A Study to Evaluate the Safety and Efficacy of Raltegravir (MK0518) in HIV-Infected Patients Failing Current Antiretroviral Therapies (0518-019 EXT2)

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Merck

ClinicalTrials.gov Identifier:

NCT00293254

First received: February 15, 2006

Last updated: May 14, 2012

Last verified: May 2012

History of Changes

Results First Received: August 20, 2009

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	HIV Infections
Interventions:	Drug: raltegravir potassium 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 3; First Patient In: 08-Mar-2006; Last Patient Last Visit (LPLV) for Week 48: 31-Jul-2007; Extension Study LPLV Week 240: May 2011 53 sites (US, Brazil, Canada, Colombia, Mexico, and Puerto Rico).

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

Phase 3; First Patient In: 08-Mar-2006; Last Patient Last Visit (LPLV) for Week 48: 31-Jul-2007; Extension Study LPLV Week 240: May 2011

53 sites (US, Brazil, Canada, Colombia, Mexico, and Puerto Rico).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients failed prior antiretroviral therapy (HIV RNA >1000 copies/mL), and had documented resistance to at least one drug in each class of licensed oral antiretroviral therapy (Nucleoside Reverse Transcriptase inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, and Protease Inhibitors). All patients must have met laboratory criteria.

Reporting Groups

	Description
Raltegravir 400 mg b.i.d. + OBT	No text entered.
Placebo + OBT	No text entered.

Participant Flow for 4 periods

Period 1: Primary Study - Double-Blind Week 0-48

	Raltegravir 400 mg b.i.d. + OBT	Placebo + OBT
STARTED	232	119
Treated	230	119
Continuing in Double-Blind	177 ^[1]	55 ^[2]
COMPLETED	177	55
NOT COMPLETED	55	64
Never Treated	2	0
Adverse Event	2	1
Death	5	2
Lack of Efficacy	2	2
Lost to Follow-up	3	1
Withdrawal by Subject	5	1
Moved or trial terminated at site	1	0
Entered OLPVF Phase	35	57

[1]	Excludes participants who entered the Open-Label Post-Virologic Failure (OLPVF) Phase
[2]	Excludes participants who entered the OLPVF phase

Period 2: Extension - Double-Blind Week 49-156

	Raltegravir 400 mg b.i.d. + OBT	Placebo + OBT
STARTED	177	54 ^[1]
COMPLETED	120	25
NOT COMPLETED	57	29
Adverse Event	4	1
Death	4	1
Lack of Efficacy	3	4
Lost to Follow-up	3	3
Withdrawal by Subject	12	8
Participant Moved/Site Stopped Trial	6	3
Other Reason	10	2
Entered OLPVF Phase	15	7

[1]	1 of 55 participants who completed Week 48 did not enter the extension study.

Period 3: Extension - Open-Label Week 157-240

	Raltegravir 400 mg b.i.d. + OBT	Placebo + OBT
STARTED	120	19 ^[1]
COMPLETED	110	18
NOT COMPLETED	10	1
Adverse Event	2	1
Lack of Efficacy	1	0
Withdrawal by Subject	1	0
Lost to Follow-up	2	0
Other Reason	4	0

[1]	6 of 25 participants who completed the double-blind phase did not enter this open-label phase.

Period 4: Open-Label Post Virologic Failure Phase

	Raltegravir 400 mg b.i.d. + OBT	Placebo + OBT
STARTED	50 ^[1]	64 ^[1]
COMPLETED	19	37
NOT COMPLETED	31	27
Adverse Event	4	7
Lack of Efficacy	16	14
Withdrawal by Subject	6	3
Lost to Follow-up	3	0
Participant Moved/Site Stopped Trial	1	1
Other Reason	1	2

[1]	Number of participants who failed treatment and consented to enter the OLPVF phase

Baseline Characteristics

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Reporting Groups

	Description
Raltegravir 400 mg b.i.d. + OBT	No text entered.
Placebo + OBT	No text entered.
Total	Total of all reporting groups

Baseline Measures

	Raltegravir 400 mg b.i.d. + OBT	Placebo + OBT	Total
Number of Participants [units: participants]	230	119	349
Age [units: Years] Mean ( Full Range )	45.3 ( 16 to 67 )	46.5 ( 17 to 70 )	45.7 ( 16 to 70 )
Gender [units: participants]
Female	20	12	32
Male	210	107	317
Race/Ethnicity, Customized [units: Participants]
White	127	77	204
Black	47	21	68
Asian	2	1	3
Hispanic	47	18	65
Native American	1	0	1
Other	6	2	8
Cluster of Differentiation 4 (CD4) Cell Count [units: cells/mm^3] Mean ( Full Range )	146 ( 1 to 757 )	163 ( 0 to 674 )	152 ( 0 to 757 )
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) [units: copies/mL] Geometric Mean ( Full Range )	49159 ( 200 to 750000 )	47850 ( 200 to 750000 )	48709 ( 200 to 750000 )

