- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00903682
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 (SENSE)
January 7, 2013 updated by: Janssen-Cilag International NV
A Phase IIb, Multi-centre, Randomised, Double-blind, Active-controlled Trial Comparing the Neuropsychiatric Adverse Event Profile of Etravirine 400mg qd Versus Efavirenz 600mg qd in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in ARV Therapy-naive HIV-1 Infected Subjects
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
157
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Salzburg, Austria
-
Vienna, Austria
-
Wien, Austria
-
-
-
-
-
Aarhus, Denmark
-
Odense N/A, Denmark
-
-
-
-
-
Bordeaux Cedex, France
-
Lyon, France
-
Nice, France
-
Paris, France
-
Strasbourg Cedex, France
-
-
-
-
-
Berlin, Germany
-
Bonn, Germany
-
Essen, Germany
-
Frankfurt, Germany
-
Hamburg, Germany
-
Hannover, Germany
-
Koln, Germany
-
-
-
-
-
Budapest, Hungary
-
-
-
-
-
Haifa, Israel
-
Jerusalem, Israel
-
Ramat-Gan, Israel
-
Tel-Aviv, Israel
-
-
-
-
-
Bucuresti, Romania
-
Constanta, Romania
-
-
-
-
-
Moscow, Russian Federation
-
Moscow N/A, Russian Federation
-
Saint-Petersburg, Russian Federation
-
St Petersburg, Russian Federation
-
-
-
-
-
Barcelona, Spain
-
Barcelona N/A, Spain
-
Granada, Spain
-
Madrid, Spain
-
Vigo, Spain
-
-
-
-
-
Bern, Switzerland
-
Zurich N/A, Switzerland
-
-
-
-
-
Brighton, United Kingdom
-
London, United Kingdom
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: etravirine
etravirine (ETR TMC125) 400mg once daily (4x100mg tablet) + 2 NRTI + 1 EFV placebo tablet for 48 weeks
|
400mg once daily (4x100mg tablet) + 2 NRTI + 1 EFV placebo tablet for 48 weeks
|
Active Comparator: efavirenz
efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
|
600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Patients With at Least 1 Treatment-emergent Grade 1-4 Central Nervous System or Psychiatric Adverse Event
Time Frame: between baseline and 12 weeks
|
Proportion of patients with at least 1 treatment-emergent Grade 1-4 Central Nervous System or psychiatric Adverse Event, observed between Baseline through Week 12 and judged by investigator to be at least possibly related to the study drug in ETR group versus EFV group.
All Adverse Events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events ("DAIDS AE grading table").
Grade 1-4 covers all severities.
|
between baseline and 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Antiviral Activity of ETR vs. EFV
Time Frame: between baseline and week 48
|
The proportion of patients with confirmed plasma viral load <50 copies/mL at Week 48 as assessed by Time to Loss of Virologic Response (TLOVR)
|
between baseline and week 48
|
Antiviral Activity of ETR vs. EFV
Time Frame: between baseline and week 48
|
The proportion of patients with confirmed plasma viral load <200 copies/mL at Week 48 as assessed by Time to Loss of Virologic Response (TLOVR)
|
between baseline and week 48
|
Mean Change From Baseline in Neuropsychiatric and Total Tolerabililty Score
Time Frame: between baseline and week 48
|
The HIV Patient Symptoms Profile measures the tolerability of HIV treatment from the patient's perspective, using 14 concept scales in maximum 84 questions.
The response options include a "no" or "yes" answer to "Did symptom occur?".
If "yes", there is a problem scale which ranges from 1 = "I had this symptom and it was not a problem" to 5 = "I had this symptom and it was a severe problem".
A neuropsychiatric tolerability score is composed as the sum of 21 items and ranges from 0 (best) to 105 (worse).
A total Tolerability score (ie, the sum of all items) ranges from 0 (best) to 420 (worse)
|
between baseline and week 48
|
Neuropsychiatric Adverse Events by Week 48
Time Frame: from baseline to week 48
|
The percentage of patients with at least 1 treatment emergent Grade 1 -4 neurologic or psychiatric adverse event, judged by the investigator to be at least possibly related to the study drug.
|
from baseline to week 48
|
Mean Change From Baseline in CD4+ Cell Count
Time Frame: at baseline and week 2, 6, 12, 24, 36 and 48
|
The mean change in CD4+ cell count from baseline was calculated with a last observation carried forward method; i.e. the last observed value was carried forward, irrespective of the reason for discontinuation.
|
at baseline and week 2, 6, 12, 24, 36 and 48
|
Resistance Determinations
Time Frame: at baseline and all subsequent visits until week 48 in case if virologic failure
|
The evolution of viral genotype and phenotype was assessed by the number of patients with resistance-associated mutations emerging at the endpoint.
A mutation was considered emerging if it was present at endpoint and not present at baseline or any pre-baseline assessment.
(NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; RAM = resistance-associated mutation, IAS-USA = International AIDS Society - USA)
|
at baseline and all subsequent visits until week 48 in case if virologic failure
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2009
Primary Completion (Actual)
February 1, 2010
Study Completion (Actual)
January 1, 2011
Study Registration Dates
First Submitted
May 14, 2009
First Submitted That Met QC Criteria
May 14, 2009
First Posted (Estimate)
May 18, 2009
Study Record Updates
Last Update Posted (Estimate)
January 14, 2013
Last Update Submitted That Met QC Criteria
January 7, 2013
Last Verified
January 1, 2013
More Information
Terms related to this study
Keywords
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
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors
- Etravirine
- Efavirenz
Other Study ID Numbers
- CR015751
- TMC125VIR2038 (Other Identifier: Janssen-Cilag International NV)
- 2008-008655-42 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acquired Immunodeficiency Syndrome
-
VA Eastern Colorado Health Care SystemPublic Health Grant Program, Veterans Health Administration Office of Public...CompletedHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS) | Self-Directed ViolenceUnited States
-
National Institute of Allergy and Infectious Diseases...CompletedHuman Immunodeficiency Virus | Acquired Immune Deficiency Syndrome Virus | Acquired Immunodeficiency Syndrome Virus | AIDS Virus | Human Immunodeficiency VirusesUnited States
-
Columbia UniversityNational Institute of Mental Health (NIMH); Ministry of Health and Social Welfare...CompletedHIV (Human Immunodeficiency Virus) | AIDS (Acquired Immunodeficiency Syndrome)Tanzania
-
Janssen-Cilag International NVCompletedHIV Infections | Human Immunodeficiency Virus | Acquired Immunodeficiency Syndrome Virus | AIDS VirusUnited Kingdom, Belgium, Germany, Spain, Portugal, Israel, Denmark, Russian Federation, Austria, Hungary, Switzerland
-
Emory UniversityGrady Health SystemCompleted
-
Columbia UniversityNational Institute of Nursing Research (NINR)CompletedHIV (Human Immunodeficiency Virus) | AIDS (Acquired Immunodeficiency Syndrome)United States
-
St. Jude Children's Research HospitalCompletedHuman Immunodeficiency Virus (HIV) | Acquired Immunodeficiency Syndrome (AIDS)United States
-
Janssen-Cilag International NVCompletedHuman Immunodeficiency Virus (HIV) Infections | Acquired Immunodeficiency Syndrome (AIDS) VirusFrance, United Kingdom, Belgium, Germany, Spain, Switzerland, Denmark, Israel, Austria, Poland, Hungary, Sweden, Ireland
-
Columbia UniversityNational Institute of Mental Health (NIMH)CompletedHuman Immunodeficiency Virus (HIV) | Acquired Immune Deficiency Syndrome (AIDS)Ethiopia
-
Columbia UniversityCenters for Disease Control and PreventionCompletedHuman Immunodeficiency Virus (HIV) | Acquired Immune Deficiency Syndrome (AIDS)South Africa
Clinical Trials on etravirine (ETR, TMC125)
-
National Institute of Allergy and Infectious Diseases...CompletedHIV InfectionsUnited States, Brazil, South Africa
-
Tibotec Pharmaceuticals, IrelandCompleted
-
Tibotec Pharmaceuticals, IrelandCompletedHIV-1United States, France, Spain, Portugal, Canada, United Kingdom, South Africa, Argentina, Brazil, Puerto Rico, Thailand, Netherlands, Romania
-
Tibotec Pharmaceuticals, IrelandCompleted
-
Tibotec Pharmaceuticals, IrelandCompleted
-
Tibotec Pharmaceuticals, IrelandCompleted
-
Tibotec Pharmaceuticals, IrelandCompletedHIV-1United States, Belgium, Germany, Taiwan, Spain, Mexico, Turkey, Canada, Netherlands, Denmark, Greece, Sweden, Korea, Republic of, Russian Federation, Puerto Rico, Luxembourg
-
Tibotec Pharmaceuticals, IrelandCompleted
-
Tibotec Pharmaceuticals, IrelandCompletedHIV-1United States, Canada, France, Belgium, Germany, Spain, Argentina, Chile, Panama, Brazil, Puerto Rico, Thailand, Mexico, Australia