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;   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 
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
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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 ]

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
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Time Frame Overall Study
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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

Other Adverse Events
    Raltegravir 800 mg q.d.   Raltegravir 400 mg b.i.d.
Total, Other (not including serious) Adverse Events     
# participants affected / at risk   287/382 (75.13%)   282/388 (72.68%) 
Blood and lymphatic system disorders     
Lymphadenopathy † 1     
# participants affected / at risk   22/382 (5.76%)   21/388 (5.41%) 
# events   23   23 
Gastrointestinal disorders     
Abdominal pain † 1     
# participants affected / at risk   13/382 (3.40%)   21/388 (5.41%) 
# events   14   27 
Diarrhoea † 1     
# participants affected / at risk   70/382 (18.32%)   70/388 (18.04%) 
# events   81   87 
Nausea † 1     
# participants affected / at risk   41/382 (10.73%)   54/388 (13.92%) 
# events   47   57 
Vomiting † 1     
# participants affected / at risk   24/382 (6.28%)   25/388 (6.44%) 
# events   29   36 
General disorders     
Fatigue † 1     
# participants affected / at risk   25/382 (6.54%)   27/388 (6.96%) 
# events   28   30 
Pyrexia † 1     
# participants affected / at risk   19/382 (4.97%)   26/388 (6.70%) 
# events   23   35 
Infections and infestations     
Bronchitis † 1     
# participants affected / at risk   31/382 (8.12%)   28/388 (7.22%) 
# events   32   34 
Gastroenteritis † 1     
# participants affected / at risk   21/382 (5.50%)   14/388 (3.61%) 
# events   23   18 
Influenza † 1     
# participants affected / at risk   25/382 (6.54%)   36/388 (9.28%) 
# events   28   40 
Nasopharyngitis † 1     
# participants affected / at risk   40/382 (10.47%)   54/388 (13.92%) 
# events   51   70 
Sinusitis † 1     
# participants affected / at risk   16/382 (4.19%)   30/388 (7.73%) 
# events   17   36 
Upper respiratory tract infection † 1     
# participants affected / at risk   49/382 (12.83%)   54/388 (13.92%) 
# events   64   70 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1     
# participants affected / at risk   19/382 (4.97%)   25/388 (6.44%) 
# events   22   32 
Back pain † 1     
# participants affected / at risk   23/382 (6.02%)   22/388 (5.67%) 
# events   28   25 
Nervous system disorders     
Dizziness † 1     
# participants affected / at risk   36/382 (9.42%)   29/388 (7.47%) 
# events   39   35 
Headache † 1     
# participants affected / at risk   58/382 (15.18%)   62/388 (15.98%) 
# events   70   87 
Psychiatric disorders     
Depression † 1     
# participants affected / at risk   22/382 (5.76%)   23/388 (5.93%) 
# events   22   25 
Insomnia † 1     
# participants affected / at risk   18/382 (4.71%)   22/388 (5.67%) 
# events   18   22 
Respiratory, thoracic and mediastinal disorders     
Cough † 1     
# participants affected / at risk   38/382 (9.95%)   30/388 (7.73%) 
# events   40   41 
Oropharyngeal pain † 1     
# participants affected / at risk   15/382 (3.93%)   20/388 (5.15%) 
# events   19   23 
Skin and subcutaneous tissue disorders     
Rash † 1     
# participants affected / at risk   23/382 (6.02%)   23/388 (5.93%) 
# events   26   27 
Vascular disorders     
Hypertension † 1     
# participants affected / at risk   11/382 (2.88%)   22/388 (5.67%) 
# events   11   22 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 14.0



  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: 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