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A Study of TMC278 in Human Immunodeficiency Virus Type 1 Infected Patients, Who Are Not Treated With Antiretroviral Medicines

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ClinicalTrials.gov Identifier: NCT00110305
Recruitment Status : Completed
First Posted : May 6, 2005
Results First Posted : October 28, 2013
Last Update Posted : June 25, 2014
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Human Immunodeficiency Virus Type 1
Interventions Drug: TMC278 25 mg
Drug: TMC278 75 mg
Drug: TMC278 150 mg
Drug: Efavirenz
Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs)
Enrollment 368

Recruitment Details 368 participants were enrolled at multiple centers in different countries.
Pre-assignment Details 368 participants were randomly assigned to 4 treatment groups (TMC278 25 mg: 93; TMC278 75 mg: 95; TMC278 150 mg: 91; and Efavirenz: 89). Participant flow through Week 240 was reported for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.
Arm/Group Title All TMC278 Efavirenz
Hide Arm/Group Description TMC278 25 mg, 75 mg, and 150 mg once daily Efavirenz 600 mg once daily
Period Title: Overall Study
Started 279 89
Completed 165 57
Not Completed 114 32
Reason Not Completed
Adverse Event             46             13
Sponsors Decision             1             0
Subject Non-Compliant             9             2
Subject Ineligible To Continue The Trial             2             1
Subject Reached A Virologic Endpoint             21             3
Protocol Violation             0             1
Withdrawal by Subject             7             7
Lost to Follow-up             20             3
Other             8             2
Arm/Group Title TMC278 25 mg TMC278 75 mg TMC 150 mg Efavirenz Total
Hide Arm/Group Description TMC278 25 mg once daily TMC278 75 mg once daily TMC278 150 mg once daily Efavirenz 600 mg once daily Total of all reporting groups
Overall Number of Baseline Participants 93 95 91 89 368
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 93 participants 95 participants 91 participants 89 participants 368 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
92
  98.9%
95
 100.0%
89
  97.8%
89
 100.0%
365
  99.2%
>=65 years
1
   1.1%
0
   0.0%
2
   2.2%
0
   0.0%
3
   0.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 93 participants 95 participants 91 participants 89 participants 368 participants
36.7  (8.9) 36.3  (8.3) 35.9  (9.7) 35.4  (8.1) 36.1  (8.75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 93 participants 95 participants 91 participants 89 participants 368 participants
Female
28
  30.1%
31
  32.6%
33
  36.3%
29
  32.6%
121
  32.9%
Male
65
  69.9%
64
  67.4%
58
  63.7%
60
  67.4%
247
  67.1%
Region Enroll  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 93 participants 95 participants 91 participants 89 participants 368 participants
Asia, South Africa and Uganda 32 32 31 29 124
Europe, USA and Russia 33 33 32 32 130
Latin America 28 30 28 28 114
1.Primary Outcome
Title Number of Participants With Virologic Response at Week 48 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Hide Description The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: Participants who received at least 1 dose of study medication.
Arm/Group Title TMC278 25 mg TMC278 75 mg TMC278 150 mg All TMC278 Efavirenz
Hide Arm/Group Description:
TMC278 25 mg once daily
TMC278 75 mg once daily
TMC278 150 mg once daily
TMC278 25 mg, 75 mg, and 150 mg once daily
Efaviren 600 mg once daily
Overall Number of Participants Analyzed 93 95 91 279 89
Measure Type: Number
Unit of Measure: Participants
74 76 70 220 72
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TMC278 25 mg, TMC278 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.92
Comments The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
Method Regression, Logistic
Comments This model with factors treatment, region, and Nucleoside/tide reverse transcriptase inhibitors (N[t]RTIs) used, and baseline viral load as covariate.
