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A Study to Determine the Safety and Efficacy of Once Daily Raltegravir Compared to Twice Daily Raltegravir (MK-0518-071)

This study has been terminated.
(Primary efficacy analysis at Week 48 did not demonstrate non-inferiority of raltegravir 800 mg once daily versus raltegravir 400 mg twice daily)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00745823
First received: September 2, 2008
Last updated: October 1, 2015
Last verified: October 2015
Results First Received: March 6, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: HIV
Interventions: Drug: Comparator: Raltegravir 400 mg b.i.d.
Drug: Experimental: Raltegravir 800 mg q.d.
Drug: TRUVADA™

  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
No text entered.

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
Raltegravir 800 mg q.d. Raltegravir 800 mg by mouth (PO) once daily (q.d.) plus placebo to raltegravir PO twice daily (b.i.d.) plus one tablet of TRUVADA™ for 96 weeks
Raltegravir 400 mg b.i.d. Raltegravir 400 mg PO b.i.d. plus placebo to raltegravir PO q.d. plus one tablet of TRUVADA™ for 96 weeks

Participant Flow:   Overall Study
    Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d.
STARTED   386   389 
TREATED Week 0 - 96   382   388 
COMPLETED   1   3 
NOT COMPLETED   385   386 
Adverse Event                5                3 
Lack of Efficacy                20                6 
Lost to Follow-up                10                11 
Physician Decision                10                5 
Pregnancy                0                4 
Withdrawal by Subject                14                8 
Study Terminated by Sponsor                326                349 



  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
Raltegravir 800 mg q.d. Raltegravir 800 mg by mouth (PO) once daily (q.d.) plus placebo to raltegravir PO twice daily (b.i.d.) plus one tablet of TRUVADA™ for 96 weeks
Raltegravir 400 mg b.i.d. Raltegravir 400 mg PO b.i.d. plus placebo to raltegravir PO q.d. plus one tablet of TRUVADA™ for 96 weeks
Total Total of all reporting groups

Baseline Measures
   Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d.   Total 
Overall Participants Analyzed 
[Units: Participants]
 386   389   775 
Age, Customized 
[Units: Participants]
     
Between 18 and 64 years   382   382   764 
>=64 years   4   7   11 
Gender 
[Units: Participants]
     
Female   68   90   158 
Male   318   299   617 


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks   [ Time Frame: Week 48 ]

Measure Type Primary
Measure Title Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks
Measure Description No text entered.
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.
Data were analyzed for all participants treated with study drug. Participants who did not complete the study were treated as treatment failures.

Reporting Groups
  Description
Raltegravir 800 mg q.d. Raltegravir 800 mg by mouth (PO) once daily (q.d.) plus placebo to raltegravir PO twice daily (b.i.d.) plus one tablet of TRUVADA™ for 96 weeks
Raltegravir 400 mg b.i.d. Raltegravir 400 mg PO b.i.d. plus placebo to raltegravir PO q.d. plus one tablet of TRUVADA™ for 96 weeks

Measured Values
   Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d. 
Participants Analyzed 
[Units: Participants]
 382   386 
Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks 
[Units: Participants]
 318   343 


Statistical Analysis 1 for Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Miettinen and Nurminen
P Value [4] 0.044
Mean Difference (Final Values) [5] -5.7
95% Confidence Interval -10.7 to -0.83
[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:
  The 800 mg q.d. dosage was considered non-inferior to 400 mg b.i.d. if the lower bound of the 2-sided exact 95% CI for difference in response rate remained above -10%.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[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:
  No text entered.



2.  Primary:   Number of Participants With One or More Adverse Events at 48 Weeks   [ Time Frame: Week 48 ]

Measure Type Primary
Measure Title Number of Participants With One or More Adverse Events at 48 Weeks
Measure Description No text entered.
Time Frame Week 48  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data were analyzed for all randomized participants who received at least one dose of study drug.

Reporting Groups
  Description
Raltegravir 800 mg q.d. Raltegravir 800 mg by mouth (PO) once daily (q.d.) plus placebo to raltegravir PO twice daily (b.i.d.) plus one tablet of TRUVADA™ for 96 weeks
Raltegravir 400 mg b.i.d. Raltegravir 400 mg PO b.i.d. plus placebo to raltegravir PO q.d. plus one tablet of TRUVADA™ for 96 weeks

Measured Values
   Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d. 
Participants Analyzed 
[Units: Participants]
 382   388 
Number of Participants With One or More Adverse Events at 48 Weeks 
[Units: Participants]
 331   337 


Statistical Analysis 1 for Number of Participants With One or More Adverse Events at 48 Weeks
Groups [1] All groups
Method [2] Miettinen and Nurminen
Mean Difference (Final Values) [3] -0.2
95% Confidence Interval -5.0 to 4.6
[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:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



3.  Primary:   Number of Participants Who Discontinued Due to an Adverse Event at 48 Weeks   [ Time Frame: Week 48 ]

Measure Type Primary
Measure Title Number of Participants Who Discontinued Due to an Adverse Event at 48 Weeks
Measure Description No text entered.
Time Frame Week 48  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data were analyzed for all randomized participants who received at least one dose of study drug.

