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
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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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
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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.
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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
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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 ]
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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:
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[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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2.  Secondary:   Antiviral Activity of ETR vs. EFV   [ Time Frame: between baseline and week 48 ]

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

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

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

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


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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