Triomune Bioequivalence With Innovators

December 31, 2009 updated by: Makerere University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Uganda
      • Kampala, Uganda
        • Makerere University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under the Concentration-Time Curve(AUC)
Time Frame: 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
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
Time Frame: 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
Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Makerere University

Collaborators

University of California, San Francisco

Investigators

  • Principal Investigator: Jayne Tusiime, B Pharm, MSc, Makerere University
  • Study Chair: David R Bangsberg, MD,MPH, Harvard University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2006

Primary Completion (Actual)

June 1, 2006

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

April 21, 2009

First Submitted That Met QC Criteria

November 3, 2009

First Posted (Estimate)

December 4, 2009

Study Record Updates

Last Update Posted (Estimate)

January 5, 2010

Last Update Submitted That Met QC Criteria

December 31, 2009

Last Verified

December 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BETr

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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