Method of Estimation Estimation Parameter Differences in response rate
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-10.4 to 11.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TMC278 25 mg, TMC278 150 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.56
Comments The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
Method Regression, Logistic
Comments This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
Method of Estimation Estimation Parameter Difference in response rate
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-13.6 to 9.0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TMC278 75 mg, TMC278 150 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.62
Comments The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
Method Regression, Logistic
Comments This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
Method of Estimation Estimation Parameter Difference in response rate
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-14.0 to 8.4
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection All TMC278, Efavirenz
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.80
Comments The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
Method Regression, Logistic
Comments This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
Method of Estimation Estimation Parameter Difference in response rate
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-10.5 to 7.5
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Hide Description The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Time Frame Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: Participants who received at least 1 dose of study medication.
Arm/Group Title TMC278 25 mg TMC278 75 mg TMC278 150 mg All TMC278 Efavirenz
Hide Arm/Group Description:
TMC278 25 mg once daily
TMC278 75 mg once daily
TMC278 150 mg once daily
TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz 600 mg once daily
Overall Number of Participants Analyzed 93 95 91 279 89
Measure Type: Number
Unit of Measure: Participants
71 68 65 204 63
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TMC278 25 mg, TMC278 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.45
Comments The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
Method Regression, Logistic
Comments This model with factors treatment, region, and Nucleoside/tide reverse transcriptase inhibitors (N[t]RTIs) used, and baseline viral load as covariate.
Method of Estimation Estimation Parameter Difference in response rate
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-17.1 to 7.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TMC278 25 mg, TMC278 150 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.45
Comments The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
Method Regression, Logistic
Comments This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
Method of Estimation Estimation Parameter Difference in response rate
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-17.3 to 7.7
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TMC278 75 mg, TMC278 150 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
Method Regression, Logistic
Comments This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
Method of Estimation Estimation Parameter Difference in response rate
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-12.9 to 12.8
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection All TMC278, Efavirenz
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
Method Regression, Logistic
Comments This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
Method of Estimation Estimation Parameter Differences in response
Estimated Value 2.6
Confidence Interval (2-Sided) 95%
-8.1 to 13.3
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis
Hide Description The analysis is based on the last observed viral load data within the Week 96 window. Virologic response is defined as a viral load less than 50 copies/mL. Missing viral load was considered as non-response.
Time Frame Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: Participants who received at least 1 dose of study medication.
Arm/Group Title TMC278 25 mg TMC278 75 mg TMC278 150 mg All TMC278 Efavirenz
Hide Arm/Group Description:
TMC278 25 mg once daily
TMC278 75 mg once daily
TMC278 150 mg once daily
TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz 600 mg once daily
Overall Number of Participants Analyzed 93 95 91 279 89
Measure Type: Number
Unit of Measure: Participants
71 70 66 207 64
4.Secondary Outcome
Title Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Hide Description The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Time Frame Week 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: Participants who received at least 1 dose of study medication. This was measured at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.
Arm/Group Title All TMC278 Efavirenz
Hide Arm/Group Description:
TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz 600 mg once daily
Overall Number of Participants Analyzed 279 89
Measure Type: Number
Unit of Measure: Participants
152 51
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All TMC278, Efavirenz
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rate
Estimated Value -2.8
Confidence Interval 95%
-14.7 to 9.1
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis
Hide Description The analysis is based on the last observed viral load data within the Week 240 window. Virologic response is defined as a viral load less than 50 copies/mL. Missing viral load was considered as non-response.
Time Frame Week 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: Participants who received at least 1 dose of study medication. This was measured at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.
Arm/Group Title All TMC278 Efavirenz
Hide Arm/Group Description:
TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz 600 mg once daily
Overall Number of Participants Analyzed 279 89
Measure Type: Number
Unit of Measure: Participants
150 51
6.Secondary Outcome
Title Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 400 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Hide Description The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Time Frame Week 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: Participants who received at least 1 dose of study medication. This was measured at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.
Arm/Group Title All TMC278 Efavirenz
Hide Arm/Group Description:
TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz 600 mg once daily
Overall Number of Participants Analyzed 279 89
Measure Type: Number
Unit of Measure: Participants
166 54
7.Secondary Outcome
Title Change From Baseline in CD4+ Cell Count (Absolute) at Week 96
Hide Description Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Time Frame Baseline (Day 1 of Week 0) to Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: Participants who received at least 1 dose of study medication.Efavirenz group, 1 participant was excluded due to missing baseline CD4+ cell count.
