TMC125-C206: A Phase III Study to Investigate the Efficacy, Tolerability and Safety of TMC125 as Part of an Antiretroviral Regimen, Including TMC114/Ritonavir and an Investigator-selected Optimized Background, in HIV-1 Infected Patients With Limited to no Treatment Options.

NCT ID: NCT00254046

Last Updated: 2014-06-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

616 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-11-30

Study Completion Date

2008-07-31

Brief Summary

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The purpose of this study is research with the goal of evaluating the effect of TMC125 (a non-nucleoside reverse transcriptase inhibitor) on slowing down the growth of the HIV virus. The study will also investigate whether this new medication is well tolerated, and to further confirm that the medication is safe to be used.

Detailed Description

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This is a Phase III, randomized, double-blind, placebo-controlled trial to evaluate the long-term efficacy, tolerability, and safety of TMC125 as part of an antiretroviral therapy (ART) regimen containing TMC114/ritonavir (RTV) and an investigator-selected optimized background (OBR) in treatment-experienced HIV-1 infected patients. TMC125 is a non-nucleoside reverse transcriptase inhibitor (NNRTI). TMC114 is a protease inhibitor (PI). In this trial, TMC114 will be given with a low dose of ritonavir (RTV), a protease inhibitor commonly used with other, full dose protease inhibitors to improve activity. Additional assessment to be evaluated in this trial include: changes in the HIV-1 genotype, drug susceptibility, and the population pharmacokinetics of TMC125. A pharmacokinetic substudy will be performed at selected sites. Health-related quality of life will be assessed for patients receiving an antiretroviral therapy containing either TMC125 or placebo. Safety and tolerability will be documented throughout the trial. Six hundred HIV-1 infected patients on a stable but virologically failing regimen will be included in the trial. Patients should have at least 1 documented non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutation (either at screening or from historical genotype reports), an HIV-1 plasma viral load \> 5000 RNA copies/mL at screening, and at least 3 documented primary protease inhibitor (PI) mutations. Patients will be randomized in a 1:1 ratio to either TMC125 (200 mg twice daily) or to matching placebo; both in combination with TMC114/RTV (600/100 mg twice daily) and an investigator selected OBR of at least 2 antiretrovirals (ARVs), consisting of nucleoside reverse transcriptase inhibitor(s) (NRTI\[s\]) with or without enfuvirtide. The trial will involve a screening period of up to 6 weeks, a 48-week treatment period, and a 4-week follow-up period. Patients will take 200 mg oral doses of TMC125 tablets or placebo tablets; twice daily (administered as 2 tablets twice daily, with food) in combination with 600 mg oral doses of TMC114 tablets and 100 mg oral doses of ritonavir (administered as 2 tablets of TMC114 and 1 capsule of ritonavir twice daily, with food). The treatment period is 48 weeks.

Conditions

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HIV

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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002

Placebo 2 tablets b.i.d.96 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

2 tablets b.i.d.96 weeks

001

TMC125 2 X100 mg tablets b.i.d.96 weeks

Group Type ACTIVE_COMPARATOR

TMC125

Intervention Type DRUG

2 X100 mg tablets b.i.d.96 weeks

Interventions

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TMC125

2 X100 mg tablets b.i.d.96 weeks

Intervention Type DRUG

Placebo

2 tablets b.i.d.96 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patient has 3 or more primary protease inhibitor mutations
* documented genotypic evidence of resistance to currently available NNRTIs by having at least 1 NNRTI (non-nucleoside reverse transcriptase inhibitors) resistance-associated mutation
* on a stable antiretroviral therapy for at least 8 weeks
* plasma viral load at screening visit \> 5000 HIV-1 RNA copies/mL.

Exclusion Criteria

* Active AIDS defining illnesses (except for stable, cutaneous Kaposi's Sarcoma or wasting syndrome)
* Any grade 3 or grade 4 toxicity according to the DAIDS grading scale
* Use of disallowed concurrent therapy
* Any active clinically significant disease
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tibotec Pharmaceuticals, Ireland

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tibotec Pharmaceuticals Clinical Trial

Role: STUDY_DIRECTOR

Tibotec Pharmaceutical Limited

Locations

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Little Rock, Arkansas, United States