Outcome Measures

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1. Primary:

Percentage of Participants Achieving HIV RNA <400 Copies/mL at Week 16 [ Time Frame: 16 Weeks ]

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2. Primary:

Percentage of Participants Achieving HIV RNA <400 Copies/mL at Week 48 [ Time Frame: 48 Weeks ]

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3. Primary:

Double-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <400 Copies/mL [ Time Frame: 156 Weeks ]

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4. Primary:

Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <400 Copies/mL [ Time Frame: 240 Weeks ]

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5. Secondary:

Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 16 [ Time Frame: 16 Weeks ]

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Measure Type	Secondary
Measure Title	Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 16
Measure Description	Percentage of participants who achieved HIV RNA <50 copies/mL at Week 16
Time Frame	16 Weeks
Safety Issue	No

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
Raltegravir 400 mg b.i.d. + OBT	No text entered.
Placebo + OBT	No text entered.

Measured Values

	Raltegravir 400 mg b.i.d. + OBT	Placebo + OBT
Number of Participants Analyzed [units: participants]	229	119
Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 16 [units: Percentage of Participants] Number ( 95% Confidence Interval )	62.0 ( 55.4 to 68.3 )	36.1 ( 27.5 to 45.4 )

No statistical analysis provided for Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 16

6. Secondary:

Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 48 [ Time Frame: 48 Weeks ]

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7. Secondary:

Double-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <50 Copies/mL [ Time Frame: 156 Weeks ]

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8. Secondary:

Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <50 Copies/mL [ Time Frame: 240 Weeks ]

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9. Secondary:

Double-Blind Extension - Week 156: Percentage of Participants Without Loss of Virologic Response [ Time Frame: 156 Weeks ]

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10. Secondary:

Change From Baseline in HIV RNA (Log 10 Copies/mL) at Week 16 [ Time Frame: Baseline and Week 16 ]

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11. Secondary:

Change From Baseline in HIV RNA (log10 Copies/mL) at Week 48 [ Time Frame: Baseline and Week 48 ]

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12. Secondary:

Double-Blind Extension - Week 156: Change From Baseline in HIV RNA (log10 Copies/mL) [ Time Frame: Baseline and Week 156 ]

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13. Secondary:

Open-Label Extension - Week 240: Change From Baseline in HIV RNA (log10 Copies/mL) [ Time Frame: Baseline and Week 240 ]

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14. Secondary:

Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 16 [ Time Frame: Baseline and Week 16 ]

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15. Secondary:

Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 48 [ Time Frame: Baseline and Week 48 ]

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16. Secondary:

Double-Blind Extension - Week 156: Change From Baseline in CD4 Cell Count(Cells/mm^3) [ Time Frame: Baseline and Week 156 ]

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17. Secondary:

Open-Label Extension - Week 240: Change From Baseline in CD4 Cell Count (Cells/mm^3) [ Time Frame: Baseline and Week 240 ]

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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
Adverse events are reported by original treatment group for the entire 240-week study, including double-blind, open-label, and OLPVF phases; 83 of 119 participants in the placebo group also received raltegravir in the open-label or OLPVF phase.

Results Point of Contact:

Name/Title: Executive Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com

Publications of Results:

Steigbigel RT, Cooper DA, Teppler H, Eron JJ, Gatell JM, Kumar PN, Rockstroh JK, Schechter M, Katlama C, Markowitz M, Yeni P, Loutfy MR, Lazzarin A, Lennox JL, Clotet B, Zhao J, Wan H, Rhodes RR, Strohmaier KM, Barnard RJ, Isaacs RD, Nguyen BY; BENCHMRK Study Teamsa. Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials. Clin Infect Dis. 2010 Feb 15;50(4):605-12.

Other Publications:

Steigbigel RT, Cooper DA, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Nguyen BY, Teppler H; BENCHMRK Study Teams. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):339-54.

Cooper DA, Steigbigel RT, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Teppler H, Nguyen BY; BENCHMRK Study Teams. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):355-65.

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT00293254 History of Changes
Other Study ID Numbers:	MK-0518-019, 2005_097
Study First Received:	February 15, 2006
Results First Received:	August 20, 2009
Last Updated:	May 14, 2012
Health Authority:	United States: Food and Drug Administration

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