Arm/Group Title TMC278 25mg TMC278 75 mg TMC278 150 mg All TMC278 Efavirenz
Hide Arm/Group Description:
TMC278 25 mg once daily
TMC278 75 mg once daily
TMC278 150 mg once daily
TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz 600 mg once daily
Overall Number of Participants Analyzed 93 95 91 279 88
Mean (Standard Deviation)
Unit of Measure: Cells per microliter
145.9  (117.0) 172.0  (156.5) 158.9  (156.5) 159.0  (144.4) 159.8  (125.7)
8.Secondary Outcome
Title Change From Baseline in CD4+ Cell Count (Relative) at Week 96
Hide Description Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Time Frame Baseline (Day 1 of Week 0) to Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: Participants who received at least 1 dose of study medication. Efavirenz group, 1 participant was excluded due to missing baseline CD4+ cell count.
Arm/Group Title TMC278 25mg TMC278 75 mg TMC278 150 mg All TMC278 Efavirenz
Hide Arm/Group Description:
TMC278 25 mg once daily
TMC278 75 mg once daily
TMC278 150 mg once daily
TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz 600 mg once daily
Overall Number of Participants Analyzed 93 95 91 279 88
Mean (Standard Deviation)
Unit of Measure: Percentage of CD4+ Cells
8.6  (6.9) 9.9  (7.3) 9.3  (7.1) 9.3  (7.1) 9.6  (7.0)
9.Secondary Outcome
Title Change From Baseline in CD4+ Cell Count (Absolute) at Week 240
Hide Description Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Time Frame Baseline (Day 1 of Week 0) to Week 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population: Participants who received at least 1 dose of study medication. Efavirenz group, 1 participant was excluded due to missing baseline CD4+ cell count. This was measured at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.
Arm/Group Title All TMC278 Efavirenz
Hide Arm/Group Description:
TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz 600 mg once daily
Overall Number of Participants Analyzed 279 88
Mean (Standard Deviation)
Unit of Measure: Cells per microliter
221.0  (227.2) 217.9  (213.7)
10.Secondary Outcome
Title Change From Baseline in CD4+ Cell Count (Relative) at Week 240
Hide Description Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Time Frame Baseline (Day 1 of week 0) to Week 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population: Participants who received at least 1 dose of study medication. Efavirenz group, 1 participant was excluded due to missing baseline CD4+ cell count. This was measured at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.
Arm/Group Title All TMC278 Efavirenz
Hide Arm/Group Description:
TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz 600 mg once daily
Overall Number of Participants Analyzed 279 88
Mean (Standard Deviation)
Unit of Measure: Percentage of CD4+ cells
8.7  (8.7) 9.7  (9.1)
11.Secondary Outcome
Title Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure
Hide Description Virologic failure for the resistance determinations was defined as a viral load greater than 0.5 log10 copies /mL above the nadir with a minimum of 500 copies/mL. For this study, treatment-emergent mutations (for at least one treatment) are presented as Resistance associated mutation (RAMs): i) Non-nucleotide reverse transcriptase inhibitor (NNRTI) RAMs, ii) Nucleoside/tide reverse transcriptase inhibitor (N[t]RTI RAMs).
Time Frame Week 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: Participants who received at least 1 dose of study medication. This was measured at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.
Arm/Group Title All TMC278 Efavirenz
Hide Arm/Group Description:
TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz 600 mg once daily
Overall Number of Participants Analyzed 279 89
Measure Type: Number
Unit of Measure: Participants
Treatment-emergent NNRTI RAM 17 4
E138K 7 0
K101E 6 0
K103N 1 3
Treatment-emergent N(t)RTI RAM 13 0
M184V 10 0
12.Secondary Outcome
Title Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) for TMC278
Hide Description For each participant, a single value for area under the plasma concentration-time curve from time of administration up to 24 hours post dosing (AUC24h) of TMC278 was estimated from a population pharmacokinetic model, based on all samples collected throughout the trial up to Week 96.
Time Frame Up to Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis included participants with sufficient number of pharmacokinetic samples in order to derive population pharmacokinetic parameter.
