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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
  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

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 ]

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
  Hide Other Adverse Events

Time Frame 240 weeks
Additional Description Adverse events are reported for the entire 240-week study.

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

Reporting Groups
  Description
MK-0518 400 mg b.i.d. MK-0518 400 mg taken by mouth (PO) twice a day (b.i.d.) without regard to food, and placebo to efavirenz, taken PO (q.h.s.) on an empty stomach preferably at bedtime (q.h.s.). All participants will take one tablet of TRUVADA® (200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) daily with food 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 taken by mouth on an empty stomach preferably at bedtime (q.h.s.), and placebo to MK-0518 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.

Other Adverse Events
    MK-0518 400 mg b.i.d.     Efavirenz 600 mg q.h.s.  
Total, other (not including serious) adverse events      
# participants affected / at risk     257/281     263/282  
Gastrointestinal disorders      
Abdominal pain † 1    
# participants affected / at risk     24/281 (8.54%)     19/282 (6.74%)  
# events     30     23  
Abdominal pain upper † 1    
# participants affected / at risk     8/281 (2.85%)     19/282 (6.74%)  
# events     16     20  
Diarrhoea † 1    
# participants affected / at risk     72/281 (25.62%)     76/282 (26.95%)  
# events     104     105  
Dyspepsia † 1    
# participants affected / at risk     25/281 (8.90%)     14/282 (4.96%)  
# events     27     18  
Flatulence † 1    
# participants affected / at risk     14/281 (4.98%)     19/282 (6.74%)  
# events     17     19  
Nausea † 1    
# participants affected / at risk     47/281 (16.73%)     41/282 (14.54%)  
# events     68     52  
Vomiting † 1    
# participants affected / at risk     23/281 (8.19%)     30/282 (10.64%)  
# events     29     38  
General disorders      
Asthenia † 1    
# participants affected / at risk     17/281 (6.05%)     16/282 (5.67%)  
# events     24     16  
Fatigue † 1    
# participants affected / at risk     26/281 (9.25%)     38/282 (13.48%)  
# events     29     46  
Pyrexia † 1    
# participants affected / at risk     44/281 (15.66%)     39/282 (13.83%)  
# events     62     50  
Infections and infestations      
Bronchitis † 1    
# participants affected / at risk     29/281 (10.32%)     30/282 (10.64%)  
# events     48     48  
Gastroenteritis † 1    
# participants affected / at risk     17/281 (6.05%)     19/282 (6.74%)  
# events     19     20  
Genital herpes † 1    
# participants affected / at risk     12/281 (4.27%)     15/282 (5.32%)  
# events     17     19  
Herpes zoster † 1    
# participants affected / at risk     14/281 (4.98%)     16/282 (5.67%)  
# events     17     19  
Influenza † 1    
# participants affected / at risk     33/281 (11.74%)     38/282 (13.48%)  
# events     58     68  
Nasopharyngitis † 1    
# participants affected / at risk     75/281 (26.69%)     63/282 (22.34%)  
# events     121     123  
Pharyngitis † 1    
# participants affected / at risk     27/281 (9.61%)     26/282 (9.22%)  
# events     33     33  
Sinusitis † 1    
# participants affected / at risk     23/281 (8.19%)     23/282 (8.16%)  
# events     31     31  
Upper respiratory tract infection † 1    
# participants affected / at risk     60/281 (21.35%)     57/282 (20.21%)  
# events     95     85  
Investigations      
Alanine aminotransferase increased † 1    
# participants affected / at risk     19/281 (6.76%)     28/282 (9.93%)  
# events     33     49  
Aspartate aminotransferase increased † 1    
# participants affected / at risk     21/281 (7.47%)     25/282 (8.87%)  
# events     37     44  
Metabolism and nutrition disorders      
Decreased appetite † 1    
# participants affected / at risk     12/281 (4.27%)     19/282 (6.74%)  
# events     18     20  
Musculoskeletal and connective tissue disorders      
Arthralgia † 1    
# participants affected / at risk     24/281 (8.54%)     33/282 (11.70%)  
# events     29     34  
Back pain † 1    
# participants affected / at risk     34/281 (12.10%)     28/282 (9.93%)  
# events     43     34  
Myalgia † 1    
# participants affected / at risk     11/281 (3.91%)     15/282 (5.32%)  
# events     12     19  
Pain in extremity † 1    
# participants affected / at risk     18/281 (6.41%)     15/282 (5.32%)  
# events     23     17  
Nervous system disorders      
Dizziness † 1    
# participants affected / at risk     46/281 (16.37%)     108/282 (38.30%)  
# events     49     140  
Headache † 1    
# participants affected / at risk     73/281 (25.98%)     80/282 (28.37%)  
# events     127     109  
Somnolence † 1    
# participants affected / at risk     3/281 (1.07%)     22/282 (7.80%)  
# events     5     27  
Psychiatric disorders      
Abnormal dreams † 1    
# participants affected / at risk     23/281 (8.19%)     37/282 (13.12%)  
# events     29     43  
Anxiety † 1    
# participants affected / at risk     25/281 (8.90%)     31/282 (10.99%)  
# events     25     31  
Depression † 1    
# participants affected / at risk     27/281 (9.61%)     33/282 (11.70%)  
# events     32     38  
Insomnia † 1    
# participants affected / at risk     44/281 (15.66%)     42/282 (14.89%)  
# events     56     49  
Nightmare † 1    
# participants affected / at risk     10/281 (3.56%)     15/282 (5.32%)  
# events     12     19  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     47/281 (16.73%)     34/282 (12.06%)  
# events     64     47  
Oropharyngeal pain † 1    
# participants affected / at risk     22/281 (7.83%)     15/282 (5.32%)  
# events     22     15  
Rhinitis allergic † 1    
# participants affected / at risk     18/281 (6.41%)     6/282 (2.13%)  
# events     20     8  
Skin and subcutaneous tissue disorders      
Pruritus † 1    
# participants affected / at risk     12/281 (4.27%)     15/282 (5.32%)  
# events     12     15  
Rash † 1    
# participants affected / at risk     22/281 (7.83%)     39/282 (13.83%)  
# events     26     46  
Vascular disorders      
Hypertension † 1    
# participants affected / at risk     18/281 (6.41%)     18/282 (6.38%)  
# events     20     20  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 14.1



  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
No text entered.


  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: Executive Vice President, Late-Stage Development Group Leader
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, 2006_519
Study First Received: August 29, 2006
Results First Received: September 18, 2009
Last Updated: September 26, 2014
Health Authority: United States: Food and Drug Administration