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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 1, 2015
Last verified: September 2015
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 
Overall Participants Analyzed 
[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 ]
  Hide Outcome Measure 19

Measure Type Secondary
Measure Title Number of Participants Who Achieved HIV RNA <50 Copies/mL at Week 96
Measure Description Antiretroviral activity was evaluated for participants who achieved HIV RNA level <50 copies/mL at Week 96.
Time Frame 96 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. 
Participants Analyzed 
[Units: Participants]
 281   282 
Number of Participants Who Achieved HIV RNA <50 Copies/mL at Week 96 
[Units: Participants]
 228   222 

No statistical analysis provided for Number of Participants Who Achieved HIV RNA <50 Copies/mL at Week 96



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 ]

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