Arm/Group Title TMC278 25 mg TMC278 75 mg TMC278 150 mg
Hide Arm/Group Description:
TMC278 25 mg once daily
TMC278 75 mg once daily
TMC278 150 mg once daily
Overall Number of Participants Analyzed 89 93 87
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
2767  (1166) 5906  (2419) 10281  (4208)
13.Secondary Outcome
Title Trough Plasma Concentration (Ctrough) for TMC278
Hide Description For each participant, a single value for trough (i.e. predose) plasma concentration (Ctrough) of TMC278 was estimated from a population pharmacokinetic model, based on samples collected throughout the trial up to Week 96.
Time Frame Up to Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis included participants with sufficient number of pharnacokintetic samples in order to derive population pharmacokinetic parameter.
Arm/Group Title TMC278 25 mg TMC278 75 mg TMC278 150 mg
Hide Arm/Group Description:
TMC278 25 mg once daily
TMC278 75 mg once daily
TMC278 150 mg once daily
Overall Number of Participants Analyzed 89 93 87
Mean (Standard Deviation)
Unit of Measure: ng/mL
92.7  (45.2) 196.0  (90.1) 342.0  (154.0)
14.Secondary Outcome
Title Number of Participants With Virologic Response (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm, by Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) Quartiles
Hide Description Quartile 1, 2, 3 and 4 of AUC24h means the quartile with the lowest 25%, 26-50%, 51-75% and the highest 25% of AUC24h values, respectively, irrespective of the different doses of TMC278. For each participant, a single value for area under the plasma concentration-time curve from time of administration up to 24 hours post dosing (AUC24h) of TMC278 was estimated from a population pharmacokinetic model, based on all samples collected throughout the trial up to Week 96. Virologic response was calculated by time to loss of virologic response (TLOVR) algorithm.
Time Frame Up to Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis included participants who received TMC278 with sufficient number of pharnacokintetic samples in order to derive population pharmacokinetic parameter. Participants who discontinued treatment for reasons other than virological failure were excluded from this analysis.
Arm/Group Title AUC24h Quartile 1 AUC24h Quartile 2 AUC24h Quartile 3 AUC24h Quartile 4
Hide Arm/Group Description:
TMC278 25 mg, 75 mg, and 150 mg once daily
TMC278 25 mg, 75 mg, and 150 mg once daily
TMC278 25 mg, 75 mg, and 150 mg once daily
TMC278 25 mg, 75 mg, and 150 mg once daily
Overall Number of Participants Analyzed 58 54 59 56
Measure Type: Number
Unit of Measure: Participants
48 50 55 51
Time Frame Up to 336 weeks for participants in the TMC278 treatment group and up to 260 weeks for participants in the efavirenz treatment group.
Adverse Event Reporting Description Adverse events were reported at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.
 
Arm/Group Title All TMC278 Efavirenz
Hide Arm/Group Description TMC278 25 mg, 75 mg, and 150 mg once daily Efavirenz 600 mg once daily
