Triomune Bioequivalence With Innovators

Phase 4

Completed

• Conditions: HIV/AIDS
• Interventions: Drug: Zerit/Epivir/Viramune; Drug: Triomune

• Registration Number: NCT01025830
• Lead Sponsor: 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.

Study Timeline

• Study Start: 2006-02
• Primary Completion: 2006-06
• Study Completion: 2008-03
• Study First Submitted: 2009-04-21
• Results First Submitted: 2009-04-21
• Study First Submitted QC: 2009-11-03
• Results First Submitted QC: 2009-11-03
• Status Verified: 2009-12
• Study First Posted: 2009-12-04
• Results First Posted: 2009-12-04
• Last Update Submitted: 2009-12-31
• Last Update Posted: 2010-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Brand	Zerit/Epivir/Viramune	3 separate single pills of Zerit (Stavudine)Epivir (Lamivudine) Viramune (Nevirapine)
Generic	Triomune	generic fixed dose combination of Stavudine, Lamivudine and Nevirapine (Triomune)

Primary Outcome Measures

Name	Time	Method
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	Mean Area Under the Plasma Concentration-Time Curve for each drug, log transformed

Secondary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration of Drug	Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing	Maximum concentration of drug in plasma that was attained post dosing

Trial Locations

Locations (1)

Makerere University; 🇺🇬 Kampala, Uganda