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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 1, 2015
Last verified: October 2015
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
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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: 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
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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 
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) 
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) 
[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
  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 ]

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
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Time Frame Adverse experiences that occurred after randomization and through Week 24 last patient last visit (31-Oct-2008) were collected.
Additional Description The list of Other Adverse Events has an incidence cut off of 2%, includes clinical as well laboratory Adverse Events, and does not include Serious Adverse Events.

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

Serious Adverse Events
    MK0518 400 mg b.i.d.   KALETRA™ 400/100 mg b.i.d.
Total, serious adverse events     
# participants affected / at risk   15/174 (8.62%)   10/174 (5.75%) 
Cardiac disorders     
Angina pectoris †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Ear and labyrinth disorders     
Vertigo †     
# participants affected / at risk   0/174 (0.00%)   1/174 (0.57%) 
Endocrine disorders     
Basedow's disease †     
# participants affected / at risk   0/174 (0.00%)   1/174 (0.57%) 
Eye disorders     
Ulcerative keratitis †     
# participants affected / at risk   0/174 (0.00%)   1/174 (0.57%) 
Gastrointestinal disorders     
Abdominal pain lower †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Hepatobiliary disorders     
Cholecystitis †     
# participants affected / at risk   0/174 (0.00%)   1/174 (0.57%) 
Infections and infestations     
Abdominal abscess †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Appendicitis †     
# participants affected / at risk   0/174 (0.00%)   1/174 (0.57%) 
Cellulitis †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Gastroenteritis †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Pneumonia †     
# participants affected / at risk   0/174 (0.00%)   1/174 (0.57%) 
Pneumonia staphylococcal †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Pulmonary tuberculosis †     
# participants affected / at risk   0/174 (0.00%)   1/174 (0.57%) 
Pyelonephritis acute †     
# participants affected / at risk   0/174 (0.00%)   1/174 (0.57%) 
Urinary tract infection †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Injury, poisoning and procedural complications     
Accidental overdose †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Ankle fracture †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Foreign body trauma †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Limb injury †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain †     
# participants affected / at risk   0/174 (0.00%)   1/174 (0.57%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder cancer †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Squamous cell carcinoma †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Nervous system disorders     
Cerebrospinal fistula †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Lumbar radiculopathy †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Psychiatric disorders     
Acute stress disorder †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Bipolar I disorder †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Depression †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Renal and urinary disorders     
Renal impairment †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Reproductive system and breast disorders     
Epididymitis †     
# participants affected / at risk   1/174 (0.57%)   0/174 (0.00%) 
Vascular disorders     
Vasodilatation †     
# participants affected / at risk   0/174 (0.00%)   1/174 (0.57%) 
Events were collected by systematic assessment




  Other Adverse Events


  Limitations and Caveats
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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™.


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