A Clinical Trial Comparing the Tolerability of Etravirine to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Treatment-naive HIV-1 Infected Patients

NCT ID: NCT00903682

Last Updated: 2013-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 157 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2011-01-31

Brief Summary

The purpose of this study is to compare the neuropsychiatric adverse event profiles of etravirine 400mg once daily versus efavirenz 600mg once daily, in combination with 2 N(t)RTIs, in approximately 150 treatment-naÃ-ve HIV-1 infected patients. Safety, tolerability and efficacy of both treatment arms will be assessed throughout the study.

Detailed Description

This is a phase IIb, randomised (study medication is assigned by chance), double-blind (neither the patient nor the study physician will know to which treatment group the patient is assigned) trial to assess the neuropsychiatric adverse event profile of etravirine (ETR) 400mg once daily versus efavirenz (EFV) 600mg once daily, each in combination with an investigator-selected background of 2 other anti-HIV drugs of the class nucleoside/nucleotide reverse transcriptase inhibitors (N[t]RTIs). The combination of N[t]RTIs to be chosen by the study physician can be abacavir (ABC)/lamivudine (3TC), zidovudine (AZT)/lamivudine (3TC) or tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC). Approximately 150 Human Immuno-deficiency Virus type 1 (HIV-1) infected patients, who have never received any antiretroviral (ARV) treatment will be randomly assigned (like tossing a coin) to either the etravirine treatment group or the control group (efavirenz). The study period includes a screening period of maximum 6 weeks, a 48 week treatment period, an additional 2-8 weeks treatment until unblinding (study physician (and patient) will receive information to which treatment group the patient is assigned), followed by a 4 weeks follow-up period. The main purpose of this study is to gather further data on how many, how often, and how severe the central nervous system and psychiatric (neuropsychiatric) events are between the two treatment groups. In addition, the study will look at overall safety, tolerability and antiviral effectiveness between the two treatment groups. During the trial, patients' health will be monitored by physical examination, checking of vital signs (blood pressure / pulse), and laboratory testing on blood and urine samples. Also blood samples will be drawn to measure the antiviral effectiveness (i.e., decrease of the plasma viral load to a level <50 HIV-1 RNA (ribonucleic acid) copies/mL), immunology assessments (to assess the body's immune system) and pharmacokinetic (to measure the drug level in blood) analysis of etravirine. Patients will be asked to complete the "HIV Patient Symptoms Profile" (HIV PSP) Questionnaire at each visit, which contains questions relating to the impact on patients' current health and well-being. The study hypothesis is that the proportion of patients with at least one neuropsychiatric adverse event related to the study drug, observed between start of treatment (Baseline; BSL) through Week 12, is significantly lower in the etravirine group than in the efavirenz group. Patients will be taking blinded medication twice a day, administered orally (by mouth). Only one of the blinded doses will contain an active ingredient. Etravirine 400mg (or dummy-pills) - 4 tablets - should be taken once a day, following a meal, preferably breakfast. Efavirenz 600mg (or dummy-pill) - 1 tablet - should be administered once daily on an empty stomach, preferably at bedtime.The intake of the investigator-selected N[t]RTIs should be taken as instructed by the investigator.

Conditions

HIV Infection; HIV; Acquired Immunodeficiency Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

etravirine

etravirine (ETR TMC125) 400mg once daily (4x100mg tablet) + 2 NRTI + 1 EFV placebo tablet for 48 weeks

Group Type: EXPERIMENTAL

etravirine (ETR, TMC125)

Intervention Type: DRUG

400mg once daily (4x100mg tablet) + 2 NRTI + 1 EFV placebo tablet for 48 weeks

efavirenz

efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks

Group Type: ACTIVE_COMPARATOR

efavirenz (EFV)

Intervention Type: DRUG

600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks

Interventions

etravirine (ETR, TMC125)

400mg once daily (4x100mg tablet) + 2 NRTI + 1 EFV placebo tablet for 48 weeks

Intervention Type: DRUG

efavirenz (EFV)

