MK0518 in the Treatment of HIV-Infected Patients Switched From a Protease Inhibitor Regimen (0518-033)(TERMINATED)

This study has been terminated.
(Primary efficacy analysis at Week 24 did not demonstrate non-inferiority of raltegravir versus lopinavir (+) ritonavir)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00443729
First received: March 2, 2007
Last updated: October 15, 2013
Last verified: October 2013
Results First Received: October 12, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: HIV Infection
Interventions: Drug: Comparator: raltegravir
Drug: Comparator: placebo
Drug: Comparator: lopinavir (+) ritonavir

  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

Phase III; First Patient In: 11-Jun-2007; Last Patient Last Visit for Week 24 (primary endpoint): 17-Oct-

2008

34 Sites (US, Peru, Brazil, Colombia, Mexico, South Africa, Thailand, India, and Australia).


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
HIV-seropositive patients who were ≥18 years old, had documented HIV RNA <50 copies/mL for at least 3 months, had been on a KALETRA™-based regimen for at least 3 months without a change in background antiretroviral therapy, and had no documentation of HIV RNA >50 copies/mL for at least 3 months.

Reporting Groups
  Description
MK0518 400 mg b.i.d. MK0518 400 mg, which can be taken by mouth (PO) twice a day (b.i.d.), approximately 12 hours (10 to 14 hours) apart without regard to food, and placebo to KALETRA™ , which can be taken by mouth (PO) twice a day (b.i.d.), approximately 12 hours (10 to 14 hours) apart without regard to food
KALETRA™ 400/100 mg b.i.d. KALETRA™ 400/100 mg, which can be taken by mouth (PO) twice a day (b.i.d.), approximately 12 hours (10 to 14 hours) apart without regard to food, and placebo to MK0518 , which can be taken by mouth (PO) twice a day (b.i.d.), approximately 12 hours (10 to 14 hours) apart without regard to food

Participant Flow:   Overall Study
    MK0518 400 mg b.i.d.     KALETRA™ 400/100 mg b.i.d.  
STARTED     176     179  
Treated     176     178  
COMPLETED     166     172  
NOT COMPLETED     10     7  
Never Treated                 0                 1  
Lack of Efficacy                 4                 2  
Lost to Follow-up                 0                 1  
Physician Decision                 2                 1  
Protocol Violation                 1                 1  
Withdrawal by Subject                 3                 1  



  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 400 mg b.i.d. MK0518 400 mg, which can be taken by mouth (PO) twice a day (b.i.d.), approximately 12 hours (10 to 14 hours) apart without regard to food, and placebo to KALETRA™ , which can be taken by mouth (PO) twice a day (b.i.d.), approximately 12 hours (10 to 14 hours) apart without regard to food
KALETRA™ 400/100 mg b.i.d. KALETRA™ 400/100 mg, which can be taken by mouth (PO) twice a day (b.i.d.), approximately 12 hours (10 to 14 hours) apart without regard to food, and placebo to MK0518 , which can be taken by mouth (PO) twice a day (b.i.d.), approximately 12 hours (10 to 14 hours) apart without regard to food
Total Total of all reporting groups

Baseline Measures
    MK0518 400 mg b.i.d.     KALETRA™ 400/100 mg b.i.d.     Total  
Number of Participants  
[units: participants]
  176     178     354  
Age  
[units: Years]
Mean ( Full Range )
  42.0  
  ( 21 to 71 )  
  41.9  
  ( 23 to 74 )  
  42.0  
  ( 21 to 74 )  
Gender  
[units: participants]
     
Female     39     40     79  
Male     137     138     275  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     68     73     141  
Not Hispanic or Latino     108     105     213  
Unknown or Not Reported     0     0     0  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     1     1  
Asian     26     28     54  
Native Hawaiian or Other Pacific Islander     0     1     1  
Black or African American     33     25     58  
White     85     81     166  
More than one race     32     42     74  
Unknown or Not Reported     0     0     0  
Cluster of Differentiation 4 (CD4) Cell Count  
[units: cells/mm3]
Mean ( Full Range )
  470.8  
  ( 16 to 1916 )  
  482.4  
  ( 100 to 1744 )  
  476.6  
  ( 16 to 1916 )  
Fasting (non-random) serum High-Density Lipoprotein-Cholesterol (HDL-C)  
[units: mg/dL]
Mean ± Standard Deviation
  46.5  ± 12.8     47.9  ± 12.7     47.2  ± 12.7  
Fasting (non-random) serum Low-Density Lipoprotein-Cholesterol (LDL-C)  
[units: mg/dL]
Mean ± Standard Deviation
  103.5  ± 41.0     104.3  ± 30.6     103.9  ± 36.2  
Fasting (non-random) serum cholesterol  
[units: mg/dL]
Mean ± Standard Deviation
  214.7  ± 69.7     210.8  ± 46.4     212.7  ± 59.2  
Fasting (non-random) serum triglyceride [1]
[units: mg/dL]
Mean ± Standard Deviation
  204.5  ± 156.3     217.5  ± 156.3     212.5  ± 156.3  
Non-HDL-C  
[units: mg/dL]
Mean ± Standard Deviation
  168.2  ± 71.8     163.4  ± 45.7     165.8  ± 60.3  
[1] Standard Deviation (Robust): calculated as interquartile range (IQR)/1.075, where IQR=3rd quartile-1st quartile.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Patients With Plasma Human Immunodeficiency Virus (HIV) RiboNucleic Acid (RNA) <50 Copies/mL at Week 24   [ Time Frame: 24 Weeks ]

