Safety and Efficacy of an Investigational Drug in Human Immunodeficiency Virus (HIV)-Infected Patients Failing Current Antiretroviral Therapies (0518-005)(COMPLETED)

Multicenter Study to Evaluate the Safety and Efficacy of MK0518 in Combination With An Optimized Background Therapy (OBT), Versus OBT Alone, in HIV-Infected Patients With Documented Resistance

This study will investigate the safety and efficacy of different doses of an investigational drug (MK0518) as a therapy for HIV-infected patients failing current antiretroviral therapies.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Acquired Immunodeficiency Syndrome
• Intervention / Treatment: Drug: Comparator: MK0518; Drug: MK0518; Drug: MK0518; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient must be HIV positive with Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) values that are within ranges required by the study
• Patient must be currently on antiretroviral therapy (ART)

Exclusion Criteria:

• Patient less than 18 years of age
• Additional exclusion criteria will be discussed and identified by the study doctor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 4; Placebo	Drug: Placebo; Placebo to MK0518, oral tablet b.i.d, for 24 weeks
Experimental: 1; MK0518 200 mg	Drug: Comparator: MK0518; MK0518 oral tablets 200 mg b.i.d, for 24 weeks; Other Names: MK0518
Experimental: 2; MK0518 400 mg	Drug: MK0518; MK0518 oral tablets 400 mg b.i.d, for 24 weeks; Drug: MK0518; MK0518 oral tablets 600 mg b.i.d, for 24 weeks
Experimental: 3; MK0518 600 mg	Drug: MK0518; MK0518 oral tablets 400 mg b.i.d, for 24 weeks; Drug: MK0518; MK0518 oral tablets 600 mg b.i.d, for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma HIV RNA (log10 Copies/mL) at Week 24	Mean change from baseline at Week 24 in HIV RNA (log10 copies/mL) in all patients	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Virologic Responses at Week 24	Number of patients who achieve HIV RNA <400 copies/mL; HIV RNA level <50 copies/mL at Week 24; or reduction from baseline in HIV RNA (log10 copies/mL) exceeding 1.0 log10 copies/mL at Week 24; at Week 24	24 weeks
Change From Baseline in CD4 Cell Count at Week 24	Mean change from baseline at Week 24 in CD4 Cell Count (cells/mm3)	Baseline and Week 24
Number of Patients With Clinical Adverse Experiences (CAEs) at 48 Weeks	An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product	48 weeks
Number of Patients With Serious CAEs at 48 Weeks	Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose	48 weeks
Number of Patients With Drug-related CAEs at 48 Weeks	Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs	48 weeks
Number of Patients With Serious Drug-related CAEs at 48 Weeks	Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose. Drug-related are as assessed by an investigator who is a qualified physician according to his/her best clinical judgment.	48 weeks
Number of Patients That Died by 48 Weeks		48 weeks
Number of Patients That Discontinued With CAEs at 48 Weeks		48 weeks
Number of Patients That Discontinued With Drug-related CAEs at 48 Weeks		48 weeks
Number of Patients That Discontinued With Serious CAEs at 48 Weeks		48 weeks
Number of Patients That Discontinued With Serious Drug-related CAEs at 48 Weeks		48 weeks
Number of Patients With Laboratory Adverse Experiences (LAEs) at 48 Weeks	A laboratory adverse experience (LAE) is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product	48 weeks
Number of Patients With Drug-related LAEs at 48 Weeks	Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) LAEs	48 weeks
Number of Patients Discontinued With Laboratory Adverse Experiences (LAEs) at 48 Weeks		48 weeks
Number of Patients Discontinued With Drug-related LAEs at 48 Weeks		48 weeks
Number of Patients With Clinical Adverse Experiences (CAEs) at 96 Weeks	An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product	96 weeks
Number of Patients With Serious CAEs at 96 Weeks	Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose	96 weeks
Number of Patients With Drug-related CAEs at 96 Weeks	Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs	96 weeks