Site Status

Beverly Hills, California, United States

Site Status

Los Angeles, California, United States

Site Status

San Diego, California, United States

Site Status

San Francisco, California, United States

Site Status

New Haven, Connecticut, United States

Site Status

Washington D.C., District of Columbia, United States

Site Status

Fort Lauderdale, Florida, United States

Site Status

Miami, Florida, United States

Site Status

North Miami Beach, Florida, United States

Site Status

Pensacola, Florida, United States

Site Status

Safety Harbor, Florida, United States

Site Status

Tampa, Florida, United States

Site Status

Vero Beach, Florida, United States

Site Status

Atlanta, Georgia, United States

Site Status

Macon, Georgia, United States

Site Status

Wichita, Kansas, United States

Site Status

Boston, Massachusetts, United States

Site Status

Newark, New Jersey, United States

Site Status

Santa Fe, New Mexico, United States

Site Status

New York, New York, United States

Site Status

The Bronx, New York, United States

Site Status

Huntersville, North Carolina, United States

Site Status

Winston-Salem, North Carolina, United States

Site Status

Portland, Oregon, United States

Site Status

Philadelphia, Pennsylvania, United States

Site Status

Austin, Texas, United States

Site Status

Dallas, Texas, United States

Site Status

Galveston, Texas, United States

Site Status

Houston, Texas, United States

Site Status

Longview, Texas, United States

Site Status

Annandale, Virginia, United States

Site Status

Buenos Aires, , Argentina

Site Status

Córdoba, , Argentina

Site Status

Neuquén, , Argentina

Site Status

San Juan Bautista, , Argentina

Site Status

Curitiba, , Brazil

Site Status

Rio de Janeiro, , Brazil

Site Status

Salvador, , Brazil

Site Status

São Paulo, , Brazil

Site Status

Providencia, , Chile

Site Status

Santiago, , Chile

Site Status

San José, , Costa Rica

Site Status

Bordeaux, , France

Site Status

Lyon, , France

Site Status

Marseille, , France

Site Status

Paris, , France

Site Status

Guadalajara, , Mexico

Site Status

Mex Ctity, , Mexico

Site Status

Mexico City, , Mexico

Site Status

Panama City, , Panama

Site Status

San Juan, , Puerto Rico

Site Status

San Juan Pr, , Puerto Rico

Site Status

Bangkok, , Thailand

Site Status

Khon Kaen, , Thailand

Site Status

Countries

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United States Argentina Brazil Chile Costa Rica France Mexico Panama Puerto Rico Thailand

References

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Katlama C, Haubrich R, Lalezari J, Lazzarin A, Madruga JV, Molina JM, Schechter M, Peeters M, Picchio G, Vingerhoets J, Woodfall B, De Smedt G; DUET-1, DUET-2 study groups. Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials. AIDS. 2009 Nov 13;23(17):2289-300. doi: 10.1097/QAD.0b013e3283316a5e.

Reference Type RESULT
PMID: 19710593 (View on PubMed)

Kakuda TN, Wade JR, Snoeck E, Vis P, Scholler-Gyure M, Peeters MP, Corbett C, Nijs S, Vingerhoets J, Leopold L, De Smedt G, Woodfall BJ, Hoetelmans RM. Pharmacokinetics and pharmacodynamics of the non-nucleoside reverse-transcriptase inhibitor etravirine in treatment-experienced HIV-1-infected patients. Clin Pharmacol Ther. 2010 Nov;88(5):695-703. doi: 10.1038/clpt.2010.181. Epub 2010 Sep 29.

Reference Type DERIVED
PMID: 20881958 (View on PubMed)

Clotet B, Clumeck N, Katlama C, Nijs S, Witek J. Safety of etravirine in HIV-1/hepatitis B and/or C virus co-infected patients: pooled 96 week results from the Phase III DUET trials. J Antimicrob Chemother. 2010 Nov;65(11):2450-4. doi: 10.1093/jac/dkq332. Epub 2010 Aug 27.

Reference Type DERIVED
PMID: 20801782 (View on PubMed)

Vingerhoets J, Azijn H, Tambuyzer L, Dierynck I, De Meyer S, Rimsky L, Nijs S, De Smedt G, de Bethune MP, Picchio G. Short communication: activity of etravirine on different HIV type 1 subtypes: in vitro susceptibility in treatment-naive patients and week 48 pooled DUET study data. AIDS Res Hum Retroviruses. 2010 Jun;26(6):621-4. doi: 10.1089/aid.2009.0239.

Reference Type DERIVED
PMID: 20507207 (View on PubMed)

Madruga JV, Cahn P, Grinsztejn B, Haubrich R, Lalezari J, Mills A, Pialoux G, Wilkin T, Peeters M, Vingerhoets J, de Smedt G, Leopold L, Trefiglio R, Woodfall B; DUET-1 study group. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet. 2007 Jul 7;370(9581):29-38. doi: 10.1016/S0140-6736(07)61047-2.

Reference Type DERIVED
PMID: 17617270 (View on PubMed)

Related Links

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Other Identifiers

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TMC125-C206

Identifier Type: -

Identifier Source: secondary_id

CR002752

Identifier Type: -

Identifier Source: org_study_id

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