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Evaluating Once Daily Etravirine in Treatment-Naive Adults With HIV Infection

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ClinicalTrials.gov Identifier: NCT00959894
Recruitment Status : Completed
First Posted : August 17, 2009
Results First Posted : May 13, 2015
Last Update Posted : June 6, 2016
Sponsor:
Collaborator:
Janssen Pharmaceuticals
Information provided by (Responsible Party):
Michelle Floris-Moore, MD, University of North Carolina, Chapel Hill

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: Etravirine (Intelence)
Drug: Truvada
Enrollment 80

Recruitment Details  
Pre-assignment Details 80 participants were enrolled, however 1 participant was found to be ineligible on the day of entry and never started study medication (had developed acute renal failure and therefore no longer met eligibility requirements).
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Period Title: Overall Study
Started 79 [1]
Completed 63
Not Completed 16
Reason Not Completed
Lost to Follow-up             10
Adverse Event             3
Withdrawal by Subject             1
Need for contraindicated medication             1
Subject moved out of town             1
[1]
One (1) additional subject became ineligible on the day of entry and never started study medication.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Baseline Participants 79
Hide Baseline Analysis Population Description
All participants who received at least one dose of study medication (etravirine 400 mg given once daily with with one tablet of fixed dose tenofovir/emtricitabine).
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants
<=18 years
0
   0.0%
Between 18 and 65 years
79
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 79 participants
29
(23 to 44)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants
Female
8
  10.1%
Male
71
  89.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 79 participants
79
1.Primary Outcome
Title The Antiretroviral Activity of Etravirine 400 mg Given Once Daily, With Fixed-dose Truvada Once Daily, Among Treatment-naïve HIV-1 Infected Adults as Measured by the Percentage of Participants With HIV RNA < 50 Copies/mL at Week 24
Hide Description The primary study endpoint was the proportion of participants who achieved HIV-1 RNA <50 copies/ml at Week 24 of study participation. The per-protocol primary analysis was conducted intention-to-treat, with missing evaluations counted as failures. Achievement of HIV-1 viral load below 50 copies/ml was defined as having HIV-1 RNA <50 copies/ml during the Week 24 analysis window (>18 and <30 weeks post-entry).
Time Frame 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of 79 participants who initiated study medications, 74 had a Week 24 HIV-1 RNA measurement. The primary analysis was conducted intention-to-treat, with missing evaluations counted as failure.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 79
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.87
(0.78 to 0.94)
2.Secondary Outcome
Title The Proportion of Participants With HIV RNA <50 Copies/mL at Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <50 copies/ml at Week 48 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.
Time Frame 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of 79 participants who initiated study medications, 69 had a Week 48 HIV-1 RNA measurement (4 participants had discontinued the study, 3 were lost to follow-up, and 3 missed the Week 48 visit). The analysis was conducted intention-to-treat, with missing evaluations counted as failure.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 79
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.77
(0.66 to 0.86)
3.Secondary Outcome
Title The Proportion of Participants With HIV RNA <50 Copies/mL at Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <50 copies/ml at Week 96 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.
Time Frame 96 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of 79 participants who initiated study medications, 63 had a Week 96 HIV-1 RNA measurement (6 participants had discontinued the study and 10 were lost to follow-up). The analysis was conducted intention-to-treat, with missing evaluations counted as failure.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 79
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.71
(0.60 to 0.81)
4.Secondary Outcome
Title The Proportion of Participants With HIV RNA <200 Copies/mL at Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <200 copies/ml at Week 24 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.
Time Frame 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of 79 participants who initiated study medications, 74 had a Week 24 HIV-1 RNA measurement (3 participants had discontinued the study, 1 was lost to follow-up, and 1 missed the Week 24 visit). The analysis was conducted intention-to-treat, with missing evaluations counted as failure.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 79
