Clinical trial NCT00081588: An Open Label Trial of TMC114/RTV in HIV-1 Infected, Treatment-experienced Subjects.
Official title: An Open Label Trial of TMC114/RTV in HIV-1 Infected, Treatment-experienced Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infection
Keywords: TMC114-C215
Ritonavir
HIV infections
TMC114-C202
TMC114-C213
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2004-04-19
Enrollment: 555
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of the TMC114-C215 study is to evaluate the safety and tolerability of TMC114/RTV over time. The secondary objectives are to evaluate the antiviral activity over time and to evaluate the immunological effect over time.

Detailed description: The study will continue for 144 weeks after study medication has begun. For patients failing treatment, they must have participated in the TMC114-C213 or TMC114-C202 for at least 12 weeks and meet specific virologic failure criteria. It is estimated that approximately 150 patients may meet these criteria. Major inclusion and exclusion criteria are listed below. For new patients, they must have been on prior antiretroviral therapy, including more than one nucleoside reverse transcriptase inhibitor (NRTI), one non-nucleoside reverse transcriptase inhibitor (NNRTI) and a protease inhibitor (PI). At least one primary PI mutation must be present at screening. Many of the same centers that are participating in the TMC114-C213 and TMC-114 -C202 studies are also participating in the TMC114-C215 study. All sites have the chance to recruit rollover patients into the TMC114-C215 study and some sites listed had approval to recruit new patients into the study. The recruitment of new patients for the TMC114-C215 trial has been fully enrolled. The TMC114-C202 and TMC114-C213 have completed so no more patients are enrolled in this study. Two 300mg/100mg Darunavir/Ritonavir tablets twice daily for 144 weeks.

Eligibility criteria: Inclusion Criteria:

* Previous participation in the TMC114-C202 or TMC114-C213 trials
* Significant virologic failure during participation in the above trials
* Study participation in the treatment phase of the original trial for a total of at least 12 weeks before TMC114-C215 screening
* Patient agrees to take TMC114/RTV with at least 2 other antiretrovirals (NRTIs), with or without T-20, from baseline onwards
* Patient has given informed consent

Exclusion Criteria:

* Use of disallowed concomitant therapy
* Patient with clinical or laboratory evidence of active liver disease, liver impairment/ dysfunction or cirrhosis irrespective of liver enzyme levels
* Any active or unstable medical condition that, in the investigator's opinion, would compromise the subject's safety
* Patient with laboratory abnormalities at screening as defined by ACTG grading scheme as listed in the protocol
* Patient withdrawing consent from TMC114-C202 or TMC114-C213

Primary outcomes:
measure: The primary parameter is the confirmed virologic response at Week 24 (a drop in viral load (copies/mL) of at least 1 log10 versus baseline.
timeFrame: 24 weeks
Secondary outcomes:
measure: Proportion of patients with a virologic response; with plasma HIV-1 RNA levels < 50 copies/mL; with plasma HIV-1 RNA levels < 400 copies/mL; Time to loss of virologic response over 144 week treatment period; Change in plasma viral load at all time points
timeFrame: 144 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Beverly Hills
country: United States
state: California
city: La Jolla
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 Francisco
country: United States
state: California
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: 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: 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: Cincinnati
country: United States
state: Ohio
city: Hershey
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Galveston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
city: Darlinghurst
country: Australia
city: Melbourne
country: Australia
city: Perth
country: Australia
city: Vienna
country: Austria
city: Wien
country: Austria
city: Brussels
country: Belgium
city: Brussel
country: Belgium
city: Gent
country: Belgium
city: Campinas
country: Brazil
city: Curitiba
country: Brazil
city: Rio De Janeiro
country: Brazil
city: Sao Paulo
country: Brazil
city: Calgary
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Le Kremlin Bicetre
country: France
city: Montpellier
country: France
city: Nantes
country: France
city: Paris Cedex 10
country: France
city: Paris Cedex 12
country: France
city: Paris
country: France
city: Toulon
country: France
city: Villejuif Cedex
country: France
city: Berlin
country: Germany
city: Bonn
country: Germany
city: Düsseldorf
country: Germany
city: Essen
country: Germany
city: Freiburg
country: Germany
city: Hamburg
country: Germany
city: Kÿln
country: Germany
city: Mannheim
country: Germany
city: Munich
country: Germany
city: Budapest
country: Hungary
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Barakaldo Vizcaya S/N
country: Spain
city: Barcelona N/A
country: Spain
city: Madrid
country: Spain
city: Edinburgh
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Tibotec Pharmaceutical Limited
name: Tibotec Pharmaceuticals Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Molina JM, Cohen C, Katlama C, Grinsztejn B, Timerman A, Pedro Rde J, Vangeneugden T, Miralles D, Meyer SD, Parys W, Lefebvre E; TMC114-C208 Study Group; TMC114-C215 Study Group. Safety and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced patients: 24-week results of POWER 3. J Acquir Immune Defic Syndr. 2007 Sep 1;46(1):24-31. doi: 10.1097/QAI.0b013e3181359cfb.