TMC278-TiDP6-C215: A Clinical Trial in Treatment Naive HIV-subjects Patients Comparing TMC278 to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

This study has been completed.

Sponsor:

Information provided by:

Tibotec Pharmaceuticals, Ireland

ClinicalTrials.gov Identifier:

NCT00543725

First received: October 11, 2007

Last updated: May 14, 2012

Last verified: May 2012

History of Changes

Tracking Information

First Received Date ^ICMJE

October 11, 2007

Last Updated Date

May 14, 2012

Start Date ^ICMJE

May 2008

Primary Completion Date

January 2010 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Virological Response[ITT - TLOVR,<50 Copies/mL] [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Virological response is defined as confirmed plasma viral load < 50 HIV-1 (RNA) copies/mL at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and subjects who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes subjects who were rebounder (confirmed viral load >= 50 copies/mL after being responder) or who were never suppressed (no confirmed viral load <50 copies/mL)

Original Primary Outcome Measures ^ICMJE

Result of TMC278 is comparative to efavirez (EFV) for proportion of patients with plasma VL < 50 HIV-1 RNA copies/mL (TLOVR algorithm) at week 48 (visit number 11 of 16 total study visits)

Change History

Complete list of historical versions of study NCT00543725 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Virological Response[ITT - Snapshot,<50 Copies/mL] [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

The analysis is based on the last observed viral load (VL) data within the Week 48 window. Virologic response is defined as a VL<50 copies/mL (observed case). Missing VL was considered as non-response. Virologic Failure includes subjects who had VL>=50 copies/mL in the Wk48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a VL>=50 copies/mL, and subjects who had a switch in background regimen that was not permitted by the protocol.

Original Secondary Outcome Measures ^ICMJE

Safety and tolerability evaluation, compare antiviral activity, immunologic changes, assess viral geno- and phenotype over 96 weeks. Population PK and preference based health states and adherence assessment, Optional PK and DEXAscan substudies.

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

TMC278-TiDP6-C215: A Clinical Trial in Treatment Naive HIV-subjects Patients Comparing TMC278 to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

Official Title ^ICMJE

A Phase III, Randomized, Double-blind Trial of TMC278 25mg q.d. Versus Efavirenz 600mg q.d. in Combination With a Background Regimen Containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Antiretroviral-naive HIV-1 Infected Subjects.

Brief Summary

The purpose of this trial is to compare the effectiveness, safety and tolerability of TMC278 given at a dose of 25 mg once daily versus efavirenz (EFV) at a dose of 600 mg once daily, when combined with a background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors ( investigator choice of ABC/3TC, TDF/FTC or AZT/3TC) in HIV-1 infected patients who have not yet taken any anti-HIV drugs. The following evaluations will be done: antiviral activity, immunologic changes, and viral geno-/phenotype evolution, relationship of Pharmacokinetics (PK) and PK/Pharmacodynamics and Medical resource utilization and treatment adherence.

Detailed Description

Over the past decade, anti-human immunodeficiency virus (HIV) drugs have been introduced sequentially for use in the clinic. Currently, patients are routinely being treated with 3 or 4 drug combinations including nucleoside/tide analogue reverse transcriptase inhibitors (NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and/or fusion inhibitors. New potent antiretroviral (ARV) compounds that work in people whose HIV-1 virus is resistant to available drugs are urgently needed. This is a Phase III, randomized (study medication is assigned by chance), double-blind (neither the study physician nor the patient knows the name of the study assigned medication), double-dummy, active-controlled trial to compare the effectiveness, safety, and ability to tolerate TMC278 versus efavirenz (EFV). The study will last for 104 weeks which includes a screening period of 4 weeks, a 96-week treatment period, followed by a 4 week follow-up period. Patients will be randomly assigned (like tossing a coin) to TMC278 or to efavirenz in combination with two other anti-HIV drugs of the class nucleoside/nucleotide reverse transcriptase inhibitors. The hypothesis to be provided in this study is that the investigational drug TMC278 will perform just like efavirenz (EFV) in terms of antiviral effectiveness (i.e., suppressing of the plasma viral load to a level < 50 HIV-1 RNA (ribonucleic acid) copies/mL, in ARV-naïve HIV-infected patients. During the trial, patients' health will be monitored by physical examination, interview to assess health and well being, and laboratory testing on blood and urine samples. Experimental Group: One tablet of TMC278 25 mg daily; plus efavirenz (EFV) placebo; plus 2 nucleoside/nucleotide reverse transcriptase inhibitors; Control Group: One tablet of Placebo daily that looks just like TMC278 plus EFV 600 mg daily plus 2 nucleoside/nucleotide reverse transcriptase inhibitors for 104 weeks.

Study Type ^ICMJE

Interventional

Study Phase

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

HIV Infections
HIV-1

Intervention ^ICMJE

Drug: TMC278
25 mg tablet once daily for 96 weeks
Drug: efavirenz
600 mg tablet once daily for 96 weeks

Study Arm (s)

Active Comparator: 002
efavirenz 600 mg tablet once daily for 96 weeks

Intervention: Drug: efavirenz
Experimental: 001
TMC278 25 mg tablet once daily for 96 weeks

Intervention: Drug: TMC278

Publications *

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Enrollment ^ICMJE

680

Completion Date

February 2012

Primary Completion Date

January 2010 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Patient with documented HIV-1 infection
Patient has never been treated with a therapeutic HIV vaccine or an ARV drug prior to screening
Patient's HIV-1 plasma viral load at screening is > 5,000 HIV-1 RNA copies/mL (assayed by RNA PCR standard specimen procedure)
Patient's virus is sensitive to the 2 nucleoside/nucleotide reverse transcriptase inhibitors chosen for treatment
Patient agrees not to start ART before the baseline visit
Patient is HLA-B*5701 negative in case abacavir is included in the patient's treatment regimen.

Exclusion Criteria:

Previous use of ANY ARV drug for ANY length of time
Any documented evidence of NNRTI resistance associated mutations in patient's HIV
Category C AIDS defining illness, except, Stable Kaposi Sarcoma Wasting syndrome if not progressive
Pneumocystis carinii pneumonia (PCP) that is considered not cured
Active TB
Allergy or hypersensitivity to study or background ARTs
Specific grade 3 or 4 toxicity
Kidney impairment: calculated creatinine clearance <50 ml/min

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

United States, Australia, Belgium, Brazil, Canada, Chile, China, Costa Rica, France, Germany, India, Mexico, Panama, Portugal, Puerto Rico, Russian Federation, South Africa, Spain, Thailand, United Kingdom

Administrative Information

NCT Number ^ICMJE

NCT00543725

Other Study ID Numbers ^ICMJE

CR002704, TMC278-TIDP6-C215

Has Data Monitoring Committee

Yes

Responsible Party

Compound Development Team Leader TMC278, Tibotec Pharmaceutical Limited

Study Sponsor ^ICMJE

Tibotec Pharmaceuticals, Ireland

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Tibotec Pharmaceuticals Clinical Trial

Tibotec Pharmaceutical Limited

Information Provided By

Tibotec Pharmaceuticals, Ireland

Verification Date

May 2012

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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