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.89
(0.79 to 0.95)
5.Secondary Outcome
Title The Proportion of Participants With HIV RNA <200 Copies/mL at Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <200 copies/ml at Week 48 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.
Time Frame 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of 79 participants who initiated study medications, 69 had a Week 48 HIV-1 RNA measurement (4 participants had discontinued the study, 3 were lost to follow-up, and 3 missed the Week 48 visit). The analysis was conducted intention-to-treat, with missing evaluations counted as failure.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 79
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.82
(0.72 to 0.90)
6.Secondary Outcome
Title The Proportion of Participants With HIV RNA <200 Copies/mL at Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA 200 copies/ml at Week 96 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.
Time Frame 96 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of 79 participants who initiated study medications, 63 had a Week 96 HIV-1 RNA measurement (6 participants had discontinued the study and 10 were lost to follow-up). The analysis was conducted intention-to-treat, with missing evaluations counted as failure.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 79
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.77
(0.66 to 0.86)
7.Secondary Outcome
Title Change in CD4+ Cell Count From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description The per-protocol analysis of change in CD4+ cell count from baseline to Week 24 was calculated using the measurement closest to schedule and within the analysis window, and quantified with an estimated median and distribution-free 95% confidence interval (CI).
Time Frame Baseline to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of 79 participants who initiated study medications, 73 had a Week 24 CD4+ cell count measurement (4 discontinued study participation prior to Week 24,1 missed the Week 24 visit, and 1 did not have a Week 24 CD4+ cell count measurement).
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 73
Median (95% Confidence Interval)
Unit of Measure: cells/uL
156
(113 to 200)
8.Secondary Outcome
Title Change in CD4+ Cell Count From Baseline to Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description The per-protocol intention-to-treat analysis of change in CD4+ cell count from baseline to Week 48 was calculated using the measurement closest to schedule and within the analysis window, and quantified with an estimated median and distribution-free 95% CI.
Time Frame Baseline to 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of 79 participants who initiated study medications, 69 had a Week 48 CD4+ cell count measurement (4 discontinued study participation prior to Week 48 visit, 3 were lost to follow-up, and 3 missed the Week 48 visit).
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 69
Median (95% Confidence Interval)
Unit of Measure: cells/uL
163
(136 to 203)
9.Secondary Outcome
Title Change in CD4+ Cell Count From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description The per-protocol intention-to-treat analysis of change in CD4+ cell count from baseline to Week 96 was calculated using the measurement closest to schedule and within the analysis window, and quantified with an estimated median and distribution-free 95% CI.
Time Frame Baseline to 96 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of 79 participants who initiated study medications, 63 had a Week 48 CD4+ cell count measurement (6 discontinued study participation prior to Week 96 and 10 were lost to follow-up).
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 63
Median (95% Confidence Interval)
Unit of Measure: cells/uL
224
(188 to 266)
10.Secondary Outcome
Title Resistance Mutations in the Subset of Patients With Confirmed Virologic Failure Who Have HIV RNA >500 Copies/mL and Genotype Resistance Results
Hide Description Per-protocol, genotype testing was conducted at confirmation of virologic failure if the confirmatory HIV-1 RNA was above the laboratory-specified threshold of 500 copies/mL. HIV-1 genotype was determined using the TRUGENE® HIV-1 assay (Siemens Healthcare Diagnostics, Tarrytown, NY)
Time Frame 96 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of participants with confirmed virologic failure, 8 had HIV-1 RNA levels ≥ 500 copies/mL and 6 of these had viral genotype results available (1 had previously discontinued study medication at Week 2, and 1 was missing).
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: participants
Y181C 1
E138K 1
E138K, Y181C, M230L, M184I, K219E, V75I 1
No resistance-associated mutations detected 3
11.Secondary Outcome
Title Tolerability of Etravirine in HIV-1 Infected Adults Initiating Antiretroviral Therapy
Hide Description

