TMC278-TiDP6-C209: A Clinical Trial in Treatment Naive HIV-1 Patients Comparing TMC278 to Efavirenz in Combination With Tenofovir + Emtricitabine.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00540449
First received: October 4, 2007
Last updated: May 29, 2015
Last verified: May 2015
Results First Received: June 14, 2011  
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
Conditions: HIV Infections
HIV-1
Human Immunodeficiency Virus Type 1
Interventions: Drug: TMC278
Drug: Efavirenz

  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
One hundred and twelve sites in 21 countries randomized participants. In total, 694 participants were randomized: four participants did not start treatment and 690 participants started treatment (346 in the TMC278 group and 344 in the efavirenz [control ] group).

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

Reporting Groups
  Description
TMC278 25 milligram (mg) tablet once daily for 96 weeks.
Efavirenz 600 mg once daily for 96 weeks.

Participant Flow:   Overall Study
    TMC278     Efavirenz  
STARTED     346     344  
COMPLETED     262     266  
NOT COMPLETED     84     78  
Adverse Event                 12                 32  
Sponsor's Decision                 1                 1  
Subject Ineligible To Continue The Trial                 2                 1  
Lost to Follow-up                 19                 17  
Subject Non-Compliant                 7                 5  
Subject Reached A Virologic Endpoint                 32                 8  
Withdrawal by Subject                 10                 10  
Not specified                 1                 4  



  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.
The analysis population included intent to treat (ITT) population defined as all randomized participants who received at least one dose of the study medication.

Reporting Groups
  Description
TMC278 25 milligram (mg) tablet once daily for 96 weeks.
Efavirenz 600 mg once daily for 96 weeks.
Total Total of all reporting groups

Baseline Measures
    TMC278     Efavirenz     Total  
Number of Participants  
[units: participants]
  346     344     690  
Age  
[units: participants]
     
<=18 years     1     0     1  
Between 18 and 65 years     343     343     686  
>=65 years     2     1     3  
Age  
[units: years]
Mean (Standard Deviation)
  37  (9.68)     36.7  (9.51)     36.8  (9.59)  
Gender  
[units: participants]
     
Female     78     69     147  
Male     268     275     543  
Region Enroll  
[units: participants]
     
Africa     32     31     63  
Asia     47     51     98  
Latin America     60     69     129  
USA, Canada, Europe, Australia     207     193     400  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48   [ Time Frame: Week 48 ]

2.  Secondary:   The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48   [ Time Frame: Week 48 ]
  Hide Outcome Measure 2

Measure Type Secondary
Measure Title The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48
Measure Description The analysis is based on the last observed viral load (VL) data within the Week 48 window. Virologic response is defined as a VL<50 copies/ml (observed case). Missing VL was considered as non-response. Virologic Failure includes subjects who had VL>=50 copies/ml in the Wk48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a VL>=50 copies/ml and subjects who had a switch in background regimen that was not permitted by the protocol.
Time Frame Week 48  
Safety Issue No  

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

Reporting Groups
  Description
TMC278 25 milligram (mg) tablet once daily for 96 weeks.
Efavirenz 600 mg once daily for 96 weeks.

Measured Values
    TMC278     Efavirenz  
Number of Participants Analyzed  
[units: participants]
  346     344  
The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48  
[units: Participants]
   
Virologic Response HIV RNA <50 copies/mL at Wk 48     285     281  
Virologic Failure     47     24  
No Viral Load Data in 48 week window     14     39  


Statistical Analysis 1 for The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Regression, Logistic
P Value [4] <0.0001
Difference in proportion of response [5] 0.3
95% Confidence Interval -5.4 to 5.9
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  If the lower limit of the 95% 2-sided confidence interval of the difference in proportions (TMC278 – EFV) exceeds -12%, non-inferiority of TMC278 versus EFV can be concluded.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Logistic regression model included treatment arm as factor and baseline (log10) viral load as covariate.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  Difference in proportion responders was estimated through the logistic regression model.



3.  Secondary:   Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96   [ Time Frame: Week 96 ]

4.  Secondary:   The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96   [ Time Frame: Week 96 ]

5.  Secondary:   Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Post-Week 96 Visit.   [ Time Frame: Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz ]

6.  Secondary:   Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48   [ Time Frame: Week 48 ]

7.  Secondary:   Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96   [ Time Frame: Week 96 ]

8.  Secondary:   Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data)   [ Time Frame: Week 48, Week 96 ]

9.  Secondary:   Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure   [ Time Frame: 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
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Leader
Organization: Janssen Infectious Diseases BVBA
e-mail: ClinicalTrialDisclosure@its.jnj.com


No publications provided by Tibotec Pharmaceuticals, Ireland

Publications automatically indexed to this study:

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00540449     History of Changes
Obsolete Identifiers: NCT00613639
Other Study ID Numbers: CR002689, TMC278-TIDP6-C209
Study First Received: October 4, 2007
Results First Received: June 14, 2011
Last Updated: May 29, 2015
Health Authority: United States: Food and Drug Administration
Ireland: Irish Agriculture and Food Development Authority
Canada: Health Canada
Great Britain: Medicines and Healthcare Products Regulatory Agency
Taiwan: Department of Health
Great Britain: Research Ethics Committee