A Phase IIb, multi-centre, randomised, double-blind, active-controlled, trial comparing the neuropsychiatric adverse event profile of etravirine 400 mg q.d. versus efavirenz 600 mg q.d. in combination with 2 nucleoside/nucleotide reverse transcriptase inhibitors in antiretroviral therapy-naïve HIV-1 infected subjects. - SENSE

• Register: EUCTR
• Last refreshed on: 24 April 2012
• Main ID: EUCTR2008-008655-42-DK
• Date of registration: 23/02/2009
• Prospective Registration: Yes
• Primary sponsor: Janssen Cilag International
• Public title: A Phase IIb, multi-centre, randomised, double-blind, active-controlled, trial comparing the neuropsychiatric adverse event profile of etravirine 400 mg q.d. versus efavirenz 600 mg q.d. in combination with 2 nucleoside/nucleotide reverse transcriptase inhibitors in antiretroviral therapy-naïve HIV-1 infected subjects. - SENSE
• Scientific title: A Phase IIb, multi-centre, randomised, double-blind, active-controlled, trial comparing the neuropsychiatric adverse event profile of etravirine 400 mg q.d. versus efavirenz 600 mg q.d. in combination with 2 nucleoside/nucleotide reverse transcriptase inhibitors in antiretroviral therapy-naïve HIV-1 infected subjects. - SENSE
• Date of first enrolment: 31/03/2009
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-008655-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: active-controlled If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Austria, Denmark, France, Germany, Hungary, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
• Documented HIV-1 infection.
• In the judgement of the investigator, it is appropriate to initiate ARV therapy based on the subject’s medical condition and taking into account applicable guidelines for the treatment of HIV-1 infection.
• Subject 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 = 5,000 HIV-1 RNA.
• Predicted phenotypic sensitivity at screening to the currently approved NNRTIs (EFV, ETR and NVP) and to the N(t)RTIs in their background regimen.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 as described by Bennet et al.
• Known infection with HIV-2 or with HIV-1 group O.
• Subject has any currently active AIDS defining illness (Category C conditions).
• Grade 3 or 4 laboratory abnormalities (with exceptions, as per section 4).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

HIV-1 infection
MedDRA version: 9.1 Level: LLT Classification code 10020192 Term: HIV-1

Intervention(s)

Trade Name: Intelence 100mg tablets
Product Name: etravirine (ETR, TMC125)
Product Code: TMC125 (R165335) F060
Pharmaceutical Form: Tablet
INN or Proposed INN: etravirine
CAS Number: 269055-15-4
Current Sponsor code: ETR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Sustiva
Product Name: Sustiva 600 mg film-coated tablets
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: efavirenz
CAS Number: 154598-52-4
Current Sponsor code: EFV
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To evaluate and compare ETR vs EFV over 48 wks regarding
• Antiviral activity as determined by plasma viral load
• Mean worst score during the treatment period in IMP tolerability according to the CNS and total Tolerability score, as calculated from subject report on the HIV Patient Symptoms Profile
• Percentage of subjects with at least one treatment-emergent Grade 1-4 CNS or psychiatric adverse event, judged by the investigator to be at least possibly related to the study drug
• Incidence of treatment-limiting psychiatric and/or CNS adverse events
• Safety and tolerability
• Immunologic changes (as measured by CD4+ T-cell count change from Baseline, absolute and percentage)
• Adverse events of special interest, including but not limited to rash, hyperlipidaemia and lipoatrophy
• To assess the evolution of the viral genotype and phenotype
• To evaluate the population pharmacokinetics and the pharmacokinetic/pharmacodynamic relationships for efficacy and safety of ETR.

Main Objective: To compare the proportion of subjects with at least one treatment-emergent Grade 1-4 CNS or psychiatric adverse event, observed between Baseline through Week 12 and judged by the investigator to be at least possibly related to the study drug, in the ETR group versus the control group (EFV), respectively.

Primary end point(s): The primary endpoint is the proportion of subjects with at least one treatment-emergent Grade 1-4 CNS or psychiatric adverse event, observed between Baseline through Week 12, as judged by the investigator to be at least possibly drug related to the study drug, in the ETR group versus the control group (EFV).

Secondary ID(s)

TMC125VIR2038