Steady State Bioequivalence of Generic and Innovator Formulations of Stavudine, Lamivudine, and Nevirapine in HIV-infected Ugandan Adults

Triomune Bioequivalence With Innovators

Sponsors

Lead sponsor: Makerere University

Collaborator: University of California, San Francisco

Source Makerere University
Brief Summary

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.

Detailed Description

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.

Overall Status Completed
Start Date February 2006
Completion Date March 2008
Primary Completion Date June 2006
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Area Under the Concentration-Time Curve(AUC) Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing
Secondary Outcome
Measure Time Frame
Maximum Plasma Concentration of Drug Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing
Enrollment 20
Condition
Intervention

Intervention type: Drug

Intervention name: Triomune

Description: Stavudine (40mg) Lamivudine (150mg) Nevirapine (200mg)All twice a day

Arm group label: Generic

Intervention type: Drug

Intervention name: Zerit/Epivir/Viramune

Description: Stavudine (40mg) Lamivudine (150mg) and Nevirapine (200mg) All taken twice daily.

Arm group label: Brand

Eligibility

Criteria:

Inclusion Criteria:

1. HIV-infected men and non-pregnant women;

2. On Triomune for at least 4 weeks;

3. 18 years or greater;

4. Residing within 15km of Kampala city center

Exclusion Criteria:

1. Unable to sign or understand informed consent

2. Concurrent medication known to interact with any of the components of Triomune

3. Patients with active TB, malabsorption, nausea, emesis, abdominal discomfort, chronic diarrhoea, documented active clinically relevant hepatitis;

4. Patients expected to change their drug regimen or dosage during the study

5. Those planning to move out of Kampala in the next two months;

6. Hemoglobin <7.0 mmol/l (men) or <6.5 mmol/l (women);

7. Alanine aminotransferase or aspartate aminotransferase >5 times the upper limit of normal;

8. Serum creatinine > 1.5 times the upper limit of normal

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Location
facility Makerere University
Location Countries

Uganda

Verification Date

December 2009

Responsible Party

Name title: Jayne Tusiime

Organization: University of California, Berkeley

Keywords
Has Expanded Access No
Number Of Arms 2
Arm Group

Arm group label: Generic

Arm group type: Experimental

Description: generic fixed dose combination of Stavudine, Lamivudine and Nevirapine (Triomune)

Arm group label: Brand

Arm group type: Active Comparator

Description: 3 separate single pills of Zerit (Stavudine)Epivir (Lamivudine) Viramune (Nevirapine)

Study Design Info

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov