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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)

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ClinicalTrials.gov Identifier: NCT00903682
Recruitment Status : Completed
First Posted : May 18, 2009
Results First Posted : March 7, 2011
Last Update Posted : January 14, 2013
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions HIV Infection
HIV
Acquired Immunodeficiency Syndrome
Interventions Drug: etravirine (ETR, TMC125)
Drug: efavirenz (EFV)
Enrollment 157
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Etravirine Efavirenz
Hide Arm/Group Description Etravirine (ETR TMC125) 400mg once daily (4x100mg tablet) + 2 NRTI + 1 EFV placebo tablet for 48 weeks Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Period Title: Overall Study
Started 79 78
Completed 63 63
Not Completed 16 15
Reason Not Completed
Adverse Event             6             13
Lost to Follow-up             1             0
Withdrawal by Subject             5             0
Pregnancy             0             1
Subject Reached A Virologic Endpoint             1             1
Subject Non-Compliant             1             0
Patient Couldn't Come For The Visit Due             1             0
For Resistent Profile (Excl Crit 2 Met)             1             0
Arm/Group Title Etravirine Efavirenz Total
Hide Arm/Group Description ETR 400mg once daily (4x100mg tablet) + 2 NRTIs + 1 EFV placebo tablet for 48 weeks EFV 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks Total of all reporting groups
Overall Number of Baseline Participants 79 78 157
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 78 participants 157 participants
<=18 years
1
   1.3%
0
   0.0%
1
   0.6%
Between 18 and 65 years
78
  98.7%
77
  98.7%
155
  98.7%
>=65 years
0
   0.0%
1
   1.3%
1
   0.6%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 79 participants 78 participants 157 participants
37.7  (9.52) 37.6  (9.82) 37.6  (9.64)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 78 participants 157 participants
Female
12
  15.2%
18
  23.1%
30
  19.1%
Male
67
  84.8%
60
  76.9%
127
  80.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 79 participants 78 participants 157 participants
Austria 3 4 7
Denmark 0 2 2
France 9 9 18
Germany 16 13 29
Hungary 5 3 8
Israel 4 5 9
Italy 9 6 15
Romania 6 10 16
Russia 9 8 17
Spain 12 9 21
Switzerland 1 3 4
UK 5 6 11
1.Primary Outcome
Title Proportion of Patients With at Least 1 Treatment-emergent Grade 1-4 Central Nervous System or Psychiatric Adverse Event
Hide Description 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.
Time Frame between baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population has been defined as the set of all patients who were randomized and who have taken at least one dose of trial medication, regardless of their compliance with the protocol.
Arm/Group Title Etravirine Efavirenz
Hide Arm/Group Description:
Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Overall Number of Participants Analyzed 79 78
Measure Type: Number
Unit of Measure: percentage of patients
16.5 46.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etravirine, Efavirenz
Comments The hypothesis is that the proportion of patients with at least 1 treatment-emergent Grade 1-4 neuropsychiatric adverse event, observed between Baseline through Week 12 and judged to be at least possibly drug-related, is significantly lower in the ETR arm than in the EFV arm. Assuming a significance level of 5%, a sample size of 75 subjects per arm would provide over 90% power to detect a 29% difference in treatment-emergent, drug-related Grade 1-4 neuropsychiatric adverse events.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
2.Secondary Outcome
Title Antiviral Activity of ETR vs. EFV
Hide Description 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)
Time Frame between baseline and week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol.
Arm/Group Title Etravirine Efavirenz
Hide Arm/Group Description:
Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Overall Number of Participants Analyzed 79 78
Measure Type: Number
Unit of Measure: Number of participants
60 58
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etravirine, Efavirenz
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportion of response
Estimated Value 1.61
Confidence Interval (2-Sided) 95%
-12.00 to 15.23
Estimation Comments Difference in proportion of response ETR minus EFV
3.Secondary Outcome
Title Antiviral Activity of ETR vs. EFV
Hide Description 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)
Time Frame between baseline and week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol.
Arm/Group Title Etravirine Efavirenz
Hide Arm/Group Description:
Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Overall Number of Participants Analyzed 79 78
Measure Type: Number
Unit of Measure: Number of participants
64 62
4.Secondary Outcome
Title Mean Change From Baseline in Neuropsychiatric and Total Tolerabililty Score
Hide Description 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)
Time Frame between baseline and week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol.
