Clinical trial NCT00254046: 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.
Official title: A Phase III Randomized, Double-blinded, Placebo-controlled Trial to Investigate the Efficacy, Tolerability and Safety of TMC125 as Part of an ART Regimen, Including TMC114/RTV and an Investigator-selected OBR, in HIV-1 Infected Patients With Limited Treatment to no Treatment Options.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
Keywords: HIV
HIV-1
TMC125
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2005-11-15
Enrollment: 616
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluation of efficacy, tolerability and safety of TMC125 as part of an antiretroviral therapy containing TMC114/ritonavir and an investigator selected optimized background regimen.
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Beverly Hills
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: New Haven
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Ft Lauderdale
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: N Miami Beach
country: United States
state: Florida
city: Pensacola
country: United States
state: Florida
city: Safety Harbor
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Vero Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: Wichita
country: United States
state: Kansas
city: Boston
country: United States
state: Massachusetts
city: Newark
country: United States
state: New Jersey
city: Santa Fe
country: United States
state: New Mexico
city: Bronx
country: United States
state: New York
city: New York
country: United States
state: New York
city: Huntersville
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Galveston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Longview
country: United States
state: Texas
city: Annandale
country: United States
state: Virginia
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Florencio Varela
country: Argentina
city: Neuquen
country: Argentina
city: Curitiba
country: Brazil
city: Rio De Janeiro
country: Brazil
city: Salvador
country: Brazil
city: Sao Paulo
country: Brazil
city: Providencia
country: Chile
city: Santiago
country: Chile
city: San Jose
country: Costa Rica
city: Bordeaux Cedex
country: France
city: Bordeaux N/A
country: France
city: Lyon
country: France
city: Marseille Cedex 09
country: France
city: Paris
country: France
city: Ciudad De Mexico
country: Mexico
city: Guadalajara
country: Mexico
city: Mex Ctity
country: Mexico
city: Panama
country: Panama
city: San Juan Pr
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Bangkok
country: Thailand
city: Khon Kaen
country: Thailand
Study officials:
affiliation: Tibotec Pharmaceutical Limited
name: Tibotec Pharmaceuticals Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.