2.  Primary:   Number of Patients With Clinical Adverse Experiences (CAEs) Through 24 Weeks   [ Time Frame: 24 Week last patient last visit ]

3.  Primary:   Mean Percent Change From Baseline in Fasting Serum Cholesterol at Week 12   [ Time Frame: Baseline and Week 12 ]

4.  Primary:   Mean Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Week 12   [ Time Frame: Baseline and Week 12 ]

5.  Primary:   Mean Percent Change From Baseline in Fasting Serum Low-density Lipoprotein Cholesterol (LDL-C) at Week 12   [ Time Frame: Baseline and Week 12 ]

6.  Primary:   Mean Percent Change From Baseline in Fasting Serum High-density Lipoprotein Cholesterol (HDL-C) at Week 12   [ Time Frame: Baseline and Week 12 ]
  Hide Outcome Measure 6

Measure Type Primary
Measure Title Mean Percent Change From Baseline in Fasting Serum High-density Lipoprotein Cholesterol (HDL-C) at Week 12
Measure Description No text entered.
Time Frame Baseline and Week 12  
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.
Patients who had both baseline and at least one post-baseline measurement were included in the analysis

Reporting Groups
  Description
MK0518 400 mg b.i.d. MK0518 400 mg, which can be taken by mouth (PO) twice a day (b.i.d.), approximately 12 hours (10 to 14 hours) apart without regard to food, and placebo to KALETRA™ , which can be taken by mouth (PO) twice a day (b.i.d.), approximately 12 hours (10 to 14 hours) apart without regard to food
KALETRA™ 400/100 mg b.i.d. KALETRA™ 400/100 mg, which can be taken by mouth (PO) twice a day (b.i.d.), approximately 12 hours (10 to 14 hours) apart without regard to food, and placebo to MK0518 , which can be taken by mouth (PO) twice a day (b.i.d.), approximately 12 hours (10 to 14 hours) apart without regard to food

Measured Values
    MK0518 400 mg b.i.d.     KALETRA™ 400/100 mg b.i.d.  
Number of Participants Analyzed  
[units: participants]
  166     162  
Mean Percent Change From Baseline in Fasting Serum High-density Lipoprotein Cholesterol (HDL-C) at Week 12  
[units: Percent┬áChange]
Mean ± Standard Deviation
  -0.64  ± 20.14     -2.50  ± 16.50  

No statistical analysis provided for Mean Percent Change From Baseline in Fasting Serum High-density Lipoprotein Cholesterol (HDL-C) at Week 12



7.  Primary:   Median Percent Change From Baseline in Serum Triglyceride at Week 12   [ Time Frame: Baseline and Week 12 ]

8.  Secondary:   Mean Percent Change From Baseline in Fasting Serum Cholesterol at Week 24   [ Time Frame: Baseline and Week 24 ]

9.  Secondary:   Mean Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24   [ Time Frame: Baseline and Week 24 ]

10.  Secondary:   Mean Percent Change From Baseline in Fasting Serum Low-density Lipoprotein Cholesterol (LDL-C) at Week 24   [ Time Frame: Baseline and Week 24 ]

11.  Secondary:   Mean Percent Change From Baseline in Fasting Serum High-density Lipoprotein Cholesterol (HDL-C) at Week 24   [ Time Frame: Baseline and Week 24 ]

12.  Secondary:   Median Percent Change From Baseline in Serum Triglyceride at Week 24   [ Time Frame: Baseline and Week 24 ]

13.  Other Pre-specified:   Number of Patients With Serious CAEs Through 24 Weeks   [ Time Frame: 24 Week last patient last visit ]

14.  Other Pre-specified:   Number of Patients With Drug-related CAEs Through 24 Weeks   [ Time Frame: 24 Week last patient last visit ]

15.  Other Pre-specified:   Number of Patients With Serious Drug-related CAEs Through 24 Weeks   [ Time Frame: 24 Week last patient last visit ]

16.  Other Pre-specified:   Number of Patients That Died by 24 Week Last Patient Last Visit   [ Time Frame: 24 Week last patient last visit ]

17.  Other Pre-specified:   Number of Patients That Discontinued Due to CAEs Through 24 Weeks   [ Time Frame: 24 Week last patient last visit ]

18.  Other Pre-specified:   Number of Patients With Laboratory Adverse Experiences (LAEs) Through 24 Weeks   [ Time Frame: 24 Week last patient last visit ]

19.  Other Pre-specified:   Number of Patients With Drug-related LAEs Through 24 Weeks   [ Time Frame: 24 Week last patient last visit ]

20.  Other Pre-specified:   Number of Patients With Serious LAEs Through 24 Weeks   [ Time Frame: 24 Week last patient last visit ]

21.  Other Pre-specified:   Number of Patients That Discontinued Due to LAEs Through 24 Weeks   [ Time Frame: 24 Week last patient last visit ]


  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
Study was terminated after the primary efficacy analysis at Week 24 did not demonstrate non-inferiority of MK0518 versus KALETRA™.  


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


No publications provided by Merck Sharp & Dohme Corp.

Publications automatically indexed to this study:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00443729     History of Changes
Other Study ID Numbers: 0518-033, 2007_508
Study First Received: March 2, 2007
Results First Received: October 12, 2009
Last Updated: October 15, 2013
Health Authority: United States: Food and Drug Administration