The Bioequivalence of Atripla in an Oral Liquid Formulation Compared With the Tablet Formulation in Healthy Volunteers
Information source: University of Alabama at Birmingham
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: tenofovir, emtricitabine and efavirenz fixed dose tablet (Drug); tenofovir, emtricitabine and efavirenz tablet added to solution (Drug)
Phase: Phase 4
Sponsored by: University of Alabama at Birmingham
Official(s) and/or principal investigator(s):
Jennifer R King, PharmD, Principal Investigator, Affiliation: University of Alabama at Birmingham
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
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 design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label
Area Under the Concentration Time Curve for Tenofovir, Emtricitabine and Efavirenz
Maximum Concentration for Tenofovir, Emtricitabine and Efavirenz
Minimum age: 19 Years.
Maximum age: 65 Years.
- 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.
- 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
- 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
Locations and Contacts
University of Alabama at Birmingham, Birmingham, Alabama 35294, United States
Starting date: February 2009
Last updated: August 16, 2012