Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

MK0518 in the Treatment of HIV-Infected Patients Switched From a Protease Inhibitor Regimen (0518-032)(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:
NCT00443703
First received: March 2, 2007
Last updated: October 27, 2014
Last verified: October 2014
Results First Received: October 16, 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: MK0518 (raltegravir)
Drug: Comparator: KALETRA™ (lopinavir (+) ritonavir )
Drug: Comparator: placebo

  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

Phase III; First Patient In: 20-Jun-2007; Last Patient Last Visit for Week 24 (primary endpoint): 31-Oct-2008

47 Sites (US, Canada, Denmark, Germany, Italy, Portugal, Spain, United Kingdom, 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     177     175  
Treated     174     174  
COMPLETED     149     157  
NOT COMPLETED     28     18  
Never Treated                 3                 1  
Adverse Event                 7                 3  
Lack of Efficacy                 3                 1  
Lost to Follow-up                 0                 4  
Physician Decision                 4                 2  
Protocol Violation                 1                 1  
Withdrawal by Subject                 9                 6  
Progressive Disease                 1                 0  



  Baseline Characteristics
  Hide 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
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]
  174     174     348  
Age  
[units: years]
Mean ( Full Range )
  44.4  
  ( 23 to 70 )  
  43.6  
  ( 24 to 71 )  
  44.0  
  ( 23 to 71 )  
Gender  
[units: participants]
     
Female     28     45     73  
Male     146     129     275  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     25     23     48  
Not Hispanic or Latino     149     151     300  
Unknown or Not Reported     0     0     0  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     2     3     5  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     24     28     52  
White     146     141     287  
More than one race     2     2     4  
Unknown or Not Reported     0     0     0  
Cluster of Differentiation 4 (CD4) Cell Count  
[units: cells/mm3]
Mean ( Full Range )
  477.6  
  ( 65 to 1446 )  
  508.2  
  ( 87 to 1510 )  
  492.9  
  ( 65 to 1510 )  
Fasting (non-random) serum High Density Lipoprotein-Cholesterol (HDL-C)  
[units: mg/dL]
Mean ± Standard Deviation
  48.8  ± 16.4     47.1  ± 14.0     47.9  ± 15.2  
Fasting (non-random) serum Low Density Lipoprotein-Cholesterol (LDL-C)  
[units: mg/dL]
Mean ± Standard Deviation
  115.3  ± 40.3     104.8  ± 35.9     110.0  ± 38.5  
Fasting (non-random) serum cholesterol  
[units: mg/dL]
Mean ± Standard Deviation
  215.3  ± 48.2     203.9  ± 52.3     209.6  ± 50.6  
Fasting (non-random) serum triglyceride [1]
[units: mg/dL]
Mean ± Standard Deviation
  189.5  ± 134.0     162.0  ± 112.6     175.0  ± 126.5  
Non-HDL-C  
[units: mg/dL]
Mean ± Standard Deviation
  165.5  ± 48.5     156.8  ± 53.0     161.1  ± 50.9  
[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: Week 24 ]

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 ]

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 That Discontinued Due to Drug Related CAEs Through 24 Weeks   [ Time Frame: 24 Week last patient last visit ]

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

20.  Other Pre-specified:   Number of Patients With Drug-related Laboratory Adverse Experiences (LAEs) Through 24 Weeks   [ Time Frame: 24 Week last patient last visit ]
  Hide Outcome Measure 20

Measure Type Other Pre-specified
Measure Title Number of Patients With Drug-related Laboratory Adverse Experiences (LAEs) Through 24 Weeks
Measure Description Patients with drug-related (as assessed by an investigator who is a qualified physician, according to his/her best clinical judgement) LAEs
Time Frame 24 Week last patient last visit  
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 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]
  174     174  
Number of Patients With Drug-related Laboratory Adverse Experiences (LAEs) Through 24 Weeks  
[units: participants]
   
With LAEs     6     2  
Without LAEs     168     172  

No statistical analysis provided for Number of Patients With Drug-related Laboratory Adverse Experiences (LAEs) Through 24 Weeks



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

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

23.  Other Pre-specified:   Number of Patients That Discontinued With Drug Related LAEs Through 24 Weeks   [ Time Frame: 24 Week last patient last visit ]


  Serious Adverse Events


  Other Adverse Events


  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
The reason for early termination: Study was terminated after the primary efficacy analysis at Week 24 did not demonstrate non-inferiority of MK0518 versus KALETRA™.


  More Information