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
Condition: HIV Infection; HIV; Acquired Immunodeficiency Syndrome
MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): etravirine (ETR, TMC125); efavirenz (EFV)
Intervention type(s): Drug; Drug
Intervention description(s): 400mg once daily (4x100mg tablet) + 2 NRTI + 1 EFV placebo tablet for 48 weeks; 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Intervention MeSH terms: Efavirenz; Etravirine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: HIV; Intelence; etravirine; ETR; TMC125; Sustiva; efavirenz; EFV; Non-nucleoside Reverse Transcriptase Inhibitor; NNRTI; treatment-naive