Safety and Efficacy of an Investigational Drug in Human Immunodeficiency Virus (HIV)-Infected Patients Failing Current Antiretroviral Therapies (0518-005)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00105157
First received: March 8, 2005
Last updated: November 27, 2013
Last verified: November 2013
Results First Received: September 14, 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
Conditions: HIV Infections
Acquired Immunodeficiency Syndrome
Interventions: Drug: Comparator: MK0518
Drug: MK0518
Drug: Placebo

  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: 22-Apr-2005 to 09-Nov-2006

Multicenter (31) in the United States (15) and outside the United States (16)


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients failed prior antiretroviral therapy (HIV RNA >5000 copies/mL), and had documented resistance to at least one drug in each class of licensed oral antiretroviral therapy (Nucleoside Reverse Transcriptase inhibitors, Non-Nucleoside Reverse Transcriptase inhibitors and Protease Inhibitors). All patients must have met laboratory criteria.

Reporting Groups
  Description
MK0518 200 mg b.i.d. Optimized background antiretroviral therapy (OBT), if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 200 mg twice a day (b.i.d.). Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
MK0518 400 mg b.i.d. OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 400 mg b.i.d.
MK0518 600 mg b.i.d. OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 600 mg b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
Placebo OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 matching placebo b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.

Participant Flow for 3 periods

Period 1:   Double-Blind (DB)
    MK0518 200 mg b.i.d.     MK0518 400 mg b.i.d.     MK0518 600 mg b.i.d.     Placebo  
STARTED     44     45     45     45  
Treated     43     45     45     45  
COMPLETED     30     31     33     6  
NOT COMPLETED     14     14     12     39  
Never Treated                 1                 0                 0                 0  
Adverse Event                 2                 0                 1                 1  
Lack of Efficacy                 11                 14                 11                 38  

Period 2:   Open-Label Continuation of DB
    MK0518 200 mg b.i.d.     MK0518 400 mg b.i.d.     MK0518 600 mg b.i.d.     Placebo  
STARTED     30     31     33     6  
COMPLETED     23     21     24     5  
NOT COMPLETED     7     10     9     1  
Adverse Event                 3                 1                 0                 0  
Lack of Efficacy                 1                 4                 3                 1  
Lost to Follow-up                 1                 1                 1                 0  
Withdrawal by Subject                 0                 1                 3                 0  
Patient did not continue in extension                 1                 0                 0                 0  
Patient moved/site stopped trial                 1                 3                 2                 0  

Period 3:   Open-Label Post Virologic Failure(OLPVF)
    MK0518 200 mg b.i.d.     MK0518 400 mg b.i.d.     MK0518 600 mg b.i.d.     Placebo  
STARTED     11 [1]   13 [1]   11 [1]   37 [1]
COMPLETED     2     7     5     19  
NOT COMPLETED     9     6     6     18  
Adverse Event                 0                 0                 0                 1  
Lack of Efficacy                 7                 6                 5                 10  
Lost to Follow-up                 1                 0                 0                 1  
Withdrawal by Subject                 0                 0                 0                 5  
Patient moved/Site stopped trial                 1                 0                 1                 1  
[1] Number of Patients appropriate for and who consented to enter the OLPVF



  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
MK0518 200 mg b.i.d. Optimized background antiretroviral therapy (OBT), if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 200 mg twice a day (b.i.d.). Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
MK0518 400 mg b.i.d. OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 400 mg b.i.d.
MK0518 600 mg b.i.d. OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 600 mg b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
Placebo OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 matching placebo b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
Total Total of all reporting groups

Baseline Measures
    MK0518 200 mg b.i.d.     MK0518 400 mg b.i.d.     MK0518 600 mg b.i.d.     Placebo     Total  
Number of Participants  
[units: participants]
  43     45     45     45     178  
Age  
[units: years]
Mean ( Full Range )
  44.0  
  ( 18 to 57 )  
  45.1  
  ( 32 to 69 )  
  43.8  
  ( 25 to 63 )  
  43.3  
  ( 29 to 59 )  
  44.1  
  ( 18 to 69 )  
Gender  
[units: participants]
         
