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

Purpose

This study will investigate the safety and efficacy of raltegravir as a therapy for Human Immunodeficiency Virus (HIV)-infected patients failing current therapy with 3-class antiviral resistance.

Condition	Intervention	Phase
HIV Infections	Drug: raltegravir potassium Drug: Comparator: placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Antiretroviral Activity of MK-0518 in Combination With an Optimized Background Therapy (OBT), Versus Optimized Background Therapy Alone, in HIV-Infected Patients With Documented Resistance to at Least 1 Drug in Each of the 3 Classes of Licensed Oral Antiretroviral Therapies

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Potassium

Drug Information available for: Potassium bicarbonate Potassium chloride Raltegravir Raltegravir potassium

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Percentage of Participants Achieving HIV RNA <400 Copies/mL at Week 16 [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
Percentage of participants who achieved HIV RNA <400 copies/mL at Week 16
Percentage of Participants Achieving HIV RNA <400 Copies/mL at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
Percentage of participants who achieved HIV RNA <400 copies/mL at Week 48
Double-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <400 Copies/mL [ Time Frame: 156 Weeks ] [ Designated as safety issue: No ]
Percentage of participants who achieved HIV RNA <400 copies/mL at Week 156
Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <400 Copies/mL [ Time Frame: 240 Weeks ] [ Designated as safety issue: No ]
Percentage of participants who achieved HIV RNA <400 Copies/mL at Week 240

Secondary Outcome Measures:

Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 16 [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
Percentage of participants who achieved HIV RNA <50 copies/mL at Week 16
Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
Percentage of participants who achieved HIV RNA <50 copies/mL at Week 48
Double-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <50 Copies/mL [ Time Frame: 156 Weeks ] [ Designated as safety issue: No ]
Percentage of participants who achieved HIV RNA <50 copies/mL at Week 156
Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <50 Copies/mL [ Time Frame: 240 Weeks ] [ Designated as safety issue: No ]
Percentage of participants who achieved HIV RNA <50 copies/mL at Week 240
Double-Blind Extension - Week 156: Percentage of Participants Without Loss of Virologic Response [ Time Frame: 156 Weeks ] [ Designated as safety issue: No ]
For participants with confirmed HIV RNA levels <50 copies/mL on 2 consecutive visits, loss of virologic response is the occurrence of the first value >50 copies/mL or loss to follow-up; participants who never achieved HIV RNA <50 copies/mL on 2 consecutive visits are also considered as having loss of virologic response. Events are the numbers of participants with loss of virologic response versus the numbers of participants with no loss of virologic response (event-free).
Change From Baseline in HIV RNA (Log 10 Copies/mL) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
Mean change from baseline at Week 16 in HIV RNA (log 10 copies/mL)
Change From Baseline in HIV RNA (log10 Copies/mL) at Week 48 [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
Mean change from baseline at Week 48 in HIV RNA (log10 copies/mL)
Double-Blind Extension - Week 156: Change From Baseline in HIV RNA (log10 Copies/mL) [ Time Frame: Baseline and Week 156 ] [ Designated as safety issue: No ]
Mean change from baseline at Week 156 in HIV RNA (log10 copies/mL)
Open-Label Extension - Week 240: Change From Baseline in HIV RNA (log10 Copies/mL) [ Time Frame: Baseline and Week 240 ] [ Designated as safety issue: No ]
Mean change from baseline at Week 240 in HIV RNA (log10 copies/mL)
Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
Mean change from baseline at Week 16 in CD4 cell count (cells/mm^3)
Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 48 [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
Mean change from baseline at Week 48 in CD4 cell count (cells/mm^3)
Double-Blind Extension - Week 156: Change From Baseline in CD4 Cell Count(Cells/mm^3) [ Time Frame: Baseline and Week 156 ] [ Designated as safety issue: No ]
Mean change from baseline at Week 156 in CD4 cell count (cells/mm^3)
Open-Label Extension - Week 240: Change From Baseline in CD4 Cell Count (Cells/mm^3) [ Time Frame: Baseline and Week 240 ] [ Designated as safety issue: No ]
Mean change from baseline at Week 240 in CD4 cell count (cells/mm^3)

Enrollment:	351
Study Start Date:	February 2006
Study Completion Date:	May 2011
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 raltegravir potassium	Drug: raltegravir potassium Raltegravir 400 mg twice daily (b.i.d.) by mouth (p.o.) with optimized background therapy. Treatment period of 48 weeks. Other Name: ISENTRESS™
Placebo Comparator: 2 Placebo	Drug: Comparator: placebo Placebo p.o. b.i.d. with optimized background therapy. Treatment period of 48 weeks.

Detailed Description:

The primary double-blind study of raltegravir versus placebo was extended to 156 weeks and was followed by an open-label raltegravir phase in which continuing participants from both the raltegravir and placebo groups received open-label raltegravir for an additional 84 weeks for a maximum duration of up to 240 weeks. Participants who had viral failure after Week 16 may have received open-label raltegravir until Week 240.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient must be HIV positive with HIV RNA values that are within ranges required by the study
Patient must have documented failure of certain antiretroviral therapy
Patient must be on the same antiretroviral therapy for at least the past two months

Exclusion Criteria:

Patient less than 16 years old
Additional study criteria will be discussed and identified by the study doctor

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00293254

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

Publications:

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.

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

Keywords provided by Merck:

Treatment Experienced

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases

Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on May 22, 2013