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A Study to Evaluate the Safety and Antiretroviral Activity of MK-0518 Versus Efavirenz in Treatment Naive HIV-Infected Patients, Each in Combination With TRUVADA (0518-021 EXT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00369941
First received: August 29, 2006
Last updated: September 26, 2014
Last verified: September 2014
Results First Received: September 18, 2009  
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 Infections
Interventions: Drug: MK-0518
Drug: Comparator: efavirenz
Drug: Comparator: Truvada
Drug: Comparator: Placebo to MK-0518
Drug: Comparator: Placebo to efavirenz

  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

Primary therapy period: 14-Sep-2006 to 06-May-2009

Multicenter (67) in the United States (18) and Ex-US (49)


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
MK-0518 400 mg b.i.d. MK-0518 400 mg, which can be taken by mouth (PO) twice a day (b.i.d.) without regard to food, and placebo to efavirenz, which will be taken PO at bedtime (q.h.s.) on an empty stomach preferably at bedtime. All participants will take one tablet of TRUVADA® (200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) with food, daily with the morning dose of MK-0518. Dosing interval adjustment of TRUVADA® is recommended in all participants with creatinine clearance 30-49 mL/min.
Efavirenz 600 mg q.h.s. Efavirenz 600 mg, which will be taken by mouth (PO) at bedtime (q.h.s.) on an empty stomach preferably at bedtime, and placebo to MK-0518, which will be taken PO twice a day (b.i.d.) without regard to food. All participants will take one tablet of TRUVADA® with food, daily with the morning dose of placebo. Dosing interval adjustment of TRUVADA® is recommended in all participants with creatinine clearance 30-49 mL/min.

Participant Flow:   Overall Study
    MK-0518 400 mg b.i.d.     Efavirenz 600 mg q.h.s.  
STARTED     282     284  
Treated     281     282  
COMPLETED     210     184  
NOT COMPLETED     72     100  
Never Treated                 1                 2  
Adverse Event                 14                 28  
Lack of Efficacy                 6                 10  
Lost to Follow-up                 12                 22  
Protocol Violation                 5                 3  
Withdrawal by Subject                 5                 18  
Pregnancy                 4                 2  
Completed, Did Not Enter Extension                 5                 6  
Moved                 11                 5  
Treatment with Prohibited Medication                 3                 1  
Employment Interfered with Study Visits                 1                 0  
Study Site Terminated                 2                 0  
Miscellaneous                 3                 3  



  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
MK-0518 400 mg b.i.d. MK-0518 400 mg, which can be taken by mouth (PO) twice a day (b.i.d.) without regard to food, and placebo to efavirenz, which will be taken PO at bedtime (q.h.s.) on an empty stomach preferably at bedtime. All participants will take one tablet of TRUVADA® (200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) with food, daily with the morning dose of MK-0518. Dosing interval adjustment of TRUVADA® is recommended in all participants with creatinine clearance 30-49 mL/min.
Efavirenz 600 mg q.h.s. Efavirenz 600 mg, which will be taken by mouth (PO) at bedtime (q.h.s.) on an empty stomach preferably at bedtime, and placebo to MK-0518, which will be taken PO twice a day (b.i.d.) without regard to food. All participants will take one tablet of TRUVADA® with food, daily with the morning dose of placebo. Dosing interval adjustment of TRUVADA® is recommended in all participants with creatinine clearance 30-49 mL/min.
Total Total of all reporting groups

Baseline Measures
    MK-0518 400 mg b.i.d.     Efavirenz 600 mg q.h.s.     Total  
Number of Participants  
[units: participants]
  281     282     563  
Age  
[units: years]
Mean ( Full Range )
  38  
  ( 19 to 67 )  
  37  
  ( 19 to 71 )  
  37  
  ( 19 to 71 )  
Gender  
[units: participants]
     
Female     54     51     105  
Male     227     231     458  
Race/Ethnicity, Customized  
[units: participants]
     
White     116     123     239  
Black     33     23     56  
Asian     36     32     68  
Hispanic     60     67     127  
Others     36     37     73  
Cluster of Differentiation 4 (CD4) Cell Count  
[units: Cells/mm^3]
Mean ( Full Range )
  219  
  ( 1 to 620 )  
  217  
  ( 4 to 807 )  
  218  
  ( 1 to 807 )  
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA)  
[units: Copies/mL]
Geometric Mean ( Full Range )
  103205  
  ( 400 to 750000 )  
  106215  
  ( 4410 to 750000 )  
  104702  
  ( 400 to 750000 )  



