofovir, emtricitabine and efavirenz tablet added to solution
Atripla contains 300mg of tenofovir, 200mg of emtricitabine and 600mg of efavirenz




Primary Outcome Measures :
  1. Area Under the Concentration Time Curve for Tenofovir, Emtricitabine and Efavirenz [ Time Frame: 17 days ]
    The area under the concentration time curve for tenofovir, emtricitabine and efavirenz

  2. Maximum Concentration for Tenofovir, Emtricitabine and Efavirenz [ Time Frame: 17 days ]
    The maximum concentration for tenofovir, emtricitabine and efavirenz



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00862823


Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
Bristol-Myers Squibb
Investigators
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Principal Investigator: Jennifer R King, PharmD University of Alabama at Birmingham
Publications of Results:
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Responsible Party: Jennifer King, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00862823    
Other Study ID Numbers: F081030003
First Posted: March 17, 2009    Key Record Dates
Results First Posted: September 14, 2012
Last Update Posted: September 14, 2012
Last Verified: June 2012
Keywords provided by Jennifer King, University of Alabama at Birmingham:
Healthy Volunteers
Additional relevant MeSH terms:
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Tenofovir
Emtricitabine
Efavirenz
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers