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

ClinicalTrials.gov Identifier:

NCT00443703

First received: March 2, 2007

Last updated: February 28, 2012

Last verified: February 2012

History of Changes

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).

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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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

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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 ]

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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 ]

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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 ]

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Measure Type	Primary
Measure Title	Mean Percent Change From Baseline in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-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]	134	135
Mean Percent Change From Baseline in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 [units: Percent Change] Mean ± Standard Deviation	-2.43 ± 22.63	2.05 ± 29.87

No statistical analysis provided for Mean Percent Change From Baseline in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-C) at 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 ]

Show Outcome Measure 6

7. Primary:

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

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8. Secondary:

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

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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 ]

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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 ]

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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 ]

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12. Secondary:

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

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13. Other Pre-specified:

Number of Patients With Serious CAEs Through 24 Weeks [ Time Frame: 24 Week last patient last visit ]

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14. Other Pre-specified:

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

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15. Other Pre-specified:

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

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16. Other Pre-specified:

Number of Patients That Died by 24 Week Last Patient Last Visit [ Time Frame: 24 Week last patient last visit ]

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17. Other Pre-specified:

Number of Patients That Discontinued Due to CAEs Through 24 Weeks [ Time Frame: 24 Week last patient last visit ]

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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 ]

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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

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

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™.

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

Publications automatically indexed to this study:

Eron JJ, Young B, Cooper DA, Youle M, Dejesus E, Andrade-Villanueva J, Workman C, Zajdenverg R, Fätkenheuer G, Berger DS, Kumar PN, Rodgers AJ, Shaughnessy MA, Walker ML, Barnard RJ, Miller MD, Dinubile MJ, Nguyen BY, Leavitt R, Xu X, Sklar P; SWITCHMRK 1 and 2 investigators. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials. Lancet. 2010 Jan 30;375(9712):396-407. Epub 2010 Jan 12.

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT00443703 History of Changes
Other Study ID Numbers:	2007_507, MK0518-032
Study First Received:	March 2, 2007
Results First Received:	October 16, 2009
Last Updated:	February 28, 2012
Health Authority:	United States: Food and Drug Administration

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