Triomune Bioequivalence With Innovators

HIV/AIDS Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01025830
• Other study ID #: BETr
• Status: Completed
• Phase: Phase 4
• First received: April 21, 2009
• Last updated: December 31, 2009
• Start date: February 2006
• Est. completion date: March 2008

Study information

• Verified date: December 2009
• Source: Makerere University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Uganda: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 2008
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV/AIDS

Intervention

Drug:
• Triomune
Stavudine (40mg) Lamivudine (150mg) Nevirapine (200mg)All twice a day
• Zerit/Epivir/Viramune
Stavudine (40mg) Lamivudine (150mg) and Nevirapine (200mg) All taken twice daily.

Locations

Country	Name	City	State
Uganda	Makerere University	Kampala

Sponsors (2)

Lead Sponsor	Collaborator
Makerere University	University of California, San Francisco

Country where clinical trial is conducted

Uganda, 

References & Publications (1)

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/jou — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Maximum Plasma Concentration of Drug		Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing	No