The Bioequivalence of Atripla in an Oral Liquid Formulation Compared With the Tablet Formulation in Healthy Volunteers
Condition: Healthy
Intervention: tenofovir, emtricitabine and efavirenz fixed dose tablet; tenofovir, emtricitabine and efavirenz tablet added to solution
Intervention description: Atripla contains 300mg of tenofovir, 200mg of emtricitabine and 600mg of efavirenz; Atripla contains 300mg of tenofovir, 200mg of emtricitabine and 600mg of efavirenz
Intervention MeSH terms: Tenofovir; Emtricitabine; Efavirenz
Phase: Phase 4
Study type: Interventional
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 19 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Healthy Volunteers

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.
    

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