Number of Patients With Serious Drug-related CAEs at 96 Weeks	Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose. Drug-related are as assessed by an investigator who is a qualified physician according to his/her best clinical judgment.	96 weeks
Number of Patients That Died by 96 Weeks		96 weeks
Number of Patients That Discontinued With CAEs at 96 Weeks		96 weeks
Number of Patients That Discontinued With Drug-related CAEs at 96 Weeks		96 weeks
Number of Patients That Discontinued With Serious CAEs at 96 Weeks		96 weeks
Number of Patients That Discontinued With Serious Drug-related CAEs at 96 Weeks		96 weeks
Number of Patients With Laboratory Adverse Experiences (LAEs) at 96 Weeks	A laboratory adverse experience (LAE) is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product	96 weeks
Number of Patients With Drug-related LAEs at 96 Weeks	Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) LAEs	96 weeks
Number of Patients Discontinued With Laboratory Adverse Experiences (LAEs) at 96 Weeks		96 weeks
Number of Patients Discontinued With Drug-related LAEs at 96 Weeks		96 weeks
Number of Patients With Clinical Adverse Experiences (CAEs) at 168 Weeks	An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product	168 weeks
Number of Patients With Serious CAEs at 168 Weeks	Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose	168 weeks
Number of Patients With Drug-related CAEs at 168 Weeks	Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs	168 weeks
Number of Patients With Serious Drug-related CAEs at 168 Weeks	Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose. Drug-related are as assessed by an investigator who is a qualified physician according to his/her best clinical judgment.	168 weeks
Number of Patients That Died by 168 Weeks		168 weeks
Number of Patients That Discontinued With CAEs at 168 Weeks		168 weeks
Number of Patients That Discontinued With Drug-related CAEs at 168 Weeks		168 weeks
Number of Patients That Discontinued With Serious CAEs at 168 Weeks		168 weeks
Number of Patients That Discontinued With Serious Drug-related CAEs at 168 Weeks		168 weeks
Number of Patients With Laboratory Adverse Experiences (LAEs) at 168 Weeks	A laboratory adverse experience (LAE) is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product	168 weeks
Number of Patients With Serious LAEs at 168 Weeks	Serious LAEs are any LAEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose	168 weeks
Number of Patients Discontinued With Drug-related LAEs at 168 Weeks		168 weeks
Number of Patients With Drug-related LAEs at 168 Weeks	Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) LAEs	168 weeks
Number of Patients With Serious Drug-related LAEs at 168 Weeks	Serious LAEs are any LAEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose	168 weeks
Number of Patients Discontinued With LAEs at 168 Weeks		168 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma HIV RNA (log10 Copies/mL) at Week 168 in Combined Substudies	Mean change from baseline at Week 168 in HIV RNA (log10 copies/mL) in patients from combined substudies in the double-blind plus open-label phases.	Baseline and Week 168
Change From Baseline in CD4 Cell Count at Week 168 in Combined Substudies	Mean change from baseline at Week 168 in CD4 Cell Count (cells/mm3) in patients from combined substudies in the double-blind plus open-label phases.	Baseline and Week 168

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Grinsztejn B, Nguyen BY, Katlama C, Gatell JM, Lazzarin A, Vittecoq D, Gonzalez CJ, Chen J, Harvey CM, Isaacs RD; Protocol 005 Team. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet. 2007 Apr 14;369(9569):1261-1269. doi: 10.1016/S0140-6736(07)60597-2.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): October 1, 2006
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: March 8, 2005
• First Submitted That Met QC Criteria: March 8, 2005
• First Posted (Estimate): March 9, 2005

Study Record Updates

• Last Update Posted (Estimate): December 4, 2015
• Last Update Submitted That Met QC Criteria: December 3, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium
• Other Study ID Numbers: 0518-005; MK0518-005; 2005_007