All-Cause Mortality
All TMC278 Efavirenz
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
All TMC278 Efavirenz
Affected / at Risk (%) Affected / at Risk (%)
Total   49/279 (17.56%)   17/89 (19.10%) 
Blood and lymphatic system disorders     
Anaemia  1  5/279 (1.79%)  0/89 (0.00%) 
Leukopenia  1  1/279 (0.36%)  0/89 (0.00%) 
Neutropenia  1  1/279 (0.36%)  0/89 (0.00%) 
Cardiac disorders     
Acute myocardial infarction  1  1/279 (0.36%)  0/89 (0.00%) 
Angina unstable  1  1/279 (0.36%)  0/89 (0.00%) 
Supraventricular tachycardia  1  1/279 (0.36%)  0/89 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  1/279 (0.36%)  0/89 (0.00%) 
Anal fissure  1  1/279 (0.36%)  0/89 (0.00%) 
Anal fistula  1  2/279 (0.72%)  0/89 (0.00%) 
Appendicitis perforated  1  1/279 (0.36%)  0/89 (0.00%) 
Colitis  1  0/279 (0.00%)  1/89 (1.12%) 
Constipation  1  1/279 (0.36%)  0/89 (0.00%) 
Diarrhoea haemorrhagic  1  0/279 (0.00%)  1/89 (1.12%) 
Intestinal infarction  1  1/279 (0.36%)  0/89 (0.00%) 
Intestinal obstruction  1  1/279 (0.36%)  0/89 (0.00%) 
Pancreatitis  1  1/279 (0.36%)  0/89 (0.00%) 
Pancreatitis acute  1  1/279 (0.36%)  0/89 (0.00%) 
Peritonitis  1  0/279 (0.00%)  1/89 (1.12%) 
Rectal haemorrhage  1  1/279 (0.36%)  0/89 (0.00%) 
General disorders     
Chest pain  1  1/279 (0.36%)  0/89 (0.00%) 
Death  1  1/279 (0.36%)  0/89 (0.00%) 
Pyrexia  1  2/279 (0.72%)  0/89 (0.00%) 
Hepatobiliary disorders     
Bile duct stone  1  1/279 (0.36%)  0/89 (0.00%) 
Cholecystitis acute  1  1/279 (0.36%)  0/89 (0.00%) 
Cholelithiasis  1  1/279 (0.36%)  0/89 (0.00%) 
Cytolytic hepatitis  1  1/279 (0.36%)  0/89 (0.00%) 
Hepatitis  1  1/279 (0.36%)  0/89 (0.00%) 
Hepatitis acute  1  0/279 (0.00%)  1/89 (1.12%) 
Hydrocholecystis  1  1/279 (0.36%)  0/89 (0.00%) 
Infections and infestations     
Abscess neck  1  1/279 (0.36%)  0/89 (0.00%) 
Appendicitis  1  0/279 (0.00%)  1/89 (1.12%) 
Arthritis bacterial  1  1/279 (0.36%)  0/89 (0.00%) 
Cellulitis  1  0/279 (0.00%)  1/89 (1.12%) 
Clostridial infection  1  1/279 (0.36%)  1/89 (1.12%) 
Cytomegalovirus colitis  1  1/279 (0.36%)  0/89 (0.00%) 
Hepatitis C  1  0/279 (0.00%)  1/89 (1.12%) 
Implant site infection  1  1/279 (0.36%)  0/89 (0.00%) 
Lobar pneumonia  1  1/279 (0.36%)  1/89 (1.12%) 
Lung infection  1  1/279 (0.36%)  0/89 (0.00%) 
Malaria  1  0/279 (0.00%)  1/89 (1.12%) 
Meningitis tuberculous  1  1/279 (0.36%)  0/89 (0.00%) 
Oral candidiasis  1  1/279 (0.36%)  0/89 (0.00%) 
Osteomyelitis  1  1/279 (0.36%)  0/89 (0.00%) 
Perianal abscess  1  1/279 (0.36%)  0/89 (0.00%) 
Pneumonia  1  3/279 (1.08%)  0/89 (0.00%) 
Pneumonia streptococcal  1  1/279 (0.36%)  0/89 (0.00%) 
Respiratory tract infection  1  1/279 (0.36%)  0/89 (0.00%) 
Sepsis syndrome  1  1/279 (0.36%)  0/89 (0.00%) 
Septic shock  1  1/279 (0.36%)  0/89 (0.00%) 
Subcutaneous abscess  1  0/279 (0.00%)  2/89 (2.25%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  1/279 (0.36%)  0/89 (0.00%) 
Brain contusion  1  1/279 (0.36%)  0/89 (0.00%) 
Drug toxicity  1  1/279 (0.36%)  0/89 (0.00%) 
