HIV/AIDSPhase 4NCT01025830

Triomune Bioequivalence With Innovators

A Phase 4 study testing Triomune and Zerit/Epivir/Viramune in people with HIV/AIDS, run by Makerere University at 1 site in Uganda.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV/AIDS
What is being tested?: Triomune and Zerit/Epivir/Viramune
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteUganda
Study dates: Feb 2006to Mar 2008
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Uganda1 site

Makerere University
Kampala

Other trials in Uganda

About this study

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

Read the 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.

Conditions: HIV/AIDS
Being tested: Triomune, Zerit/Epivir/Viramune
Keywords: HIV;Bioequivalence;Triomune
Medical subject headings: Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TriomuneDrug
Also called Stavudine, Lamivudine, Nevirapine
Stavudine (40mg) Lamivudine (150mg) Nevirapine (200mg)All twice a day
Zerit/Epivir/ViramuneDrug
Also called Stavudine, Lamivudine, Nevirapine
Stavudine (40mg) Lamivudine (150mg) and Nevirapine (200mg) All taken twice daily.

Study groups in NCT01025830
Study group	Role	What they receive
Generic	Experimental	generic fixed dose combination of Stavudine, Lamivudine and Nevirapine (Triomune) Receives: Drug: Triomune
Brand	Active comparator	3 separate single pills of Zerit (Stavudine)Epivir (Lamivudine) Viramune (Nevirapine) Receives: Drug: Zerit/Epivir/Viramune

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (1)

Maximum Plasma Concentration of Drug
Maximum concentration of drug in plasma that was attained post dosing
Measured: Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2006Mar 2008

First posted4 Dec 2009 (estimated)
Study startFeb 2006
Primary completionJun 2006
Study completionMar 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIV/AIDSStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01025830
Sponsor's protocol ID: BETr
Status last verified: Dec 2009
First submitted: 21 Apr 2009
Last updated: 5 Jan 2010
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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.
PubMed 19096711

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
RecruitingEarly Phase 1
A Study of Daratumumab and Dose-Adjusted EPOCH in Plasmablastic Lymphoma
Plasmablastic Lymphoma, Ann Arbor Stage I Diffuse Large B-Cell Lymphoma
Active, not recruiting
Suubi4PrEP: Improving PrEP Access and Adherence Among Adolescent Girls and Young Women in Uganda
HIV Prevention
Not yet recruiting
Bwelela Easy Study
HIV, HIV - Human Immunodeficiency Virus
RecruitingPhase 1
AMC 120, Glofitamab Plus Chemoimmunotherapy in Newly Diagnosed HIV-Associated Large B-Cell Lymphoma (The "Glofit-RCHOP Study")
AIDS-Related Diffuse Large B-cell Lymphoma, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified

All HIV/AIDS trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Jan 2010. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Steady State Bioequivalence of Generic and Innovator Formulations of Stavudine, Lamivudine, and Nevirapine in HIV-infected Ugandan Adults
ClinicalTrials.gov ID: NCT01025830
Acronym / sponsor ID: BETr
Conditions: HIV/AIDS
Keywords: HIV;Bioequivalence;Triomune
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: Makerere UniversityUniversity, hospital or other
Collaborators: University of California, San Francisco
Study start: Feb 2006
Primary completion: Jun 2006 (actual)
Study completion: Mar 2008 (actual)
First posted: 4 Dec 2009 (estimated)
Results: Posted 4 Dec 2009

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Generic	Experimental	Drug: Triomunegeneric fixed dose combination of Stavudine, Lamivudine and Nevirapine (Triomune)
Brand	Active comparator	Drug: Zerit/Epivir/Viramune3 separate single pills of Zerit (Stavudine)Epivir (Lamivudine) Viramune (Nevirapine)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (8 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TriomuneAlso: Stavudine, Lamivudine, NevirapineStavudine (40mg) Lamivudine (150mg) Nevirapine (200mg)All twice a day	Drug	Generic
Zerit/Epivir/ViramuneAlso: Stavudine, Lamivudine, NevirapineStavudine (40mg) Lamivudine (150mg) and Nevirapine (200mg) All taken twice daily.	Drug	Brand

Primary outcome

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

1 secondary outcome

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

Results and safety

Results posted to the registry on 4 Dec 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Generic (Triomune) to Brand (Zerit/Epivir/Viramune)	8	8
Brand (Zerit/Epivir/Viramune) to Generic (Triomune)	12	12

Primary outcome: 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. Geometric mean (Standard Deviation). Unit: hour*milligram/liter

Measure	Generic Stavudine n = 7	Brand Stavudine n = 11	Generic Nevirapine n = 7	Brand Nevirapine n = 11	Generic Lamivudine n = 7	Brand Lamivudine n = 11
Value	3.6 (2.4)	3.4 (3.9)	85.8 (35.2)	79.2 (45.7)	5.2 (2.5)	6.4 (4.9)

Generic Stavudine vs Brand Stavudine: Geometric Mean Ratio: 1.1 (90% CI 0.87 to 1.38), Non-compartmental model
Generic Nevirapine vs Brand Nevirapine: Geometric Mean Ratio: 1.1 (90% CI 0.95 to 1.31), Non-compartmental model
Generic Lamivudine vs Brand Lamivudine: Geometric Mean Ratio: 0.8 (90% CI 0.65 to 0.99), Non-compartmental model

Population analysed: Analyzed population consists only of participants who had sufficient plasma samples for analysis.Intent to treat analysis was used. Separate analyses provided for each drug. Results of such a study are not combined.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Patients were in the study for 60 days and this is the period over which they were monitored for any adverse events.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Entire Study Population	0 of 20 (0%)	0 of 20 (0%)	Not reported
Generic to Brand	0 of 8 (0%)	0 of 8 (0%)	Not reported
Brand to Generic	0 of 12 (0%)	0 of 12 (0%)	Not reported

Limitations and caveats (from the sponsor): Stavudine (40mg) was used whereas currently it is Stavudine(30mg) that is recommended for usage. So our results may not be applicable to patients on Stavudine 30mg.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2010.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 19096711Byakika-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.

Related trials for HIV/AIDS

RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
RecruitingEarly Phase 1
A Study of Daratumumab and Dose-Adjusted EPOCH in Plasmablastic Lymphoma
Plasmablastic Lymphoma, Ann Arbor Stage I Diffuse Large B-Cell Lymphoma
Active, not recruiting
Suubi4PrEP: Improving PrEP Access and Adherence Among Adolescent Girls and Young Women in Uganda
HIV Prevention
Not yet recruiting
Bwelela Easy Study
HIV, HIV - Human Immunodeficiency Virus
RecruitingPhase 1
AMC 120, Glofitamab Plus Chemoimmunotherapy in Newly Diagnosed HIV-Associated Large B-Cell Lymphoma (The "Glofit-RCHOP Study")
AIDS-Related Diffuse Large B-cell Lymphoma, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jayne Tusiime, B Pharm, MSc principal investigator

Makerere University

David R Bangsberg, MD,MPH study chair

Harvard University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Triomune and Zerit/Epivir/Viramune in people with HIV/AIDS, run by Makerere University at 1 site in Uganda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jan 2010. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Dec 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01025830, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2010.