600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Documented HIV-1 infection
• In the judgement of the investigator, it is appropriate to initiate ARV therapy based on the patients medical condition and taking into account applicable guidelines for the treatment of HIV-1 infection
• Patient has access to an investigator-selected ARV regimen post-study in accordance with applicable guidelines for the treatment of HIV-1 infection
• HIV-1 plasma viral load at screening >= 5000 HIV-1 RNA (copies/ml)
• Predicted phenotypic sensitivity to the currently approved NNRTIs and to the N(t)RTIs in their background regimen at screening

Exclusion Criteria

• Any previous treatment with a therapeutic HIV vaccine or use of ARVs, including use of NVP for the prevention of vertical HIV transmission
• The presence of at least one of the mutations that are specific indicators of transmitted (or primary) drug resistance
• Known infection with HIV-2 or with HIV-1 group O
• Category C AIDS defining illness, except stable Kaposi's Sarcoma, wasting syndrome if not progressive
• Pneumocystis jiroveci/carinii Pneumonia (PCP) that is considered not cured
• Specific grade 3 or 4 laboratory abnormalities

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag International NV

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen-Cilag International NV Clinical Trial

Role: STUDY_DIRECTOR

Janssen-Cilag International NV

Locations

Salzburg, , Austria

Vienna, , Austria

Aarhus, , Denmark

Odense, , Denmark

Bordeaux, , France

Lyon, , France

Nice, , France

Paris, , France

Strasbourg, , France

Berlin, , Germany

Bonn, , Germany

Cologne, , Germany

Essen, , Germany

Frankfurt, , Germany

Hamburg, , Germany

Hanover, , Germany

Budapest, , Hungary

Haifa, , Israel

Jerusalem, , Israel

Ramat Gan, , Israel

Tel Aviv, , Israel

Bucharest, , Romania

Constanța, , Romania

Moscow, , Russia

Saint Petersburg, , Russia

Barcelona, , Spain

Granada, , Spain

Madrid, , Spain

Vigo, , Spain

Bern, , Switzerland

Zurich, , Switzerland

Brighton, , United Kingdom

London, , United Kingdom

Countries

Austria; Denmark; France; Germany; Hungary; Israel; Romania; Russia; Spain; Switzerland; United Kingdom

References

Nelson M, Stellbrink HJ, Podzamczer D, Banhegyi D, Gazzard B, Hill A, van Delft Y, Vingerhoets J, Stark T, Marks S. A comparison of neuropsychiatric adverse events during 12 weeks of treatment with etravirine and efavirenz in a treatment-naive, HIV-1-infected population. AIDS. 2011 Jan 28;25(3):335-40. doi: 10.1097/QAD.0b013e3283416873.

Reference Type: RESULT

PMID: 21150563 (View on PubMed)

Gazzard B, Duvivier C, Zagler C, Castagna A, Hill A, van Delft Y, Marks S. Phase 2 double-blind, randomized trial of etravirine versus efavirenz in treatment-naive patients: 48-week results. AIDS. 2011 Nov 28;25(18):2249-58. doi: 10.1097/QAD.0b013e32834c4c06.

Reference Type: RESULT

PMID: 21881478 (View on PubMed)

Fatkenheuer G, Duvivier C, Rieger A, Durant J, Rey D, Schmidt W, Hill A, van Delft Y, Marks S; SENSE Study Team. Lipid profiles for etravirine versus efavirenz in treatment-naive patients in the randomized, double-blind SENSE trial. J Antimicrob Chemother. 2012 Mar;67(3):685-90. doi: 10.1093/jac/dkr533. Epub 2011 Dec 29.

Reference Type: DERIVED

PMID: 22210755 (View on PubMed)

Other Identifiers

TMC125VIR2038

Identifier Type: OTHER

Identifier Source: secondary_id

2008-008655-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR015751

Identifier Type: -

Identifier Source: org_study_id