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: May 14, 2012
Last verified: May 2012
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
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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
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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  
Number of Participants  
[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
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1.  Primary:   Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks   [ Time Frame: Week 48 ]

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

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

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

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

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

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

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

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


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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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: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp
phone: 1- 800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com


No publications provided by Merck Sharp & Dohme Corp.

Publications automatically indexed to this study:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00745823     History of Changes
Other Study ID Numbers: MK-0518-071, 2008_543
Study First Received: September 2, 2008
Results First Received: March 6, 2012
Last Updated: May 14, 2012
Health Authority: United States: Food and Drug Administration