Humerus fracture  1  0/279 (0.00%)  1/89 (1.12%) 
Muscle injury  1  0/279 (0.00%)  1/89 (1.12%) 
Road traffic accident  1  1/279 (0.36%)  1/89 (1.12%) 
Investigations     
Alanine aminotransferase increased  1  1/279 (0.36%)  0/89 (0.00%) 
Aspartate aminotransferase increased  1  1/279 (0.36%)  0/89 (0.00%) 
Blood amylase increased  1  1/279 (0.36%)  1/89 (1.12%) 
Metabolism and nutrition disorders     
Anorexia  1  1/279 (0.36%)  0/89 (0.00%) 
Dehydration  1  1/279 (0.36%)  0/89 (0.00%) 
Diabetes mellitus  1  1/279 (0.36%)  0/89 (0.00%) 
Metabolic acidosis  1  1/279 (0.36%)  0/89 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/279 (0.00%)  1/89 (1.12%) 
Back pain  1  1/279 (0.36%)  0/89 (0.00%) 
Costochondritis  1  1/279 (0.36%)  0/89 (0.00%) 
Lumbar spinal stenosis  1  1/279 (0.36%)  0/89 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Burkitt's lymphoma  1  2/279 (0.72%)  0/89 (0.00%) 
Cervix cancer metastatic  1  1/279 (0.36%)  1/89 (1.12%) 
Chondrosarcoma metastatic  1  0/279 (0.00%)  1/89 (1.12%) 
Kaposi's sarcoma  1  1/279 (0.36%)  0/89 (0.00%) 
Lymphoma  1  2/279 (0.72%)  0/89 (0.00%) 
Squamous cell carcinoma  1  1/279 (0.36%)  0/89 (0.00%) 
Uterine leiomyoma  1  1/279 (0.36%)  0/89 (0.00%) 
Nervous system disorders     
Epilepsy  1  1/279 (0.36%)  0/89 (0.00%) 
Headache  1  0/279 (0.00%)  1/89 (1.12%) 
Pregnancy, puerperium and perinatal conditions     
Pregnancy  1  0/279 (0.00%)  1/89 (1.12%) 
Psychiatric disorders     
Depression  1  1/279 (0.36%)  0/89 (0.00%) 
Intentional self-injury  1  1/279 (0.36%)  0/89 (0.00%) 
Major depression  1  1/279 (0.36%)  0/89 (0.00%) 
Suicide attempt  1  1/279 (0.36%)  0/89 (0.00%) 
Renal and urinary disorders     
Renal failure  1  1/279 (0.36%)  0/89 (0.00%) 
Renal impairment  1  1/279 (0.36%)  0/89 (0.00%) 
Reproductive system and breast disorders     
Ovarian cyst  1  1/279 (0.36%)  0/89 (0.00%) 
Prostatitis  1  0/279 (0.00%)  1/89 (1.12%) 
Respiratory, thoracic and mediastinal disorders     
Alveolitis allergic  1  1/279 (0.36%)  0/89 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash maculo-papular  1  1/279 (0.36%)  0/89 (0.00%) 
Surgical and medical procedures     
Ovarian cystectomy  1  1/279 (0.36%)  0/89 (0.00%) 
Penile prosthesis insertion  1  1/279 (0.36%)  0/89 (0.00%) 
Vascular disorders     
Arterial occlusive disease  1  1/279 (0.36%)  0/89 (0.00%) 
Deep vein thrombosis  1  0/279 (0.00%)  1/89 (1.12%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All TMC278 Efavirenz
Affected / at Risk (%) Affected / at Risk (%)
Total   241/279 (86.38%)   82/89 (92.13%) 
Blood and lymphatic system disorders     
Anaemia  1  24/279 (8.60%)  2/89 (2.25%) 
Ear and labyrinth disorders     
Vertigo  1  4/279 (1.43%)  10/89 (11.24%) 
Eye disorders     
Conjunctivitis  1  9/279 (3.23%)  5/89 (5.62%) 
Gastrointestinal disorders     
Abdominal pain  1  20/279 (7.17%)  4/89 (4.49%) 
Abdominal pain upper  1  13/279 (4.66%)  5/89 (5.62%) 
Diarrhoea  1  33/279 (11.83%)  16/89 (17.98%) 
Dyspepsia  1  36/279 (12.90%)  7/89 (7.87%) 
