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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV
ClinicalTrials.gov Identifier:
NCT00903682
First received: May 14, 2009
Last updated: January 7, 2013
Last verified: January 2013
Results First Received: February 10, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Conditions: HIV Infection
HIV
Acquired Immunodeficiency Syndrome
Interventions: Drug: etravirine (ETR, TMC125)
Drug: efavirenz (EFV)

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Etravirine Etravirine (ETR TMC125) 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

Participant Flow:   Overall Study
    Etravirine     Efavirenz  
STARTED     79     78  
COMPLETED     63     63  
NOT COMPLETED     16     15  
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  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Etravirine ETR 400mg once daily (4x100mg tablet) + 2 NRTIs + 1 EFV placebo tablet for 48 weeks
Efavirenz EFV 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Total Total of all reporting groups

Baseline Measures
    Etravirine     Efavirenz     Total  
Number of Participants  
[units: participants]
  79     78     157  
Age  
[units: participants]
     
<=18 years     1     0     1  
Between 18 and 65 years     78     77     155  
>=65 years     0     1     1  
Age  
[units: years]
Mean ± Standard Deviation
  37.7  ± 9.52     37.6  ± 9.82     37.6  ± 9.64  
Gender  
[units: participants]
     
Female     12     18     30  
Male     67     60     127  
Region of Enrollment  
[units: 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  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   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 ]

Measure Type Primary
Measure Title Proportion of Patients With at Least 1 Treatment-emergent Grade 1-4 Central Nervous System or Psychiatric Adverse Event
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Etravirine Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks

Measured Values
    Etravirine     Efavirenz  
Number of Participants Analyzed  
[units: participants]
  79     78  
Proportion of Patients With at Least 1 Treatment-emergent Grade 1-4 Central Nervous System or Psychiatric Adverse Event  
[units: percentage of patients]
  16.5     46.2  


Statistical Analysis 1 for Proportion of Patients With at Least 1 Treatment-emergent Grade 1-4 Central Nervous System or Psychiatric Adverse Event
Groups [1] All groups
Method [2] Regression, Logistic
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



2.  Secondary:   Antiviral Activity of ETR vs. EFV   [ Time Frame: between baseline and week 48 ]

Measure Type Secondary
Measure Title Antiviral Activity of ETR vs. EFV
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol.

Reporting Groups
  Description
Etravirine Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks

Measured Values
    Etravirine     Efavirenz  
Number of Participants Analyzed  
[units: participants]
  79     78  
Antiviral Activity of ETR vs. EFV  
[units: Number of participants]
  60     58  


Statistical Analysis 1 for Antiviral Activity of ETR vs. EFV
Groups [1] All groups
Difference in proportion of response [2] 1.61
95% Confidence Interval ( -12.00 to 15.23 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  Difference in proportion of response ETR minus EFV



3.  Secondary:   Antiviral Activity of ETR vs. EFV   [ Time Frame: between baseline and week 48 ]

Measure Type Secondary
Measure Title Antiviral Activity of ETR vs. EFV
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol.

Reporting Groups
  Description
Etravirine Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks

Measured Values
    Etravirine     Efavirenz  
Number of Participants Analyzed  
[units: participants]
  79     78  
Antiviral Activity of ETR vs. EFV  
[units: Number of participants]
  64     62  

No statistical analysis provided for Antiviral Activity of ETR vs. EFV



4.  Secondary:   Mean Change From Baseline in Neuropsychiatric and Total Tolerabililty Score   [ Time Frame: between baseline and week 48 ]

Measure Type Secondary
Measure Title Mean Change From Baseline in Neuropsychiatric and Total Tolerabililty Score
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol.

Reporting Groups
  Description
Etravirine Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks

Measured Values
    Etravirine     Efavirenz  
Number of Participants Analyzed  
[units: participants]
  75     74  
Mean Change From Baseline in Neuropsychiatric and Total Tolerabililty Score  
[units: points on a scale]
Mean ± Standard Error
   
Total Tolerability Score     -0.04  ± 0.03     -0.01  ± 0.04  
Neuropsychiatric Tolerability Score     -0.04  ± 0.06     -0.07  ± 0.07  

No statistical analysis provided for Mean Change From Baseline in Neuropsychiatric and Total Tolerabililty Score



5.  Secondary:   Neuropsychiatric Adverse Events by Week 48   [ Time Frame: from baseline to week 48 ]

Measure Type Secondary
Measure Title Neuropsychiatric Adverse Events by Week 48
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol.

Reporting Groups
  Description
Etravirine Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks

Measured Values
    Etravirine     Efavirenz  
Number of Participants Analyzed  
[units: participants]
  79     78  
Neuropsychiatric Adverse Events by Week 48  
[units: percentage of patients]
  20.3     52.6  

No statistical analysis provided for Neuropsychiatric Adverse Events by Week 48



6.  Secondary:   Mean Change From Baseline in CD4+ Cell Count   [ Time Frame: at baseline and week 2, 6, 12, 24, 36 and 48 ]

Measure Type Secondary
Measure Title Mean Change From Baseline in CD4+ Cell Count
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol

Reporting Groups
  Description
Etravirine Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks

Measured Values
    Etravirine     Efavirenz  
Number of Participants Analyzed  
[units: participants]
  74     74  
Mean Change From Baseline in CD4+ Cell Count  
[units: number of cells/L (x10^6)]
Mean ± Standard Error
   
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  

No statistical analysis provided for Mean Change From Baseline in CD4+ Cell Count



7.  Secondary:   Resistance Determinations   [ Time Frame: at baseline and all subsequent visits until week 48 in case if virologic failure ]

Measure Type Secondary
Measure Title Resistance Determinations
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol

Reporting Groups
  Description
Etravirine Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks
Efavirenz Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks

Measured Values
    Etravirine     Efavirenz  
Number of Participants Analyzed  
[units: participants]
  79     78  
Resistance Determinations  
[units: 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  

No statistical analysis provided for Resistance Determinations




  Serious Adverse Events


  Other Adverse Events


  More Information
  Hide More Information

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: EMEA Medical Affairs Director Virology
Organization: Janssen-Cilag EMEA
phone: +31 6 542 454 37


Publications of Results:

Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT00903682     History of Changes
Other Study ID Numbers: CR015751, TMC125VIR2038, 2008-008655-42
Study First Received: May 14, 2009
Results First Received: February 10, 2011
Last Updated: January 7, 2013
Health Authority: Belgium: Ministry of Social Affairs, Public Health and the Environment