Female     7     5     4     5     21  
Male     36     40     41     40     157  
Race/Ethnicity, Customized  
[units: participants]
         
White     36     35     32     33     136  
Black     3     5     7     5     20  
Asian     0     0     2     1     3  
Hispanic     4     5     4     5     18  
Others     0     0     0     1     1  
Cluster of Differentiation 4 (CD4) Cell Count  
[units: Cells/mm3]
Mean ( Full Range )
  244.9  
  ( 30 to 1153 )  
  220.6  
  ( 68 to 673 )  
  220.4  
  ( 30 to 663 )  
  274.0  
  ( 37 to 880 )  
  239.9  
  ( 30 to 1153 )  
Plasma HIV RNA  
[units: log10┬ácopies/mL]
Mean ( Full Range )
  4.6  
  ( 3.5 to 5.9 )  
  4.8  
  ( 3.7 to 5.9 )  
  4.7  
  ( 3.8 to 5.8 )  
  4.7  
  ( 3.6 to 5.8 )  
  4.7  
  ( 3.5 to 5.9 )  
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA)  
[units: Copies/mL]
Mean ( Full Range )
  44642.6  
  ( 3000 to 750000 )  
  59107.9  
  ( 4770 to 750000 )  
  49064.8  
  ( 7030 to 589000 )  
  47432.6  
  ( 3630 to 611000 )  
  49841.6  
  ( 3000 to 750000 )  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Plasma HIV RNA (log10 Copies/mL) at Week 24   [ Time Frame: Baseline and Week 24 ]

2.  Secondary:   Number of Patients With Virologic Responses at Week 24   [ Time Frame: 24 weeks ]

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

4.  Secondary:   Number of Patients With Clinical Adverse Experiences (CAEs) at 48 Weeks   [ Time Frame: 48 weeks ]

5.  Secondary:   Number of Patients With Serious CAEs at 48 Weeks   [ Time Frame: 48 weeks ]
  Hide Outcome Measure 5

Measure Type Secondary
Measure Title Number of Patients With Serious CAEs at 48 Weeks
Measure Description Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose
Time Frame 48 weeks  
Safety Issue Yes  

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 patients who took study medication were included in the analysis.

Reporting Groups
  Description
MK0518 200 mg b.i.d. Optimized background antiretroviral therapy (OBT), if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 200 mg twice a day (b.i.d.). Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
MK0518 400 mg b.i.d. OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 400 mg b.i.d.
MK0518 600 mg b.i.d. OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 600 mg b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
Placebo OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 matching placebo b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.

Measured Values
    MK0518 200 mg b.i.d.     MK0518 400 mg b.i.d.     MK0518 600 mg b.i.d.     Placebo  
Number of Participants Analyzed  
[units: participants]
  43     45     45     45  
Number of Patients With Serious CAEs at 48 Weeks  
[units: Participants]
       
With Serious CAEs     3     7     4     3  
Without Serious CAEs     40     38     41     42  

No statistical analysis provided for Number of Patients With Serious CAEs at 48 Weeks



6.  Secondary:   Number of Patients With Drug-related CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

7.  Secondary:   Number of Patients With Serious Drug-related CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

8.  Secondary:   Number of Patients That Died by 48 Weeks   [ Time Frame: 48 weeks ]

9.  Secondary:   Number of Patients That Discontinued With CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

10.  Secondary:   Number of Patients That Discontinued With Drug-related CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

11.  Secondary:   Number of Patients That Discontinued With Serious CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

12.  Secondary:   Number of Patients That Discontinued With Serious Drug-related CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

13.  Secondary:   Number of Patients With Laboratory Adverse Experiences (LAEs) at 48 Weeks   [ Time Frame: 48 weeks ]

14.  Secondary:   Number of Patients With Drug-related LAEs at 48 Weeks   [ Time Frame: 48 weeks ]

15.  Secondary:   Number of Patients Discontinued With Laboratory Adverse Experiences (LAEs) at 48 Weeks   [ Time Frame: 48 weeks ]

