TMC125-C227: A Phase II Randomized, Active-Controlled, Open Label Trial to Investigate the Efficacy and Tolerability of TMC125 in HIV-1 Infected Subjects, Who Are PI-Naive and With Documented Genotypic Evidence of NNRTI Resistance From Previous NNRTI Use

HIV Infection Clinical Trial

Official title:

A Phase II, Randomized, Active Controlled, Open Label Trial to Investigate the Efficacy and Tolerability of TMC125 in HIV-1 Infected Subjects, Who Are PI-na�ve and With Documented Genotypic Evidence of NNRTI Resistance From Previous NNRTI Use.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00225303
• Other study ID #: CR006730
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: May 18, 2011
• Start date: March 2005
• Est. completion date: June 2006

Study information

• Verified date: October 2010
• Source: Tibotec Pharmaceuticals, Ireland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Ireland: Irish Agriculture and Food Development Authority
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determinate the effectiveness, safety and tolerability (how well the body accepts the drug) of an investigational Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) called TMC125.

Description:

Patients who have previously received a first HIV NNRTI containing regimen or who have received an NNRTI containing treatment for prevention of mother to child transmission (MTCT), and who have never used a protease inhibitor (PI) may be eligible to participate. TMC125 (at 800 mg b.i.d. of the old formulation and after the formulation switch, 200 mg b.i.d. of the new formulation) will be studied versus an active control (investigator selected PI). All patients will receive an underlying therapy containing 2 investigator selected NRTIs. 300 patients will be enrolled in Argentina, Brazil, Mexico, Peru, Chile, Costa Rica, Russia, South-Africa, Spain, Thailand, UK, USA, Thailand, India and Malaysia. The duration of the study is 48 weeks with an optional extension for patients in the TMC125 treatment group until virologic failure or commercial availability of the drug. TMC125 at 800mg twice daily of the old formulation; after the formulation switch, TMC125 at 200mg twice daily of the new formulation. The initial duration is 48 weeks with an optional extension for patients in the TMC125 treatment group until virologic failure or commercially availability.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female, age 18 years or older

• Documented HIV-1 infection

• Stable NNRTI-containing ART (minimum 12 weeks) at screening OR treatment interruption (minimum 4 weeks) at screening OR having received an NNRTI alone or in combination with other ARVs for prevention of MTCT

• Plasma viral load at screening above 1000 HIV-1 RNA copies/ml

• Prior NNRTI-experience with documented genotypic evidence of resistance to currently available NNRTIs (defined as at least one NNRTI-associated mutation per IAS-USA Drug resistance Mutation guidelines)

• Sensitive to the 2 NRTIs to be used as underlaying ART

• Subject has given informed consent

Exclusion Criteria:

• Previous treatment with Protease Inhibitors

• 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 use which, in the investigator's opinion, would compromise the subject's safety or compliance to the study protocol procedures

• Acute Hepatitis A, B or C or chronic hepatitis B or C with elevated LFTs of > 3 times ULN

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

Drug:
• TMC125

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Tibotec Pharmaceuticals, Ireland

References & Publications (1)

Ruxrungtham K, Pedro RJ, Latiff GH, Conradie F, Domingo P, Lupo S, Pumpradit W, Vingerhoets JH, Peeters M, Peeters I, Kakuda TN, De Smedt G, Woodfall B; TMC125-C227 study group. Impact of reverse transcriptase resistance on the efficacy of TMC125 (etravir — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate antiviral activity of TMC125 800mg twice daily and after the formulation switch, 200mg twice daily as part of an ART containing 2 NRTIs, by evaluating the proportion of subjects with plasma HIV-1 RNA levels < 50 copies/mL at 24 weeks.
Secondary	Evaluate: Antiviral activity, safety, tolerability and immunologic changes over treatment period with TMC125; Changes in viral genotype and drug susceptibility during trial; Efficacy, safety and tolerability of TMC125 compared with active control group.

External Links

•   A Phase II, randomized, active controlled, open label trial to investigate the efficacy and tolerability of TMC125 in HIV-1 infected subjects, who are PI-na?ve and with documented genotypic evidence of NNRTI resistance from previous NNRTI use.