Triomune Bioequivalence With Innovators - Full Text View

Purpose

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.

Condition	Intervention	Phase
HIV/AIDS	Drug: Triomune Drug: Zerit/Epivir/Viramune	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Bio-equivalence Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Steady State Bioequivalence of Generic and Innovator Formulations of Stavudine, Lamivudine, and Nevirapine in HIV-infected Ugandan Adults

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Stavudine Nevirapine Lamivudine

U.S. FDA Resources

Further study details as provided by Makerere University:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]


Enrollment:	20
Study Start Date:	February 2006
Study Completion Date:	March 2008
Primary Completion Date:	June 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: Stavudine Lamivudine Nevirapine
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: Stavudine Lamivudine Nevirapine

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


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01025830

Locations


Uganda
Makerere University
Kampala, Uganda

Sponsors and Collaborators

Makerere University

University of California, San Francisco

Investigators


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

More Information

Publications:

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.


Responsible Party:	Jayne Tusiime, University of California, Berkeley
ClinicalTrials.gov Identifier:	NCT01025830 History of Changes
Other Study ID Numbers:	BETr
Study First Received:	April 21, 2009
Results First Received:	April 21, 2009
Last Updated:	December 31, 2009
Health Authority:	Uganda: Research Ethics Committee

Keywords provided by Makerere University:


HIV;Bioequivalence;Triomune

Additional relevant MeSH terms:


Lamivudine Nevirapine Stavudine Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action	Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Anti-HIV Agents Cytochrome P-450 CYP3A Inducers Cytochrome P-450 Enzyme Inducers Antimetabolites

ClinicalTrials.gov processed this record on September 26, 2016