Arm/Group Title Etravirine Efavirenz
Hide Arm/Group Description:
Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Overall Number of Participants Analyzed 75 74
Mean (Standard Error)
Unit of Measure: points on a scale
Total Tolerability Score -0.04  (0.03) -0.01  (0.04)
Neuropsychiatric Tolerability Score -0.04  (0.06) -0.07  (0.07)
5.Secondary Outcome
Title Neuropsychiatric Adverse Events by Week 48
Hide Description 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.
Time Frame from baseline to week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol.
Arm/Group Title Etravirine Efavirenz
Hide Arm/Group Description:
Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Overall Number of Participants Analyzed 79 78
Measure Type: Number
Unit of Measure: percentage of patients
20.3 52.6
6.Secondary Outcome
Title Mean Change From Baseline in CD4+ Cell Count
Hide Description 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.
Time Frame at baseline and week 2, 6, 12, 24, 36 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol
Arm/Group Title Etravirine Efavirenz
Hide Arm/Group Description:
Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Overall Number of Participants Analyzed 74 74
Mean (Standard Error)
Unit of Measure: number of cells/L (x10^6)
Week 2 69.96  (9.82) 72.45  (11.33)
Week 6 128.14  (13.19) 121.62  (13.96)
Week 12 143.24  (13.56) 151.46  (16.68)
Week 24 182.01  (16.48) 174.08  (14.85)
Week 36 213.45  (19.11) 180.18  (15.12)
Week 48 205.11  (20.07) 221.39  (18.31)
7.Secondary Outcome
Title Resistance Determinations
Hide Description 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)
Time Frame at baseline and all subsequent visits until week 48 in case if virologic failure
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol
Arm/Group Title Etravirine Efavirenz
Hide Arm/Group Description:
Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Overall Number of Participants Analyzed 79 78
Measure Type: Number
Unit of Measure: number of participants
>= 1 successful genotype after baseline 11 9
>= 1 IAS-USA NRTI RAMs 0 2
>= 1 NRTI Surveillance Drug Resistance Mutation 0 2
>= 1 NNRTI RAMs 2 3
no NRTI or NNRTI RAMs 9 6
Time Frame Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Etravirine Efavirenz
Hide Arm/Group Description ETR 400mg once daily (4x100mg tablet) + 2 NRTIs + 1 EFV placebo tablet for 48 weeks EFV 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
All-Cause Mortality
Etravirine Efavirenz
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Etravirine Efavirenz
Affected / at Risk (%) Affected / at Risk (%)
Total   11/79 (13.92%)   6/78 (7.69%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/79 (1.27%)  0/78 (0.00%) 
Eye disorders     
Conjunctivitis * 1  1/79 (1.27%)  0/78 (0.00%) 
Gastrointestinal disorders     
Anal Fissure * 1  1/79 (1.27%)  0/78 (0.00%) 
Stomatitis * 1  1/79 (1.27%)  0/78 (0.00%) 
General disorders     
Pyrexia * 1  1/79 (1.27%)  0/78 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis * 1  1/79 (1.27%)  0/78 (0.00%) 
Infections and infestations     
Pneumonia * 1  1/79 (1.27%)  0/78 (0.00%) 
Pulmonary Tuberculosis * 1  0/79 (0.00%)  1/78 (1.28%) 
Anal Abscess * 1  0/79 (0.00%)  1/78 (1.28%) 
Anogenital Warts * 1  1/79 (1.27%)  0/78 (0.00%) 
Secondary Syphilis * 1  1/79 (1.27%)  0/78 (0.00%) 
Investigations     
Alanine Aminotransferase Increased * 1  1/79 (1.27%)  1/78 (1.28%) 
Aspartate Aminotransferase Increased * 1  0/79 (0.00%)  1/78 (1.28%) 
Musculoskeletal and connective tissue disorders     
Joint Ankylosis * 1  1/79 (1.27%)  0/78 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal Cell Carcinoma * 1  0/79 (0.00%)  1/78 (1.28%) 