16.  Secondary:   Number of Patients Discontinued With Drug-related LAEs at 48 Weeks   [ Time Frame: 48 weeks ]

17.  Secondary:   Number of Patients With Clinical Adverse Experiences (CAEs) at 96 Weeks   [ Time Frame: 96 weeks ]

18.  Secondary:   Number of Patients With Serious CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

19.  Secondary:   Number of Patients With Drug-related CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

20.  Secondary:   Number of Patients With Serious Drug-related CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

21.  Secondary:   Number of Patients That Died by 96 Weeks   [ Time Frame: 96 weeks ]

22.  Secondary:   Number of Patients That Discontinued With CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

23.  Secondary:   Number of Patients That Discontinued With Drug-related CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

24.  Secondary:   Number of Patients That Discontinued With Serious CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

25.  Secondary:   Number of Patients That Discontinued With Serious Drug-related CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

26.  Secondary:   Number of Patients With Laboratory Adverse Experiences (LAEs) at 96 Weeks   [ Time Frame: 96 weeks ]

27.  Secondary:   Number of Patients With Drug-related LAEs at 96 Weeks   [ Time Frame: 96 weeks ]

28.  Secondary:   Number of Patients Discontinued With Laboratory Adverse Experiences (LAEs) at 96 Weeks   [ Time Frame: 96 weeks ]

29.  Secondary:   Number of Patients Discontinued With Drug-related LAEs at 96 Weeks   [ Time Frame: 96 weeks ]

30.  Secondary:   Number of Patients With Clinical Adverse Experiences (CAEs) at 168 Weeks   [ Time Frame: 168 weeks ]

31.  Secondary:   Number of Patients With Serious CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

32.  Secondary:   Number of Patients With Drug-related CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

33.  Secondary:   Number of Patients With Serious Drug-related CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

34.  Secondary:   Number of Patients That Died by 168 Weeks   [ Time Frame: 168 weeks ]

35.  Secondary:   Number of Patients That Discontinued With CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

36.  Secondary:   Number of Patients That Discontinued With Drug-related CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

37.  Secondary:   Number of Patients That Discontinued With Serious CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

38.  Secondary:   Number of Patients That Discontinued With Serious Drug-related CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

39.  Secondary:   Number of Patients With Laboratory Adverse Experiences (LAEs) at 168 Weeks   [ Time Frame: 168 weeks ]

40.  Secondary:   Number of Patients With Serious LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

41.  Secondary:   Number of Patients Discontinued With Drug-related LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

42.  Secondary:   Number of Patients With Drug-related LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

43.  Secondary:   Number of Patients With Serious Drug-related LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

44.  Secondary:   Number of Patients Discontinued With LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

45.  Post-Hoc:   Number of Patients With Virologic Responses at Week 168 in Combined Substudies   [ Time Frame: 168 weeks ]

46.  Other Pre-specified:   Change From Baseline in Plasma HIV RNA (log10 Copies/mL) at Week 168 in Combined Substudies   [ Time Frame: Baseline and Week 168 ]

47.  Other Pre-specified:   Change From Baseline in CD4 Cell Count at Week 168 in Combined Substudies   [ Time Frame: Baseline and Week 168 ]


  Serious Adverse Events


  Other Adverse Events


  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.


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
Due to a 3:1 randomization of MK-0518 to placebo and more discontinuations for placebo in the doubleblind phase, exposure for MK-0518 and placebo differs significantly with follow-up times of 336.3 and 39.7 patient-years, respectively.  


Results Point of Contact:  
Name/Title: Executive Vice President, Clinical and Quantitative Sciences
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372


Publications:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00105157     History of Changes
Other Study ID Numbers: 0518-005, MK0518-005, 2005_007
Study First Received: March 8, 2005
Results First Received: September 14, 2009
Last Updated: November 27, 2013
Health Authority: United States: Food and Drug Administration