Clinical trial NCT01025830: Triomune Bioequivalence With Innovators
Official title: Steady State Bioequivalence of Generic and Innovator Formulations of Stavudine, Lamivudine, and Nevirapine in HIV-infected Ugandan Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV/AIDS
Keywords: HIV;Bioequivalence;Triomune
Lead sponsor: Makerere University
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
First posted: 2009-12-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Area Under the Concentration-Time Curve(AUC)
timeFrame: Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing
Secondary outcomes:
measure: Maximum Plasma Concentration of Drug
timeFrame: Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Makerere University
Study officials:
affiliation: Makerere University
name: Jayne Tusiime, B Pharm, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Harvard University
name: David R Bangsberg, MD,MPH
role: STUDY_CHAIR
References:
citation: Byakika-Tusiime J, Chinn LW, Oyugi JH, Obua C, Bangsberg DR, Kroetz DL. Steady state bioequivalence of generic and innovator formulations of stavudine, lamivudine, and nevirapine in HIV-infected Ugandan adults. PLoS One. 2008;3(12):e3981. doi: 10.1371/journal.pone.0003981. Epub 2008 Dec 19.