Non-Hodgkin's Lymphoma * 1  1/79 (1.27%)  0/78 (0.00%) 
Squamous Cell Carcinoma * 1  0/79 (0.00%)  1/78 (1.28%) 
Benign Ovarian Tumour * 1  1/79 (1.27%)  0/78 (0.00%) 
Lymphoma * 1  1/79 (1.27%)  0/78 (0.00%) 
Uterine Leiomyoma * 1  1/79 (1.27%)  0/78 (0.00%) 
Renal and urinary disorders     
Urethral Stenosis * 1  1/79 (1.27%)  0/78 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pneumothorax * 1  0/79 (0.00%)  1/78 (1.28%) 
Laryngeal Inflammation * 1  1/79 (1.27%)  0/78 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash * 1  1/79 (1.27%)  0/78 (0.00%) 
Surgical and medical procedures     
Abortion Induced * 1  0/79 (0.00%)  1/78 (1.28%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 12.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Etravirine Efavirenz
Affected / at Risk (%) Affected / at Risk (%)
Total   54/79 (68.35%)   62/78 (79.49%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/79 (1.27%)  4/78 (5.13%) 
Ear and labyrinth disorders     
Vertigo * 1  2/79 (2.53%)  4/78 (5.13%) 
Gastrointestinal disorders     
Diarrhoea * 1  8/79 (10.13%)  9/78 (11.54%) 
Nausea * 1  7/79 (8.86%)  13/78 (16.67%) 
Vomiting * 1  2/79 (2.53%)  6/78 (7.69%) 
Dyspepsia * 1  6/79 (7.59%)  3/78 (3.85%) 
General disorders     
Asthenia * 1  3/79 (3.80%)  5/78 (6.41%) 
Pyrexia * 1  5/79 (6.33%)  5/78 (6.41%) 
Fatigue * 1  5/79 (6.33%)  6/78 (7.69%) 
Infections and infestations     
Influenza * 1  6/79 (7.59%)  1/78 (1.28%) 
Nasopharyngitis * 1  17/79 (21.52%)  6/78 (7.69%) 
Bronchitis * 1  5/79 (6.33%)  5/78 (6.41%) 
Pharyngitis * 1  4/79 (5.06%)  2/78 (2.56%) 
Metabolism and nutrition disorders     
Hypercholesterolaemia * 1  3/79 (3.80%)  7/78 (8.97%) 
Hypertriglyceridaemia * 1  2/79 (2.53%)  4/78 (5.13%) 
Musculoskeletal and connective tissue disorders     
Back Pain * 1  7/79 (8.86%)  3/78 (3.85%) 
Nervous system disorders     
Dizziness * 1  3/79 (3.80%)  17/78 (21.79%) 
Headache * 1  13/79 (16.46%)  11/78 (14.10%) 
Somnolence * 1  2/79 (2.53%)  5/78 (6.41%) 
Disturbance in Attention * 1  1/79 (1.27%)  4/78 (5.13%) 
Psychiatric disorders     
Abnormal Dreams * 1  2/79 (2.53%)  9/78 (11.54%) 
Insomnia * 1  2/79 (2.53%)  8/78 (10.26%) 
Nightmare * 1  3/79 (3.80%)  7/78 (8.97%) 
Sleep Disorder * 1  4/79 (5.06%)  8/78 (10.26%) 
Anxiety * 1  1/79 (1.27%)  4/78 (5.13%) 
Depression * 1  1/79 (1.27%)  5/78 (6.41%) 
Skin and subcutaneous tissue disorders     
Pruritus * 1  5/79 (6.33%)  7/78 (8.97%) 
Rash * 1  5/79 (6.33%)  2/78 (2.56%) 
Vascular disorders     
Hot Flush * 1  0/79 (0.00%)  4/78 (5.13%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 12.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
A copy of the manuscript must be provided to the Sponsor for review at least 60 days prior to submission for publication or presentation. No paper that incorporates Confidential Information will be submitted for publication without Sponsor’s prior written consent. If requested in writing, such publication will be withheld for up to an additional 60 calendar days. A publication from the individual Study site data will not be published until the combined results have been published.
Results Point of Contact
Name/Title: EMEA Medical Affairs Director Virology
Organization: Janssen-Cilag EMEA
Phone: +31 6 542 454 37
Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT00903682     History of Changes
Other Study ID Numbers: CR015751
TMC125VIR2038 ( Other Identifier: Janssen-Cilag International NV )
2008-008655-42 ( EudraCT Number )
First Submitted: May 14, 2009
First Posted: May 18, 2009
Results First Submitted: February 10, 2011
Results First Posted: March 7, 2011
Last Update Posted: January 14, 2013