The safety/tolerability endpoint was defined as the first grade 3 or higher sign, symptom or laboratory abnormality that was at least one grade higher than baseline among participants ever exposed to etravirine (regardless of treatment status), or permanent discontinuation of etravirine due to any toxicity (regardless of grade). Modification of tenofovir/emtricitabine was not a safety/tolerability event.

The Kaplan-Meier method was used to estimate the proportion of participants ever exposed to etravirine who remained event-free through Week 96, with a 95% CI using Greenwood’s variance estimate and a log-log transformation. Time was handled as continuous (weeks from treatment start to event or censoring).

Time Frame 96 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population for this outcome is all participants who received at least one dose of etravirine, regardless of whether or not they were still receiving etravirine at the time of the safety/tolerability event.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 79
Measure Type: Number
Unit of Measure: participants
At least one safety/tolerability event 23
Signs or Symptoms 13
Laboratory Abnormalities 10
12.Secondary Outcome
Title Probability of Remaining Free of a Safety/Tolerability Event at 96 Weeks
Hide Description The Kaplan-Meier method was used to estimate the proportion of participants ever exposed to etravirine who remained event-free through Week 96, with a 95% CI using Greenwood’s variance estimate and a log-log transformation. Time was handled as continuous (weeks from treatment start to event or censoring).
Time Frame 96 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population for this outcome is all participants who received at least one dose of etravirine, regardless of whether or not they were still receiving etravirine at the time of the safety/tolerability event.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 79
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.69
(0.57 to 0.78)
13.Secondary Outcome
Title Change in the Lipid Profile and Glucose Metabolism, in a Subgroup of up to 40 Participants, From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description Metabolic data analyses were conducted as-treated. Changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.
Time Frame Baseline to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This per-protocol sub-study analysis of metabolic outcomes was conducted in the as-treated population in the metabolic sub-study.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 36
Median (Inter-Quartile Range)
Unit of Measure: mg/dL
Total cholesterol
-7
(-17 to 4)
HDL-cholesterol
1
(-4 to 9)
LDL-cholesterol
-9
(-14 to -1)
Triglycerides
-16
(-33 to 18)
Fasting glucose
1
(-6 to 9)
14.Secondary Outcome
Title Change in Glucose Metabolism (Insulin Resistance), in a Subgroup of up to 40 Participants, From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description Metabolic data analyses were conducted as-treated. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5. Changes from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.
Time Frame Baseline to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This per-protocol sub-study analysis of metabolic outcomes was conducted in the as-treated population in the metabolic sub-study.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 27
Median (Inter-Quartile Range)
Unit of Measure: µU/ml*mmol/L
-0.08
(-0.72 to 0.27)
15.Secondary Outcome
Title Change in the Lipid Profile and Glucose Metabolism, in a Subgroup of up to 40 Participants, From Baseline to Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description Metabolic data analyses were conducted as-treated. Changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.
Time Frame Baseline to 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This per-protocol sub-study analysis of metabolic outcomes was conducted in the as-treated population in the metabolic sub-study.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 32
Median (Inter-Quartile Range)
Unit of Measure: mg/dL
Total cholesterol
6
(-14 to 21)
HDL-cholesterol
5
(-2 to 12)
LDL-cholesterol
-1
(-10 to 14)
Triglycerides
-10
(-26 to 21)
Fasting glucose
2
(-5 to 6)
16.Secondary Outcome
Title Change in Glucose Metabolism (Insulin Resistance), in a Subgroup of up to 40 Participants, From Baseline to Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description Metabolic data analyses were conducted as-treated. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5. Changes from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.
Time Frame Baseline to 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This per-protocol sub-study analysis of metabolic outcomes was conducted in the as-treated population in the metabolic sub-study.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 23
Median (Inter-Quartile Range)
Unit of Measure: µU/ml*mmol/L
0.71
(-0.01 to 2.21)
17.Secondary Outcome
Title Change in the Lipid Profile and Glucose Metabolism, in a Subgroup of up to 40 Participants, From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description Metabolic data analyses were conducted as-treated. Changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5.
Time Frame Baseline to 96 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This per-protocol sub-study analysis of metabolic outcomes was conducted in the as-treated population in the metabolic sub-study.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 22
Median (Inter-Quartile Range)
Unit of Measure: mg/dL
Total cholesterol
6
(-14 to 21)
HDL-cholesterol
4
(-3 to 15)
LDL-cholesterol
-5
(-26 to 7)
Triglycerides
3
(-18 to 16)
Fasting glucose
2
(-6 to 6)
18.Secondary Outcome
Title Change in Glucose Metabolism (Insulin Resistance), in a Subgroup of up to 40 Participants, From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description Metabolic data analyses were conducted as-treated. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5. Changes from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.
Time Frame Baseline to 96 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This per-protocol sub-study analysis of metabolic outcomes was conducted in the as-treated population in the metabolic sub-study.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 18
