MK0518 in the Treatment of HIV-Infected Patients Switched From a Protease Inhibitor Regimen (0518-032)(TERMINATED)

A Multicenter, Double-Blind, Randomized, Active-Controlled Study to Evaluate the Safety and Antiretroviral Activity of MK0518 Versus KALETRA in HIV-Infected Patients Switched From a Stable KALETRA-Based Regimen - Study A

The purpose of this study is to investigate the efficacy, safety, and tolerability of an investigational treatment for patients with HIV.

Study Overview

• Status: Terminated
• Conditions: HIV Infection
• Intervention / Treatment: Drug: MK0518 (raltegravir); Drug: Comparator: placebo; Drug: Comparator: placebo; Drug: Comparator: KALETRA™ (lopinavir (+) ritonavir )

• Study Type: Interventional
• Enrollment (Actual): 352
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient is at least 18 years of age
• Patient is Human Immunodeficiency Virus (HIV) positive
• Patient has documented Human Immunodeficiency Virus (HIV) RiboNucleic Acid (RNA) <50 copies/milliliter (mL) for at least 3 months while on a KALETRA based regimen
• Patient has been on a KALETRA based regimen for at least 3 months without a change in background antiretroviral therapy
• Patient has no documentation of HIV RNA >50 copies/mL for at least 3 months while on the KALETRA based regimen

Exclusion Criteria:

• Patient is or plans to become pregnant, or nursing a child
• Patient plans to donate eggs or impregnate/donate sperm
• Patient is receiving Stavudine (d4T) as a component of the background antiretroviral therapy
• Patient is currently receiving a second protease inhibitor in addition to KALETRA
• Patient is currently receiving, or has received in the past twelve weeks, treatment for the management of elevated lipids
• Patient has used another experimental HIV-integrase inhibitor
• Patient has a current (active) diagnosis of acute hepatitis due to any cause
• Patient has used systemic immunosuppressive therapy within one month prior to treatment in this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Arm 1: MK0518 (raltegravir) + placebo to KALETRA™ (lopinavir (+) ritonavir )	Drug: MK0518 (raltegravir); MK0518 (raltegravir) 400 mg by mouth (PO) twice daily (b.i.d) for up to 48 weeks of treatment; Other Names: raltegravir; MK0518; Drug: Comparator: placebo; MK0518 (raltegravir) 400 mg by mouth (PO) twice daily (b.i.d.) Placebo for up to 48 weeks of treatment; Drug: Comparator: placebo; KALETRA™ (lopinavir (+) ritonavir ) 400/100 mg by mouth (PO) twice daily (b.i.d.) Placebo for up to 48 weeks of treatment.
Active Comparator: 2; Arm 2: KALETRA™ (lopinavir (+) ritonavir) + placebo to MK0518 (raltegravir)	Drug: Comparator: placebo; MK0518 (raltegravir) 400 mg by mouth (PO) twice daily (b.i.d.) Placebo for up to 48 weeks of treatment; Drug: Comparator: placebo; KALETRA™ (lopinavir (+) ritonavir ) 400/100 mg by mouth (PO) twice daily (b.i.d.) Placebo for up to 48 weeks of treatment.; Drug: Comparator: KALETRA™ (lopinavir (+) ritonavir ); KALETRA™ (lopinavir (+) ritonavir ) 400/100 mg by mouth (PO) twice daily (b.i.d.) for up to 48 weeks of treatment.; Other Names: KALETRA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Plasma Human Immunodeficiency Virus (HIV) RiboNucleic Acid (RNA) <50 Copies/mL at Week 24		Week 24
Number of Patients With Clinical Adverse Experiences (CAEs) Through 24 Weeks	An adverse experience 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 (Merck & Co., Inc.) product, whether or not considered related to the use of the product	24 Week last patient last visit
Mean Percent Change From Baseline in Fasting Serum Cholesterol at Week 12		Baseline and Week 12
Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12		Baseline and Week 12
Mean Percent Change From Baseline in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12		Baseline and Week 12
Mean Percent Change From Baseline in Fasting Serum High-Density Lipoprotein Cholesterol (HDL-C) at Week 12		Baseline and Week 12
Median Percent Change From Baseline in Serum Triglyceride at Week 12	Standard Deviation (Robust): calculated as interquartile range (IQR)/1.075, where IQR=3rd quartile-1st quartile.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change From Baseline in Fasting Serum Cholesterol at Week 24		Baseline and Week 24
Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24		Baseline and Week 24
Mean Percent Change From Baseline in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24		Baseline and Week 24
Mean Percent Change From Baseline in Fasting Serum High-Density Lipoprotein Cholesterol (HDL-C) at Week 24		Baseline and Week 24
Median Percent Change From Baseline in Serum Triglyceride at Week 24	Standard Deviation (Robust): calculated as interquartile range (IQR)/1.075, where IQR=3rd quartile-1st quartile.	Baseline and Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Serious CAEs Through 24 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	24 Week last patient last visit
Number of Patients With Drug-related CAEs Through 24 Weeks	Patients with drug-related (as assessed by an investigator who is a qualified physician, according to his/her best clinical judgement) CAEs.	24 Week last patient last visit
Number of Patients With Serious Drug-related CAEs Through 24 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 judgement	24 Week last patient last visit
Number of Patients That Died by 24 Week Last Patient Last Visit		24 Week last patient last visit
Number of Patients That Discontinued Due to CAEs Through 24 Weeks		24 Week last patient last visit
Number of Patients That Discontinued Due to Drug Related CAEs Through 24 Weeks		24 Week last patient last visit
Number of Patients With Laboratory Adverse Experiences (LAEs) Through 24 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 (Merck & Co., Inc.) product, whether or not considered related to the use of the product	24 Week last patient last visit
Number of Patients With Drug-related Laboratory Adverse Experiences (LAEs) Through 24 Weeks	Patients with drug-related (as assessed by an investigator who is a qualified physician, according to his/her best clinical judgement) LAEs	24 Week last patient last visit
Number of Patients With Serious LAEs Through 24 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	24 Week last patient last visit
Number of Patients That Discontinued Due to LAEs Through 24 Weeks		24 Week last patient last visit
Number of Patients That Discontinued With Drug Related LAEs Through 24 Weeks	Number of patients that discontinued with drug-related (as assessed by an investigator who is a qualified physician, according to his or her clinical judgement) LAEs.	24 Week last patient last visit

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Eron JJ, Young B, Cooper DA, Youle M, Dejesus E, Andrade-Villanueva J, Workman C, Zajdenverg R, Fatkenheuer 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. doi: 10.1016/S0140-6736(09)62041-9. Epub 2010 Jan 12.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: March 2, 2007
• First Submitted That Met QC Criteria: March 5, 2007
• First Posted (Estimate): March 6, 2007

Study Record Updates

• Last Update Posted (Actual): March 21, 2017
• Last Update Submitted That Met QC Criteria: February 14, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: treatment experienced
• 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; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Raltegravir Potassium; Ritonavir; Lopinavir
• Other Study ID Numbers: 0518-032; 2007_507

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php