  Outcome Measures
  Show All Outcome Measures

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

2.  Primary:   Number of Participants With Clinical Adverse Experiences (CAEs) at Week 48   [ Time Frame: 48 Weeks ]

3.  Primary:   Number of Participants With Serious CAEs at Week 48   [ Time Frame: 48 Weeks ]

4.  Primary:   Number of Participants With Drug-related CAEs at Week 48   [ Time Frame: 48 Weeks ]

5.  Primary:   Number of Participants With Serious Drug-related CAEs at Week 48   [ Time Frame: 48 Weeks ]

6.  Primary:   Number of Participants That Died by Week 48   [ Time Frame: 48 Weeks ]

7.  Primary:   Number of Participants That Discontinued With CAEs at Week 48   [ Time Frame: 48 Weeks ]

8.  Primary:   Number of Participants That Discontinued With Serious CAEs at Week 48   [ Time Frame: 48 Weeks ]

9.  Primary:   Number of Participants That Discontinued With Drug-related CAEs at Week 48   [ Time Frame: 48 Weeks ]

10.  Primary:   Number of Participants That Discontinued With Serious Drug-related CAEs at Week 48   [ Time Frame: 48 Weeks ]

11.  Primary:   Number of Participants With Laboratory Adverse Experiences (LAEs) at Week 48   [ Time Frame: 48 Weeks ]

12.  Primary:   Number of Participants With Serious LAEs at Week 48   [ Time Frame: 48 Weeks ]

13.  Primary:   Number of Participants With Drug-related LAEs at Week 48   [ Time Frame: 48 Weeks ]

14.  Primary:   Number of Participants With Serious Drug-related LAEs at Week 48   [ Time Frame: 48 Weeks ]

15.  Primary:   Number of Participants Discontinued With LAEs at Week 48   [ Time Frame: 48 Weeks ]

16.  Primary:   Number of Participants Discontinued With Drug-related LAEs at Week 48   [ Time Frame: 48 Weeks ]

17.  Secondary:   Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 48   [ Time Frame: 48 Weeks ]

18.  Secondary:   Change From Baseline in Cluster of Differentiation Antigen 4 (CD4) Cell Count at Week 48   [ Time Frame: Baseline and Week 48 ]

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

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

21.  Secondary:   Change From Baseline in CD4 Cell Count at Week 96   [ Time Frame: Baseline and Week 96 ]

22.  Secondary:   Number of Participants Who Achieved HIV RNA <50 Copies/mL at Week 156   [ Time Frame: 156 Weeks ]
  Hide Outcome Measure 22

Measure Type Secondary
Measure Title Number of Participants Who Achieved HIV RNA <50 Copies/mL at Week 156
Measure Description Antiretroviral activity was evaluated for participants who achieved HIV RNA level <50 copies/mL at Week 156.
Time Frame 156 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.
All participants who took study medication and had HIV RNA tests performed were included in the analysis.

Reporting Groups
  Description
MK-0518 400 mg b.i.d. MK-0518 400 mg, which can be taken by mouth (PO) twice a day (b.i.d.) without regard to food, and placebo to efavirenz, which will be taken PO at bedtime (q.h.s.) on an empty stomach preferably at bedtime. All participants will take one tablet of TRUVADA® (200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) with food, daily with the morning dose of MK-0518. Dosing interval adjustment of TRUVADA® is recommended in all participants with creatinine clearance 30-49 mL/min.
Efavirenz 600 mg q.h.s. Efavirenz 600 mg, which will be taken by mouth (PO) at bedtime (q.h.s.) on an empty stomach preferably at bedtime, and placebo to MK-0518, which will be taken PO twice a day (b.i.d.) without regard to food. All participants will take one tablet of TRUVADA® with food, daily with the morning dose of placebo. Dosing interval adjustment of TRUVADA® is recommended in all participants with creatinine clearance 30-49 mL/min.

Measured Values
    MK-0518 400 mg b.i.d.     Efavirenz 600 mg q.h.s.  
Number of Participants Analyzed  
[units: participants]
  281     282  
Number of Participants Who Achieved HIV RNA <50 Copies/mL at Week 156  
[units: Participants]
  212     192  

No statistical analysis provided for Number of Participants Who Achieved HIV RNA <50 Copies/mL at Week 156



23.  Secondary:   Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 156   [ Time Frame: 156 Weeks ]

24.  Secondary:   Change From Baseline in CD4 Cell Count at Week 156   [ Time Frame: Baseline and Week 156 ]

25.  Secondary:   Number of Participants Who Achieved HIV RNA <50 Copies/mL at Week 240   [ Time Frame: 240 Weeks ]

26.  Secondary:   Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 240   [ Time Frame: 240 Weeks ]

27.  Secondary:   Change From Baseline in CD4 Cell Count at Week 240   [ Time Frame: Baseline and Week 240 ]

28.  Secondary:   Number of Participants With Nervous System Symptoms Assessed by Review of Accumulated Safety Data up to Week 8   [ Time Frame: 8 Weeks ]

