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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)

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ClinicalTrials.gov Identifier: NCT00369941
Recruitment Status : Completed
First Posted : August 30, 2006
Results First Posted : May 11, 2010
Last Update Posted : March 21, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, 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

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

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) 
Sex: Female, Male 
[Units: Participants]
Count of Participants 		     
Female      54  19.2%      51  18.1%      105  18.7% 
Male      227  80.8%      231  81.9%      458  81.3% 
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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Measure Type Secondary
Measure Title Number of Participants That Died by Week 240
Measure Description All participant deaths in the span of 240 weeks on study were recorded.
Time Frame 240 Weeks  

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 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 That Died by Week 240 
[Units: Participants]
 		   
Died   5   5 
Did Not Die   276   277 

No statistical analysis provided for Number of Participants That Died by Week 240



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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


  Serious Adverse Events


  Other Adverse Events


  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
No text entered.


  More Information

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 of Results:


Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00369941     History of Changes
Other Study ID Numbers: 0518-021
MK-0518-021 ( Other Identifier: Merck )
2006_519 ( Other Identifier: Merck Registration ID )
First Submitted: August 29, 2006
First Posted: August 30, 2006
Results First Submitted: September 18, 2009
Results First Posted: May 11, 2010
Last Update Posted: March 21, 2017