Reporting Groups
  Description
Raltegravir 800 mg q.d. Raltegravir 800 mg by mouth (PO) once daily (q.d.) plus placebo to raltegravir PO twice daily (b.i.d.) plus one tablet of TRUVADA™ for 96 weeks
Raltegravir 400 mg b.i.d. Raltegravir 400 mg PO b.i.d. plus placebo to raltegravir PO q.d. plus one tablet of TRUVADA™ for 96 weeks

Measured Values
   Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d. 
Participants Analyzed 
[Units: Participants]
 382   388 
Number of Participants Who Discontinued Due to an Adverse Event at 48 Weeks 
[Units: Participants]
 4   3 


Statistical Analysis 1 for Number of Participants Who Discontinued Due to an Adverse Event at 48 Weeks
Groups [1] All groups
Mean Difference (Final Values) [2] 0.3
95% Confidence Interval -1.3 to 2.0
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



4.  Secondary:   Number of Participants With HIV Ribonucleic Acid (RNA) <400 Copies/mL at 48 Weeks   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Number of Participants With HIV Ribonucleic Acid (RNA) <400 Copies/mL at 48 Weeks
Measure Description No text entered.
Time Frame 48 weeks  
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.
Data were analyzed for all participants treated with study drug. Participants who did not complete the study were treated as treatment failures.

Reporting Groups
  Description
Raltegravir 800 mg q.d. Raltegravir 800 mg by mouth (PO) once daily (q.d.) plus placebo to raltegravir PO twice daily (b.i.d.) plus one tablet of TRUVADA™ for 96 weeks
Raltegravir 400 mg b.i.d. Raltegravir 400 mg PO b.i.d. plus placebo to raltegravir PO q.d. plus one tablet of TRUVADA™ for 96 weeks

Measured Values
   Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d. 
Participants Analyzed 
[Units: Participants]
 382   386 
Number of Participants With HIV Ribonucleic Acid (RNA) <400 Copies/mL at 48 Weeks 
[Units: Participants]
 338   361 


Statistical Analysis 1 for Number of Participants With HIV Ribonucleic Acid (RNA) <400 Copies/mL at 48 Weeks
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Miettinen and Nurminen
P Value [4] 0.011
Mean Difference (Final Values) [5] -5.1
95% Confidence Interval -9.29 to -1.06
[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:
  The 800 mg q.d. dosage was considered non-inferior to 400 mg b.i.d. if the lower bound of the 2-sided exact 95% CI for difference in response rate remained above -10%.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[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:
  No text entered.



5.  Secondary:   Mean Change From Baseline to Week 48 in CD4 Cell Count   [ Time Frame: Baseline and Week 48 ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Week 48 in CD4 Cell Count
Measure Description No text entered.
Time Frame Baseline and 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.
Data were analyzed for all participants treated with study drug. Baseline values were carried forward for participants who discontinued treatment due to lack of efficacy.

Reporting Groups
  Description
Raltegravir 800 mg q.d. Raltegravir 800 mg by mouth (PO) once daily (q.d.) plus placebo to raltegravir PO twice daily (b.i.d.) plus one tablet of TRUVADA™ for 96 weeks
Raltegravir 400 mg b.i.d. Raltegravir 400 mg PO b.i.d. plus placebo to raltegravir PO q.d. plus one tablet of TRUVADA™ for 96 weeks

Measured Values
   Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d. 
Participants Analyzed 
[Units: Participants]
 382   386 
Mean Change From Baseline to Week 48 in CD4 Cell Count 
[Units: Cells/mm^3]
Mean (95% Confidence Interval)
 209.76 
 (194.6 to 224.9) 
 196.20 
 (181.8 to 210.6) 


Statistical Analysis 1 for Mean Change From Baseline to Week 48 in CD4 Cell Count
Groups [1] All groups
Method [2] t-test, 2 sided
Mean Difference (Net) [3] 13.56
95% Confidence Interval -7.29 to 34.40
[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:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



6.  Secondary:   Number of Participants With HIV RNA <50 Copies/mL at 96 Weeks   [ Time Frame: Week 96 ]

Measure Type Secondary
Measure Title Number of Participants With HIV RNA <50 Copies/mL at 96 Weeks
Measure Description As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
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.
The Week 96 data analysis was not performed.

