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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00110305
First received: May 5, 2005
Last updated: June 11, 2014
Last verified: June 2014
Results First Received: April 26, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, 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)

  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
368 participants were enrolled at multiple centers in different countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
All TMC278 TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz Efavirenz 600 mg once daily

Participant Flow:   Overall Study
    All TMC278     Efavirenz  
STARTED     279     89  
COMPLETED     165     57  
NOT COMPLETED     114     32  
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  
Unspecified                 8                 2  



  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
TMC278 25 mg TMC278 25 mg once daily
TMC278 75 mg TMC278 75 mg once daily
TMC 150 mg TMC278 150 mg once daily
Efavirenz Efavirenz 600 mg once daily
Total Total of all reporting groups

Baseline Measures
    TMC278 25 mg     TMC278 75 mg     TMC 150 mg     Efavirenz     Total  
Number of Participants  
[units: participants]
  93     95     91     89     368  
Age  
[units: participants]
         
<=18 years     0     0     0     0     0  
Between 18 and 65 years     92     95     89     89     365  
>=65 years     1     0     2     0     3  
Age  
[units: years]
Mean ± Standard Deviation
  36.7  ± 8.9     36.3  ± 8.3     35.9  ± 9.7     35.4  ± 8.1     36.1  ± 8.75  
Gender  
[units: participants]
         
Female     28     31     33     29     121  
Male     65     64     58     60     247  
Region Enroll  
[units: 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  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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   [ Time Frame: Week 48 ]

2.  Secondary:   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   [ Time Frame: Week 96 ]
  Hide Outcome Measure 2

Measure Type Secondary
Measure 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
Measure 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  
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.
Intent to treat population: Participants who received at least 1 dose of study medication.

Reporting Groups
  Description
TMC278 25 mg TMC278 25 mg once daily
TMC278 75 mg TMC278 75 mg once daily
TMC278 150 mg TMC278 150 mg once daily
All TMC278 TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz Efavirenz 600 mg once daily

Measured Values
    TMC278 25 mg     TMC278 75 mg     TMC278 150 mg     All TMC278     Efavirenz  
Number of Participants Analyzed  
[units: participants]
  93     95     91     279     89  
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  
[units: Participants]
  71     68     65     204     63  


Statistical Analysis 1 for 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
Groups [1] TMC278 25 mg vs. TMC278 75 mg
Method [2] Regression, Logistic
P Value [3] 0.45
Difference in response rate [4] -4.8
95% Confidence Interval ( -17.1 to 7.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  This model with factors treatment, region, and Nucleoside/tide reverse transcriptase inhibitors (N[t]RTIs) used, and baseline viral load as covariate.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for 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
Groups [1] TMC278 25 mg vs. TMC278 150 mg
Method [2] Regression, Logistic
P Value [3] 0.45
Difference in response rate [4] -4.8
95% Confidence Interval ( -17.3 to 7.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for 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
Groups [1] TMC278 75 mg vs. TMC278 150 mg
Method [2] Regression, Logistic
P Value [3] 0.99
Difference in response rate [4] 0.0
95% Confidence Interval ( -12.9 to 12.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for 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
Groups [1] All TMC278 vs. Efavirenz
Method [2] Regression, Logistic
P Value [3] 0.63
Differences in response [4] 2.6
95% Confidence Interval ( -8.1 to 13.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis   [ Time Frame: Week 96 ]

4.  Secondary:   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   [ Time Frame: Week 240 ]

5.  Secondary:   Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis   [ Time Frame: Week 240 ]

6.  Secondary:   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   [ Time Frame: Week 240 ]

7.  Secondary:   Change From Baseline in CD4+ Cell Count (Absolute) at Week 96   [ Time Frame: Baseline (Day 1 of Week 0) to Week 96 ]

8.  Secondary:   Change From Baseline in CD4+ Cell Count (Relative) at Week 96   [ Time Frame: Baseline (Day 1 of Week 0) to Week 96 ]

9.  Secondary:   Change From Baseline in CD4+ Cell Count (Absolute) at Week 240   [ Time Frame: Baseline (Day 1 of Week 0) to Week 240 ]

10.  Secondary:   Change From Baseline in CD4+ Cell Count (Relative) at Week 240   [ Time Frame: Baseline (Day 1 of week 0) to Week 240 ]

11.  Secondary:   Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure   [ Time Frame: Week 240 ]

12.  Secondary:   Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) for TMC278   [ Time Frame: Up to Week 96 ]

13.  Secondary:   Trough Plasma Concentration (Ctrough) for TMC278   [ Time Frame: Up to Week 96 ]

14.  Secondary:   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   [ Time Frame: Up to Week 96 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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.


  More Information