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
  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  
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
  Show All Outcome Measures

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
  Hide Serious Adverse Events

Time Frame Overall Study
Additional Description 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

Serious Adverse Events
    Raltegravir 800 mg q.d.     Raltegravir 400 mg b.i.d.  
Total, serious adverse events      
# participants affected / at risk     29/382 (7.59%)     46/388 (11.86%)  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Lymphadenitis † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Lymphadenopathy † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Retroperitoneal lymphadenopathy † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Thrombocytopenia † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Cardiac disorders      
Atrial fibrillation † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Pericarditis † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Gastrointestinal disorders      
Anal fistula † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Diarrhoea † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Inguinal hernia † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Proctalgia † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Vomiting † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
General disorders      
Chest pain † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Pyrexia † 1    
# participants affected / at risk     0/382 (0.00%)     4/388 (1.03%)  
# events     0     4  
Hepatobiliary disorders      
Cholecystitis acute † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Cholecystitis chronic † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Cholelithiasis † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Hepatitis † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Immune system disorders      
Immune reconstitution syndrome † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Infections and infestations      
Abscess intestinal † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Abscess jaw † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Anogenital warts † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Appendicitis † 1    
# participants affected / at risk     2/382 (0.52%)     1/388 (0.26%)  
# events     2     1  
Cytomegalovirus infection † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Diarrhoea infectious † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Eye infection syphilitic † 1    
# participants affected / at risk     1/382 (0.26%)     1/388 (0.26%)  
# events     1     1  
Gastroenteritis † 1    
# participants affected / at risk     0/382 (0.00%)     2/388 (0.52%)  
# events     0     2  
Histoplasmosis † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Meningitis aseptic † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Meningitis cryptococcal † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     2     0  
Meningitis viral † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Mycobacterium avium complex infection † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Orchitis † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Perirectal abscess † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Pneumonia † 1    
# participants affected / at risk     1/382 (0.26%)     1/388 (0.26%)  
# events     1     1  
Pneumonia pneumococcal † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Post procedural pneumonia † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Sepsis † 1    
# participants affected / at risk     0/382 (0.00%)     2/388 (0.52%)  
# events     0     2  
Shigella infection † 1    
# participants affected / at risk     1/382 (0.26%)     1/388 (0.26%)  
# events     1     1  
Injury, poisoning and procedural complications      
Forearm fracture † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Meniscus lesion † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Multiple drug overdose † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Muscle injury † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Penis injury † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Tibia fracture † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Wrist fracture † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Metabolism and nutrition disorders      
Obesity † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Anal cancer stage 0 † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Basal cell carcinoma † 1    
# participants affected / at risk     0/382 (0.00%)     2/388 (0.52%)  
# events     0     2  
Bowen's disease † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Burkitt's lymphoma † 1    
# participants affected / at risk     0/382 (0.00%)     2/388 (0.52%)  
# events     0     2  
Colon cancer † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Hodgkin's disease † 1    
# participants affected / at risk     0/382 (0.00%)     2/388 (0.52%)  
# events     0     2  
Kaposi's sarcoma AIDS related † 1    
# participants affected / at risk     3/382 (0.79%)     3/388 (0.77%)  
# events     3     3  
Leiomyoma † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Lymphoma † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Prostate cancer † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Renal cell carcinoma † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Retroperitoneal neoplasm metastatic † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Skin cancer † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     2  
Nervous system disorders      
Cerebral haemorrhage † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Convulsion † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Transient ischaemic attack † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Psychiatric disorders      
Abnormal behaviour † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Panic attack † 1    
# participants affected / at risk     2/382 (0.52%)     0/388 (0.00%)  
# events     2     0  
Suicidal ideation † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Suicide attempt † 1    
# participants affected / at risk     1/382 (0.26%)     4/388 (1.03%)  
# events     1     4  
Renal and urinary disorders      
Nephrolithiasis † 1    
# participants affected / at risk     1/382 (0.26%)     1/388 (0.26%)  
# events     1     1  
Renal colic † 1    
# participants affected / at risk     2/382 (0.52%)     0/388 (0.00%)  
# events     3     0  
Renal failure acute † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Reproductive system and breast disorders      
Amenorrhoea † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Epididymitis † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Respiratory, thoracic and mediastinal disorders      
Pleural effusion † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Skin and subcutaneous tissue disorders      
Hypoaesthesia facial † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Psoriasis † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     1  
Vascular disorders      
Aortic aneurysm † 1    
# participants affected / at risk     1/382 (0.26%)     0/388 (0.00%)  
# events     1     0  
Deep vein thrombosis † 1    
# participants affected / at risk     0/382 (0.00%)     1/388 (0.26%)  
# events     0     2  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 14.0




  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