Reporting Groups
  Description
Raltegravir 800 mg q.d. Raltegravir 800 mg by mouth (PO) once daily (q.d.) plus placebo to raltegravir PO twice daily (b.i.d.) plus one tablet of TRUVADA™ for 96 weeks
Raltegravir 400 mg b.i.d. Raltegravir 400 mg PO b.i.d. plus placebo to raltegravir PO q.d. plus one tablet of TRUVADA™ for 96 weeks

Measured Values
   Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d. 
Participants Analyzed 
[Units: Participants]
 0   0 
Number of Participants With HIV RNA <50 Copies/mL at 96 Weeks       

No statistical analysis provided for Number of Participants With HIV RNA <50 Copies/mL at 96 Weeks



7.  Secondary:   Number of Participants With HIV RNA <400 Copies/mL at 96 Weeks   [ Time Frame: Week 96 ]

Measure Type Secondary
Measure Title Number of Participants With HIV RNA <400 Copies/mL at 96 Weeks
Measure Description As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
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.
The Week 96 data analysis was not performed.

Reporting Groups
  Description
Raltegravir 800 mg q.d. Raltegravir 800 mg by mouth (PO) once daily (q.d.) plus placebo to raltegravir PO twice daily (b.i.d.) plus one tablet of TRUVADA™ for 96 weeks
Raltegravir 400 mg b.i.d. Raltegravir 400 mg PO b.i.d. plus placebo to raltegravir PO q.d. plus one tablet of TRUVADA™ for 96 weeks

Measured Values
   Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d. 
Participants Analyzed 
[Units: Participants]
 0   0 
Number of Participants With HIV RNA <400 Copies/mL at 96 Weeks       

No statistical analysis provided for Number of Participants With HIV RNA <400 Copies/mL at 96 Weeks



8.  Secondary:   Mean Change From Baseline to Week 96 in CD4 Cell Count   [ Time Frame: Baseline and Week 96 ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Week 96 in CD4 Cell Count
Measure Description As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Time Frame Baseline and 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.
The Week 96 data analysis was not performed.

Reporting Groups
  Description
Raltegravir 800 mg q.d. Raltegravir 800 mg PO q.d. plus placebo to raltegravir PO b.i.d. plus one tablet of TRUVADA™ for 96 weeks
Raltegravir 400 mg b.i.d. Raltegravir 400 mg b.i.d. administered with TRUVADA™

Measured Values
   Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d. 
Participants Analyzed 
[Units: Participants]
 0   0 
Mean Change From Baseline to Week 96 in CD4 Cell Count       

No statistical analysis provided for Mean Change From Baseline to Week 96 in CD4 Cell Count



9.  Secondary:   Number of Participants With One or More Adverse Events at 96 Weeks   [ Time Frame: Week 96 ]

Measure Type Secondary
Measure Title Number of Participants With One or More Adverse Events at 96 Weeks
Measure Description As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Time Frame Week 96  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Raltegravir 800 mg q.d. Raltegravir 800 mg by mouth (PO) once daily (q.d.) plus placebo to raltegravir PO twice daily (b.i.d.) plus one tablet of TRUVADA™ for 96 weeks
Raltegravir 400 mg b.i.d. Raltegravir 400 mg PO b.i.d. plus placebo to raltegravir PO q.d. plus one tablet of TRUVADA™ for 96 weeks

Measured Values
   Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d. 
Participants Analyzed 
[Units: Participants]
 0   0 
Number of Participants With One or More Adverse Events at 96 Weeks       

No statistical analysis provided for Number of Participants With One or More Adverse Events at 96 Weeks



10.  Secondary:   Number of Participants Who Discontinued Due to an Adverse Event at 96 Weeks   [ Time Frame: Week 96 ]

Measure Type Secondary
Measure Title Number of Participants Who Discontinued Due to an Adverse Event at 96 Weeks
Measure Description As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Time Frame Week 96  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Raltegravir 800 mg q.d. Raltegravir 800 mg by mouth (PO) once daily (q.d.) plus placebo to raltegravir PO twice daily (b.i.d.) plus one tablet of TRUVADA™ for 96 weeks
Raltegravir 400 mg b.i.d. Raltegravir 400 mg PO b.i.d. plus placebo to raltegravir PO q.d. plus one tablet of TRUVADA™ for 96 weeks

Measured Values
   Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d. 
Participants Analyzed 
[Units: Participants]
 0   0 
Number of Participants Who Discontinued Due to an Adverse Event at 96 Weeks       

No statistical analysis provided for Number of Participants Who Discontinued Due to an Adverse Event at 96 Weeks




  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
The study was terminated before the 96-week efficacy analysis. Adverse event data were collected for the entire treatment period up to a maximum of Week 108, which defines the Overall Study period.


  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: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp
phone: 1- 800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00745823     History of Changes
Other Study ID Numbers: 0518-071
2008_543 ( Other Identifier: Merck Registration Number )
CTRI/2009/091/000145 ( Registry Identifier: CTRI )
Study First Received: September 2, 2008
Results First Received: March 6, 2012
Last Updated: October 1, 2015
Health Authority: United States: Food and Drug Administration