29.  Secondary:   Number of Participants With CAEs at Week 96   [ Time Frame: 96 Weeks ]

30.  Secondary:   Number of Participants With CAEs at Week 156   [ Time Frame: 156 Weeks ]

31.  Secondary:   Number of Participants With CAEs at Week 240   [ Time Frame: 240 Weeks ]

32.  Secondary:   Number of Participants With Serious CAEs at Week 96   [ Time Frame: 96 Weeks ]

33.  Secondary:   Number of Participants With Serious CAEs at Week 156   [ Time Frame: 156 Weeks ]

34.  Secondary:   Number of Participants With Serious CAEs at Week 240   [ Time Frame: 240 Weeks ]

35.  Secondary:   Number of Participants With Drug-related CAEs at Week 96   [ Time Frame: 96 Weeks ]

36.  Secondary:   Number of Participants With Drug-related CAEs at Week 156   [ Time Frame: 156 Weeks ]

37.  Secondary:   Number of Participants With Drug-related CAEs at Week 240   [ Time Frame: 240 Weeks ]

38.  Secondary:   Number of Participants With Serious Drug-related CAEs at Week 96   [ Time Frame: 96 Weeks ]

39.  Secondary:   Number of Participants With Serious Drug-related CAEs at Week 156   [ Time Frame: 156 Weeks ]

40.  Secondary:   Number of Participants With Serious Drug-related CAEs at Week 240   [ Time Frame: 240 Weeks ]

41.  Secondary:   Number of Participants That Died by Week 96   [ Time Frame: 96 Weeks ]

42.  Secondary:   Number of Participants That Died by Week 156   [ Time Frame: 156 Weeks ]

43.  Secondary:   Number of Participants That Died by Week 240   [ Time Frame: 240 Weeks ]

44.  Secondary:   Number of Participants That Discontinued With CAEs at Week 96   [ Time Frame: 96 Weeks ]

45.  Secondary:   Number of Participants That Discontinued With CAEs at Week 156   [ Time Frame: 156 Weeks ]

46.  Secondary:   Number of Participants That Discontinued With CAEs at Week 240   [ Time Frame: 240 Weeks ]

47.  Secondary:   Number of Participants That Discontinued With Drug-related CAEs at Week 96   [ Time Frame: 96 Weeks ]

48.  Secondary:   Number of Participants That Discontinued With Drug-related CAEs at Week 156   [ Time Frame: 156 Weeks ]

49.  Secondary:   Number of Participants That Discontinued With Drug-related CAEs at Week 240   [ Time Frame: 240 Weeks ]

50.  Secondary:   Number of Participants That Discontinued With Serious CAEs at Week 96   [ Time Frame: 96 Weeks ]

51.  Secondary:   Number of Participants That Discontinued With Serious CAEs at Week 156   [ Time Frame: 156 Weeks ]

52.  Secondary:   Number of Participants That Discontinued With Serious CAEs at Week 240   [ Time Frame: 240 Weeks ]

53.  Secondary:   Number of Participants That Discontinued With Serious Drug-related CAEs at Week 96   [ Time Frame: 96 Weeks ]

54.  Secondary:   Number of Participants That Discontinued With Serious Drug-related CAEs at Week 156   [ Time Frame: 156 Weeks ]

55.  Secondary:   Number of Participants That Discontinued With Serious Drug-related CAEs at Week 240   [ Time Frame: 240 Weeks ]

56.  Secondary:   Number of Participants With LAEs at Week 96   [ Time Frame: 96 Weeks ]

57.  Secondary:   Number of Participants With LAEs at Week 156   [ Time Frame: 156 Weeks ]

58.  Secondary:   Number of Participants With LAEs at Week 240   [ Time Frame: 240 Weeks ]

59.  Secondary:   Number of Participants With Drug-related LAEs at Week 96   [ Time Frame: 96 Weeks ]

60.  Secondary:   Number of Participants With Drug-related LAEs at Week 156   [ Time Frame: 156 Weeks ]

61.  Secondary:   Number of Participants With Drug-related LAEs at Week 240   [ Time Frame: 240 Weeks ]

62.  Secondary:   Number of Participants With Serious LAEs at Week 96   [ Time Frame: 96 Weeks ]

63.  Secondary:   Number of Participants With Serious LAEs at Week 156   [ Time Frame: 156 Weeks ]

64.  Secondary:   Number of Participants With Serious LAEs at Week 240   [ Time Frame: 240 Weeks ]

65.  Secondary:   Number of Participants With Serious Drug-related LAEs at Week 96   [ Time Frame: 96 Weeks ]

66.  Secondary:   Number of Participants With Serious Drug-related LAEs at Week 156   [ Time Frame: 156 Weeks ]

67.  Secondary:   Number of Participants With Serious Drug-related LAEs at Week 240   [ Time Frame: 240 Weeks ]

68.  Secondary:   Number of Participants Discontinued With LAEs at Week 96   [ Time Frame: 96 Weeks ]

69.  Secondary:   Number of Participants Discontinued With LAEs at Week 156   [ Time Frame: 156 Weeks ]

70.  Secondary:   Number of Participants Discontinued With LAEs at Week 240   [ Time Frame: 240 Weeks ]

71.  Secondary:   Number of Participants Discontinued With Drug-related LAEs at Week 96   [ Time Frame: 96 Weeks ]

72.  Secondary:   Number of Participants Discontinued With Drug-related LAEs at Week 156   [ Time Frame: 156 Weeks ]

73.  Secondary:   Number of Participants Discontinued With Drug-related LAEs at Week 240   [ Time Frame: 240 Weeks ]


  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
No text entered.


  More Information