A Study With TMC125 in Human Immunodeficiency Virus (HIV) Type 1 Infected Patients, Who Were Treated With TMC125 Arm in a Sponsor-Selected TMC125 Study

An Open-Label Trial With TMC125 in HIV-1 Infected Subjects, Who Were Randomized to a TMC125 Treatment Arm in a Sponsor-Selected TMC125 Trial and Were Treated for at Least 48 Weeks

The purpose of this study is to evaluate the long-term safety and tolerability of etravirine, administered as part of an individually optimized antiretroviral therapy (ART), in human immunodeficiency virus Type 1 (HIV-1) infected participants.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus Type 1
• Intervention / Treatment: Drug: Etravirine (ETR); Drug: Nucleotide reverse transcriptase inhibitors (NRTIs); Drug: Protease inhibitors (PIs); Drug: Enfuvirtide (ENF)

Detailed Description

This is a Phase II, open-label (all people know the identity of the intervention), roll-over study (participants may go ahead and participate in another clinical study). Participants who were randomized (study medication is assigned by chance) to a etravirine (ETR) treatment arm in Phase II TMC125 feeder studies (TMC125-C203, TMC125-C209, TMC125-C223 and TMC125-C211), were treated for at least 48 weeks with etravirine, and who will derive continued benefit from etravirine therapy, as judged by the investigator, will be enrolled in this study. The final visit of the sponsor-selected Phase II ETR study will be the first (baseline) visit of this study. Approximately 300 participants will be enrolled in this study who will receive 800 mg twice daily of etravirine (formulation TF035) until the formulation 200 mg twice daily (formulation F060) is available. Once this formulation becomes available all the participants will be switched to receive F060 which will be given in combination with an investigator-selected, optimized underlying therapy (nucleotide reverse transcriptase [NRTIs] and/or allowed protease inhibitors and/or enfuvirtide). Participants will continue to receive ETR until they are no longer benefitted or this medication becomes commercially available. Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination.

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants who were previously randomized to an etravirine (ETR) treatment arm and have completed at least 48 weeks of treatment with ETR
• Participants who will be able to comply with the protocol requirements
• Participants general medical condition should not interfere with the assessments and the completion of the study

Exclusion Criteria:

• Use of disallowed concomitant therapy unless a prior exemption had been granted
• Participant with any treatment-emergent condition or exacerbation of underlying condition during original Phase II study
• Agrees to protocol-defined use of effective contraception
• Participant with a grade 3 elevation of amylase and/or lipase except for isolated grade 3 increases of amylase with lipase in normal range and no history of pancreatitis
• Participant with any grade 4 toxicity according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading table; with the exception of grade 4 elevations of triglycerides or glucose asymptomatic or under non-fasting conditions; grade 4 elevation of glucose in participants with pre-existing diabetes
• Participants with clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (International Normalized Ratio [INR] more than 1.5 or albumin less than 30g/l or bilirubin more than 2.5 x upper limit of normal)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Etravirine + 2 antiretrovirals

