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:

Merck

ClinicalTrials.gov Identifier:

NCT00443729

First received: March 2, 2007

Last updated: April 9, 2013

Last verified: April 2013

History of Changes

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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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

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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: 24 Weeks ]

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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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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 ]

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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 ]

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 ]

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Measure Type	Other Pre-specified
Measure Title	Number of Patients That Died by 24 Week Last Patient Last Visit
Measure Description	No text entered.
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]	176	178
Number of Patients That Died by 24 Week Last Patient Last Visit [units: Participants]
Died	0	0
Did Not Die	176	178

No statistical analysis provided for Number of Patients That Died by 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 ]

Show Outcome Measure 17

18. 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 18

19. Other Pre-specified:

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

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20. Other Pre-specified:

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

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21. Other Pre-specified:

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

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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
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:	Executive Vice President, Clinical and Quantitative Sciences, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00443729 History of Changes
Other Study ID Numbers:	2007_508, MK0518-033
Study First Received:	March 2, 2007
Results First Received:	October 12, 2009
Last Updated:	April 9, 2013
Health Authority:	United States: Food and Drug Administration

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