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MK0518 in the Treatment of HIV-Infected Patients Switched From a Protease Inhibitor Regimen (0518-032)(TERMINATED)

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ClinicalTrials.gov Identifier: NCT00443703
Recruitment Status : Terminated (primary efficacy analysis at Week 24 did not demonstrate non-inferiority of raltegravir versus lopinavir (+) ritonavir)
First Posted : March 6, 2007
Results First Posted : December 1, 2009
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 Infection
Interventions: Drug: MK0518 (raltegravir)
Drug: Comparator: KALETRA™ (lopinavir (+) ritonavir )
Drug: Comparator: placebo

  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

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 
Overall Participants Analyzed 
[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) 
Sex: Female, Male 
[Units: Participants]
Count of Participants 		     
Female      28  16.1%      45  25.9%      73  21.0% 
Male      146  83.9%      129  74.1%      275  79.0% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants 		     
Hispanic or Latino      25  14.4%      23  13.2%      48  13.8% 
Not Hispanic or Latino      149  85.6%      151  86.8%      300  86.2% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants 		     
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0% 
Asian      2   1.1%      3   1.7%      5   1.4% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0% 
Black or African American      24  13.8%      28  16.1%      52  14.9% 
White      146  83.9%      141  81.0%      287  82.5% 
More than one race      2   1.1%      2   1.1%      4   1.1% 
Unknown or Not Reported      0   0.0%      0   0.0%      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) 
[1] Standard Deviation (Robust): calculated as interquartile range (IQR)/1.075, where IQR=3rd quartile-1st quartile.
Non-HDL-C 
[Units: mg/dL]
Mean (Standard Deviation) 		 165.5  (48.5)   156.8  (53.0)   161.1  (50.9) 


  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 ]
  Show Outcome Measure 1

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

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

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 ]
  Show Outcome Measure 4

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 ]
  Show Outcome Measure 5

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 ]
  Show Outcome Measure 6

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

Measure Type Primary
Measure Title Median Percent Change From Baseline in Serum Triglyceride at Week 12
Measure Description Standard Deviation (Robust): calculated as interquartile range (IQR)/1.075, where IQR=3rd quartile-1st quartile.
Time Frame Baseline and Week 12  

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. 
Participants Analyzed 
[Units: Participants]
 		 142   146 
Median Percent Change From Baseline in Serum Triglyceride at Week 12 
[Units: Percent Change]
Median (Standard Deviation) 		 -41.50  (35.37)   3.56  (59.36) 

No statistical analysis provided for Median Percent Change From Baseline in Serum Triglyceride at Week 12



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

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 ]
  Show Outcome Measure 9

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 ]
  Show Outcome Measure 10

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 ]
  Show Outcome Measure 11

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

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

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

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

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

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

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 ]
  Show Outcome Measure 18

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

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 ]
  Show Outcome Measure 20

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

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

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


  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
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