Drug: Etravirine (ETR); Participants will receive 800 mg of ETR (2 x 4 tablets of formulation TF035) twice daily and after the formulation switch they will receive 200 mg of ETR (2 x 2 tablets of formulation F060) twice daily until the participants benefitted from etravirine or it became comercially available.; Other Names: TMC125; Drug: Nucleotide reverse transcriptase inhibitors (NRTIs); Participants will receive 2 additonal approved antiretrovirals (ARVs) along with ETR. ARVs may be NRTIs and/or allowed protease inhibitors (PIs) and/or enfuvirtide (ENF).; Drug: Protease inhibitors (PIs); Participants will receive 2 additonal approved antiretrovirals (ARVs) along with ETR. ARVs may be NRTIs and/or allowed protease inhibitors (PIs) and/or enfuvirtide (ENF).; Drug: Enfuvirtide (ENF); Participants will receive 2 additonal approved antiretrovirals (ARVs) along with ETR. ARVs may be NRTIs and/or allowed protease inhibitors (PIs) and/or enfuvirtide (ENF).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Number of participants who reported at least 1 of the adverse events.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved Virologic Response (ie, Viral Load Less Than 50 Copies/mL) at Week 48	Number of participants who had viral load more than or equal to 50 copies/mL and less than 50 copies/mL at TMC125-C229 baseline and who achieved virologic response (ie, viral load less than 50 copies/mL) at Week 48. The last visit of the TMC125 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies) was considered to be the TMC125-C229 baseline.	Week 48
Number of Participants Who Achieved Virologic Response (ie, Viral Load Less Than 50 Copies/mL) at Week 96	Number of participants who had viral load more than or equal to 50 copies/mL and less than 50 copies/mL at TMC125-C229 baseline and who achieved virologic response (ie, viral load less than 50 copies/mL) at Week 96. The last visit of the TMC125 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies) was considered to be the TMC125-C229 baseline.	Week 96
Number of Participants Who Achieved Virologic Response (ie, Viral Load Less Than 50 Copies/mL; Less Than 400 Copies/mL; and Greater Than or Equal to 1 Log 10 Decrease From Baseline) at Week 96	Baseline considered for this outcome is the baseline in the respective TMC125-C229 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies).	Week 96
Number of Participants Who Achieved Virologic Response (ie, Viral Load Less Than 50 Copies/mL; Viral Load Less Than 400 Copies/mL; and Greater Than or Equal to 1 log10 Decrease From Baseline) at Week 192	Baseline considered for this outcome is the baseline in the respective TMC125-C229 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies).	Week 192
Median Change From TMC125-C229 Basline in Cluster of Differentiation 4 (CD4+) Cell Count at Week 48	The last visit of the TMC125 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies) was considered to be the TMC125-C229 baseline.	Week 48
Median Change From TMC125-C229 Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Week 96	The last visit of the TMC125 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies) was considered to be the TMC125-C229 baseline.	Week 96
Median Change in Cluster of Differentiation 4 (CD4+) Cell Count From Baseline in TMC125-C229 Feeder Study at Week 96	Baseline considered for this outcome is the baseline in the respective TMC125-C229 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies).	Week 96
Median Change in Cluster of Differentiation 4 (CD4+) Cell Count From Baseline in TMC125-C229 Feeder Study at Week 192	Baseline considered for this outcome is the baseline in the respective TMC125-C229 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies).	Week 192
Number of Participants With Emerging Mutation (Reverse Transcriptase Mutation)	Emerging mutations are the mutation which are not present at baseline (last visit of the TMC125 feeder study [TMC125-C203 (NCT00412646), TMC125-C223 (NCT00081978), TMC125 C211 (NCT00111280) or TMC125-C209 feeder studies]) and are present at endpoint (last available timepoint during treatment period for each individual participant).	Baseline and Endpoint (ie, the last available time point during the treatment period)

Collaborators and Investigators

• Sponsor: Tibotec Pharmaceuticals, Ireland

Publications and helpful links

Helpful Links

• TMC125-C229: TMC125 in HIV-1 Infected Subjects, Who Were Randomized to a TMC125 Treatment Arm in a Sponsor Selected TMC125 Trial and Were Treated for at Least 48 Weeks

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: August 8, 2005
• First Submitted That Met QC Criteria: August 8, 2005
• First Posted (Estimate): August 10, 2005

Study Record Updates

• Last Update Posted (Estimate): June 20, 2013
• Last Update Submitted That Met QC Criteria: June 10, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Antiretroviral therapy; Etravirine; HIV-1 infection; TMC125; Human Immunodeficiency Virus Type 1; Enfuvirtide
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Viral Protease Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Protease Inhibitors; Enfuvirtide; Reverse Transcriptase Inhibitors; Etravirine; HIV Protease Inhibitors
• Other Study ID Numbers: CR002731; TMC125-C229 (Other Identifier: Tibotec Pharmaceuticals, Ireland)