Median (Inter-Quartile Range)
Unit of Measure: µU/ml*mmol/L
0.23
(-0.67 to 1.15)
19.Secondary Outcome
Title Change in Limb and Trunk Fat Distribution as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description Changes from baseline to follow-up in limb fat, trunk fat, total body fat, and lean mass were calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.
Time Frame Baseline to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This per-protocol sub-study analysis was conducted in the as-treated population of participants in the metabolic sub-study.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 37
Median (95% Confidence Interval)
Unit of Measure: percentage of body fat
Total body fat
0.43
(-0.63 to 1.10)
Limb fat
0.48
(-0.64 to 0.99)
Trunk fat
0.32
(-0.41 to 1.66)
20.Secondary Outcome
Title Change in Limb and Trunk Fat Distribution as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description Changes from baseline to follow-up in limb fat, trunk fat, total body fat, and lean mass were calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.
Time Frame Baseline to 96 weeks
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Hide Analysis Population Description
This per-protocol sub-study analysis was conducted in the as-treated population of participants in the metabolic sub-study.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 25
Median (95% Confidence Interval)
Unit of Measure: percentage of body fat
Total body fat
1.44
(-0.40 to 3.86)
Limb fat
0.82
(-1.55 to 4.12)
Trunk fat
1.93
(0.31 to 4.67)
21.Secondary Outcome
Title Change in Fat Mass Ratio as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description Change from baseline to follow-up in fat mass ratio was calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Fat mass ratio was calculated as the ratio of trunk fat percentage and lower limb fat percentage (% trunk fat mass / % lower limb fat mass). Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.
Time Frame Baseline to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This per-protocol sub-study analysis was conducted in the as-treated population of participants in the metabolic sub-study.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 37
Median (95% Confidence Interval)
Unit of Measure: ratio of trunk fat % : lower limb fat %
0.02
(-0.01 to 0.09)
22.Secondary Outcome
Title Pharmacokinetics of Etravirine in Genital Secretions of up to 10 Men and up to 10 Women at Week 4 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description This secondary outcome measure assessed the ratio of semen:plasma concentration of etravirine in paired semen and plasma samples collected from 14 male participants at Week 4 of treatment with etravirine and fixed dose tenofovir/emtricitabine.
Time Frame 4 weeks
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Hide Analysis Population Description
Of 79 participants who initiated study medications, 14 provided paired plasma and genital secretion samples. The goal was to enroll a total of 20 participants (10 men and 10 women) into the genital secretion sub-group, however no women enrolled into this subgroup. Data are presented for semen and plasma etravirine concentrations for 14 men.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 14
Median (Inter-Quartile Range)
Unit of Measure: ratio of semen:plasma drug concentration
0.192
(.138 to .309)
23.Secondary Outcome
Title Change in Fat Mass Ratio as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine
Hide Description Change from baseline to follow-up in fat mass ratio was calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Fat mass ratio was calculated as the ratio of trunk fat percentage and lower limb fat percentage (% trunk fat mass / % lower limb fat mass). Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.
Time Frame Baseline to 96 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This per-protocol sub-study analysis was conducted in the as-treated population of participants in the metabolic sub-study.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 25
Median (95% Confidence Interval)
Unit of Measure: ratio of trunk fat % : lower limb fat %
0.06
(0.02 to 0.09)
24.Secondary Outcome
Title Population Pharmacokinetics of Etravirine 400 mg Once Daily, in Combination With Fixed-dose Emtricitabine-tenofovir Among Treatment-naïve HIV-1 Infected Adults
Hide Description Population pharmacokinetics were calculated using sparse sampling. Plasma concentrations of etravirine measured in samples from participants who provided blood samples at multiple study visits, with variation in sampling times relative to dosing of etravirine used to cover the spectrum of the dosing schedule. Model simulations and fitting were performed with NONMEM ® 7.3. (ICON, plc) and model exploration was performed with Berkeley Madonna (Berkeley, CA, USA)
Time Frame At or after 4 weeks
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Hide Analysis Population Description
57 participants who provided samples at multiple time points relative to etravirine dosing.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Truvada: Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 57
Median (Inter-Quartile Range)
Unit of Measure: ng/mL
Etravirine trough plasma concentration
217.47
(154.29 to 295.31)
Etravirine peak plasma concentration
480.99
(416.77 to 559.49)
25.Secondary Outcome
Title Population Pharmacokinetics of Etravirine 400 mg Once Daily, in Combination With Fixed-dose Emtricitabine-tenofovir Among Treatment-naïve HIV-1 Infected Adults: Etravirine AUC-24 Hours at Steady State
Hide Description Population pharmacokinetics were calculated using sparse sampling. Plasma concentrations of etravirine measured in samples from participants who provided blood samples at multiple study visits, with variation in sampling times relative to dosing of etravirine used to cover the spectrum of the dosing schedule. Model simulations and fitting were performed with NONMEM ® 7.3. (ICON, plc) and model exploration was performed with Berkeley Madonna (Berkeley, CA, USA)
Time Frame At or after 4 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
57 participants who provided samples at multiple time points relative to etravirine dosing.
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description:

