Triomune Bioequivalence With Innovators
The null hypothesis is that there is a difference in the the relative rate and extent of absorption into the systemic circulation of Triomune and brand-name Stavudine/Lamivudine/Nevirapine in HIV-infected Africans and the alternative hypothesis is that there is no difference in the the relative rate and extent of absorption into the systemic circulation of Triomune and brand-name Stavudine/Lamivudine/Nevirapine in HIV-infected Africans. This is a non-inferiority study.
|Study Design:||Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Steady State Bioequivalence of Generic and Innovator Formulations of Stavudine, Lamivudine, and Nevirapine in HIV-infected Ugandan Adults|
- Area Under the Concentration-Time Curve(AUC) [ Time Frame: Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing ] [ Designated as safety issue: No ]
- Maximum Plasma Concentration of Drug [ Time Frame: Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing ] [ Designated as safety issue: No ]
|Study Start Date:||February 2006|
|Study Completion Date:||March 2008|
|Primary Completion Date:||June 2006 (Final data collection date for primary outcome measure)|
generic fixed dose combination of Stavudine, Lamivudine and Nevirapine (Triomune)
Stavudine (40mg) Lamivudine (150mg) Nevirapine (200mg)All twice a day
Active Comparator: Brand
3 separate single pills of Zerit (Stavudine)Epivir (Lamivudine) Viramune (Nevirapine)
Stavudine (40mg) Lamivudine (150mg) and Nevirapine (200mg) All taken twice daily.
Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of Lamivudine, Stavudine and Nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune®) or the corresponding brand formulations (Epivir®, Zerit®, and Viramune®). An open-label, randomized, crossover study was carried out in 18 HIV-infected Ugandan subjects stabilized on Triomune-40. Subjects received Lamivudine (150 mg), Stavudine (40 mg), and Nevirapine (200 mg) in either the generic or brand formulation twice a day for 30 days, before switching to the other formulation. At the end of each treatment period, blood samples were collected over 12 h for pharmacokinetic analysis. The main outcome measures were the mean AUC0-12h and Cmax. Bioequivalence was defined as a geometric mean ratio between the generic and brand-name within the 90% confidence interval of 0.8-1.25.
|Principal Investigator:||Jayne Tusiime, B Pharm, MSc||Makerere University|
|Study Chair:||David R Bangsberg, MD,MPH||Harvard University|