Clinical trial NCT00071097: TMC114-C202: A Study of Safety, Efficacy, and Tolerability of TMC114 and Low Dose Ritonavir in HIV-1 Infected Patients
Official title: A Phase II Randomized, Controlled, Partially Blinded Trial to Investigate Dose Response of TMC114/RTV in 3-class-experienced HIV-1 Infected Patients, Followed by an Open-label Period on the Recommended Dose of TMC114/RTV.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV
TMC114
Ritonavir
Tolerability
Safety and efficacy
TMC114-C211
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2003-10-15
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
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 to determine the effectiveness, safety, and tolerability (how well the body stands the drug) of an investigational protease inhibitor (PI) called TMC114 given with low dose ritonavir.

Detailed description: A phase II randomized, controlled, partially blinded, trial to investigate dose response of TMC114/RTV in HIV-1 infected patients who have previously received all three licensed classes of HIV antiviral drugs (known as nucleoside reverse transcriptase inhibitors (NRTI), nonnucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI)), and who are on a stable PI-containing regimen not including an NNRTI may be eligible to participate. Four doses of TMC-114/ritonavir will be studied. 300 patients in the United States and Puerto Rico will participate. The duration of the study is 96 weeks. Randomize to one of 4 treatment groups (TMC114/RTV: 400/100 mg qd; 800/100mg qd; 400/100mg bid; 600/100 bid) or control arm for 24 to 48 wks. Optimal dose (TMC114/RTV 600/100mg bid) open label portion of the study. The trial was extended to include 144Wks of treatment.

Eligibility criteria: Inclusion Criteria:

* Male or female, age 18 years or older
* Documented HIV-1 infection
* Stable PI regimen for at least 8 weeks prior to screening
* Plasma viral load at screening above 1000 HIV-1 RNA copies/ml
* Prior use of more than 1 NRTI for at least 3 months
* Prior use of one or more NNRTIs as part of a failing regimen
* At least 1 primary PI mutation as defined by the IAS guidelines
* Treatment with at least 1 PI for a total of at least 3 months
* Patient has given informed consent

Exclusion Criteria:

* Presence of any currently active AIDS defining illness except stable cutaneous Kaposi's Sarcoma and Wasting syndrome due to HIV infection
* Current or past history of alcohol and/or drug abuse which, in the investigator's opinion, would compromise the subject's safety or compliance to the study protocol procedures
* NNRTI as part of therapy at screening
* Patients on a treatment interruption at screening
* Patients for whom an investigational antiretroviral therapy is part of the regimen at screening or the use of any non-antiretroviral investigational agents 90 days prior to screening
* Hepatitis A, B, or C.

Primary outcomes:
measure: To evaluate the dose-response relationship of antiviral activity of the TMC114/RTV dose regimens at 24 Wks in order to determine the optimal dose.
timeFrame: 24 weeks
Secondary outcomes:
measure: To evaluate safety and tolerability over 24 to 144Wks; The durability of the antiviral activity; The effect of functional monotherapy with TMC114 over 2 weeks in different doses; and The dose-response by comparing the different TMC114/RTV dosages.
timeFrame: 144 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Beverly Hills
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Oakland
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: West Hollywood
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Altamonte Springs
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Ft Lauderdale
country: United States
state: Florida
city: Miami Beach
country: United States
state: Florida
city: Miami
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: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Springfield
country: United States
state: Massachusetts
city: Camden
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: New York
country: United States
state: New York
city: Huntersville
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Hershey
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Galveston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Hampton
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
Study officials:
affiliation: Tibotec Pharmaceutical Limited
name: Tibotec Pharmaceuticals Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Clotet B, Bellos N, Molina JM, Cooper D, Goffard JC, Lazzarin A, Wohrmann A, Katlama C, Wilkin T, Haubrich R, Cohen C, Farthing C, Jayaweera D, Markowitz M, Ruane P, Spinosa-Guzman S, Lefebvre E; POWER 1 and 2 study groups. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. Lancet. 2007 Apr 7;369(9568):1169-78. doi: 10.1016/S0140-6736(07)60497-8.
citation: De Meyer SM, Spinosa-Guzman S, Vangeneugden TJ, de Bethune MP, Miralles GD. Efficacy of once-daily darunavir/ritonavir 800/100 mg in HIV-infected, treatment-experienced patients with no baseline resistance-associated mutations to darunavir. J Acquir Immune Defic Syndr. 2008 Oct 1;49(2):179-82. doi: 10.1097/QAI.0b013e318183a959.