Haemorrhoids  1  10/279 (3.58%)  7/89 (7.87%) 
Nausea  1  100/279 (35.84%)  26/89 (29.21%) 
Vomiting  1  33/279 (11.83%)  11/89 (12.36%) 
General disorders     
Fatigue  1  23/279 (8.24%)  4/89 (4.49%) 
Pyrexia  1  19/279 (6.81%)  3/89 (3.37%) 
Infections and infestations     
Body tinea  1  4/279 (1.43%)  7/89 (7.87%) 
Bronchitis  1  20/279 (7.17%)  3/89 (3.37%) 
Condyloma acuminatum  1  17/279 (6.09%)  3/89 (3.37%) 
Gastroenteritis  1  11/279 (3.94%)  5/89 (5.62%) 
Herpes simplex  1  25/279 (8.96%)  7/89 (7.87%) 
Herpes zoster  1  15/279 (5.38%)  4/89 (4.49%) 
Influenza  1  27/279 (9.68%)  8/89 (8.99%) 
Nasopharyngitis  1  45/279 (16.13%)  19/89 (21.35%) 
Pharyngitis  1  18/279 (6.45%)  4/89 (4.49%) 
Respiratory tract infection  1  9/279 (3.23%)  5/89 (5.62%) 
Respiratory tract infection viral  1  1/279 (0.36%)  7/89 (7.87%) 
Rhinitis  1  12/279 (4.30%)  5/89 (5.62%) 
Sinusitis  1  20/279 (7.17%)  3/89 (3.37%) 
Tinea pedis  1  8/279 (2.87%)  5/89 (5.62%) 
Upper respiratory tract infection  1  49/279 (17.56%)  9/89 (10.11%) 
Urinary tract infection  1  21/279 (7.53%)  6/89 (6.74%) 
Investigations     
Alanine aminotransferase increased  1  21/279 (7.53%)  6/89 (6.74%) 
Aspartate aminotransferase increased  1  17/279 (6.09%)  5/89 (5.62%) 
Blood cholesterol increased  1  13/279 (4.66%)  11/89 (12.36%) 
Low density lipoprotein increased  1  16/279 (5.73%)  9/89 (10.11%) 
Metabolism and nutrition disorders     
Anorexia  1  19/279 (6.81%)  7/89 (7.87%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  39/279 (13.98%)  11/89 (12.36%) 
Back pain  1  31/279 (11.11%)  5/89 (5.62%) 
Myalgia  1  18/279 (6.45%)  3/89 (3.37%) 
Nervous system disorders     
Dizziness  1  31/279 (11.11%)  27/89 (30.34%) 
Headache  1  62/279 (22.22%)  15/89 (16.85%) 
Somnolence  1  10/279 (3.58%)  10/89 (11.24%) 
Psychiatric disorders     
Abnormal dreams  1  6/279 (2.15%)  5/89 (5.62%) 
Depression  1  19/279 (6.81%)  9/89 (10.11%) 
Insomnia  1  23/279 (8.24%)  6/89 (6.74%) 
Nightmare  1  1/279 (0.36%)  5/89 (5.62%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  29/279 (10.39%)  12/89 (13.48%) 
Skin and subcutaneous tissue disorders     
Dry skin  1  14/279 (5.02%)  1/89 (1.12%) 
Pruritus  1  18/279 (6.45%)  4/89 (4.49%) 
Rash  1  5/279 (1.79%)  7/89 (7.87%) 
Seborrhoeic dermatitis  1  7/279 (2.51%)  5/89 (5.62%) 
Vascular disorders     
Hypertension  1  22/279 (7.89%)  3/89 (3.37%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
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.
Results Point of Contact
Name/Title: Director
Organization: Janssen-Virco BE
Phone: 32 14 641418
Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00110305     History of Changes
Obsolete Identifiers: NCT00980837
Other Study ID Numbers: CR006760
TMC278-C204 ( Other Identifier: Tibotec Pharmaceuticals, Ireland )
R278474-C204 ( Other Identifier: Tibotec Pharmaceuticals, Ireland )
First Submitted: May 5, 2005
First Posted: May 6, 2005
Results First Submitted: April 26, 2013
Results First Posted: October 28, 2013
Last Update Posted: June 25, 2014