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Truvada: Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

Overall Number of Participants Analyzed 57
Median (Inter-Quartile Range)
Unit of Measure: ng*hr/mL
8024.40
(6410.20 to 9968.28)
Time Frame Up to 96 weeks for each participant
Adverse Event Reporting Description Participants were assessed for adverse events routinely every 4 weeks in first 3 months and every 12 weeks thereafter, by standardized interview & clinical/lab exam. Labs, rash & central nervous system symptoms Grade 2 or above, other symptoms above Grade 2, and any symptom that led to change in study treatment were recorded in the database.
 
Arm/Group Title Etravirine 400 mg Once Daily
Hide Arm/Group Description

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Etravirine (Intelence): Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day

All-Cause Mortality
Etravirine 400 mg Once Daily
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Etravirine 400 mg Once Daily
Affected / at Risk (%) # Events
Total   12/79 (15.19%)    
Gastrointestinal disorders   
Vomiting  1 [1]  1/79 (1.27%)  2
Viral gastroenteritis  1  1/79 (1.27%)  1
Colitis  1  1/79 (1.27%)  1
Infections and infestations   
Cellulitis  1  1/79 (1.27%)  1
Disseminated atypical mycobacterium infection  1  1/79 (1.27%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
malignant melanoma of skin  1  1/79 (1.27%)  1
Squamous cell carcinoma  1 [2]  1/79 (1.27%)  1
Nervous system disorders   
Meningitis  1  1/79 (1.27%)  1
Psychiatric disorders   
Depressive disorder  1  1/79 (1.27%)  1
Renal and urinary disorders   
Renal impairment  1 [3]  1/79 (1.27%)  1
Surgical and medical procedures   
Osteoplasty of the mandible  1  1/79 (1.27%)  1
Hip arthroplasty  1  1/79 (1.27%)  1
Prostatectomy  1  1/79 (1.27%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, SNOMED CT
[1]
Participant had longstanding history of intermittent vomiting prior to study enrollment that fluctuated while on study. He was hospitalized and stopped study drugs since the possibility that drugs were contributing to vomiting could not be excluded.
[2]
Skin lesion present prior to study enrollment, subsequent biopsy revealed squamous cell carcinoma.
[3]
Participant on ACE inhibitor therapy for treatment of hypertension developed renal insufficiency and hyperkalemia, resolved when ACE inhibitor discontinued.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Etravirine 400 mg Once Daily
Affected / at Risk (%) # Events
Total   17/79 (21.52%)    
Blood and lymphatic system disorders   
Neutropenia  1  4/79 (5.06%)  8
Endocrine disorders   
Hyperglycemia  1  4/79 (5.06%)  7
Gastrointestinal disorders   
vomiting  1  4/79 (5.06%)  4
General disorders   
Fatigue  1  4/79 (5.06%)  4
Headache  1  4/79 (5.06%)  4
Hepatobiliary disorders   
Elevated level of transaminase  1 [1]  9/79 (11.39%)  13
Hyperbilirubinemia  1 [2]  6/79 (7.59%)  20
Metabolism and nutrition disorders   
Hyperlipidemia  1  6/79 (7.59%)  9
Skin and subcutaneous tissue disorders   
Rash  1  5/79 (6.33%)  5
Indicates events were collected by systematic assessment
1
Term from vocabulary, SNOMED CT
[1]
One participant was diagnosed with acute hepatitis C at the time of transaminase elevation and was consequently discontinued from the study.
[2]
For two participants hyperbilirubinemia occurred after stopping study drug and starting other antiretrovirals due to virologic failure. One participant had sickle cell disease and elevated indirect bilirubin at entry and subsequent visits.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Michelle Floris-Moore, M.D., M.S.
Organization: UNC School of Medicine
Phone: 919-966-2537
Publications:
Scholler-Gyure M, Kakuda TN, De Smedt G, Woodfall B, Lachaert R, Beets G, Peeters M, Hoetelmans RM. Pharmacokinetics of TMC125 in once- and twice- daily regimens in HIV-1-negative volunteers. Program and Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, 2007 [Abstract A-1427], Chicago IL.
Lalezari J, et al. Pharmacokinetics of once-daily etravirine (ETR) without and with once-daily darunavir/ritonavir (DRV/r) in antiretroviral-naïve HIV-1 infected adults. 9th International Congress on Drug Therapy in HIV Infection 2008; abstract O413.
Responsible Party: Michelle Floris-Moore, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00959894     History of Changes
Other Study ID Numbers: 08-2070
First Submitted: August 14, 2009
First Posted: August 17, 2009
Results First Submitted: March 27, 2015
Results First Posted: May 13, 2015
Last Update Posted: June 6, 2016