Triomune Bioequivalence With Innovators

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HIV/AIDS

Intervention / Treatment
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* Drug: Triomune
* Drug: Zerit/Epivir/Viramune


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-infected men and non-pregnant women; On Triomune for at least 4 weeks; 18 years or greater; Residing within 15km of Kampala city center Exclusion Criteria: Unable to sign or understand informed consent Concurrent medication known to interact with any of the components of Triomune Patients with active TB, malabsorption, nausea, emesis, abdominal discomfort, chronic diarrhoea, documented active clinically relevant hepatitis; Patients expected to change their drug regimen or dosage during the study Those planning to move out of Kampala in the next two months; Hemoglobin <7.0 mmol/l (men) or <6.5 mmol/l (women); Alanine aminotransferase or aspartate aminotransferase >5 times the upper limit of normal; Serum creatinine > 1.5 times the upper limit of normal

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Generic<br>generic fixed dose combination of Stavudine, Lamivudine and Nevirapine (Triomune) | Drug: Triomune<br>* Stavudine (40mg) Lamivudine (150mg) Nevirapine (200mg)All twice a day<br>* Other names: Nevirapine;|
| Active Comparator: Brand<br>3 separate single pills of Zerit (Stavudine)Epivir (Lamivudine) Viramune (Nevirapine) | Drug: Zerit/Epivir/Viramune<br>* Stavudine (40mg) Lamivudine (150mg) and Nevirapine (200mg) All taken twice daily.<br>* Other names: Nevirapine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-Time Curve(AUC) | Mean Area Under the Plasma Concentration-Time Curve for each drug, log transformed | Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV;Bioequivalence;Triomune