A Study to Evaluate the Safety and Efficacy of an Investigational Drug in HIV Infected Patients (0518-004)(COMPLETED)

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ClinicalTrials.gov Identifier: NCT00100048

Recruitment Status : Completed

First Posted : December 23, 2004

Results First Posted : March 29, 2010

Last Update Posted : September 9, 2015

Sponsor:

Information provided by (Responsible Party):

Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

This is a study that will investigate the safety and efficacy of an investigational drug in Human immunodeficiency virus (HIV) infected patients.

Condition or disease	Intervention/treatment	Phase
HIV Infections Acquired Immunodeficiency Syndrome	Drug: Comparator: MK0518 monotherapy Drug: Comparator: MK0518 combination therapy Drug: Comparator: efavirenz Drug: Comparator: tenofovir Drug: Comparator: lamivudine Drug: Placebo monotherapy	Phase 2

Detailed Description:

Participants who completed 48 weeks of the original 48-week double-blind study were invited to continue in two extensions: MK0518-004-10 (NCT00100048), which extended the study to 144 weeks, and MK0518-004-20 (NCT00100048), which extended the study to 240 weeks. Participants who had been randomized to MK0518 in the base study continued at 400 mg MK0518 twice daily.

Participants randomized to efavirenz in the base study continued to receive efavirenz at the dosage given in the base study. The doses of open label tenofovir and lamivudine continued unchanged.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	206 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	Multicenter, Double-Blind, Randomized, Dose Ranging Study to Compare the Safety and Activity of MK0518 Plus Tenofovir and Lamivudine (3TC) Versus Efavirenz Plus Tenofovir and Lamivudine (3TC) in ART-Naive, HIV-Infected Patients
Study Start Date :	January 2005
Actual Primary Completion Date :	October 2006
Actual Study Completion Date :	July 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 600 mg monotherapy MK0518 600 mg twice daily	Drug: Comparator: MK0518 monotherapy MK0518 twice daily for 10 days
Experimental: 400 mg monotherapy MK0518 400 mg twice daily	Drug: Comparator: MK0518 monotherapy MK0518 twice daily for 10 days
Experimental: 200 mg monotherapy MK0518 200 mg twice daily	Drug: Comparator: MK0518 monotherapy MK0518 twice daily for 10 days
Experimental: 100 mg monotherapy MK0518 100 mg twice daily	Drug: Comparator: MK0518 monotherapy MK0518 twice daily for 10 days
Placebo Comparator: placebo monotherapy Placebo to MK0518 twice daily	Drug: Placebo monotherapy Placebo to MK0518 twice daily
Experimental: 600 mg combo therapy MK0518 600 mg + tenofovir + lamivudine	Drug: Comparator: MK0518 combination therapy MK0518 twice daily for 48 weeks Drug: Comparator: tenofovir tenofovir 300 mg daily for 48 weeks Drug: Comparator: lamivudine lamivudine 300 mg daily for 48 weeks
Experimental: 400 mg combo therapy MK0518 400 mg + tenofovir + lamivudine	Drug: Comparator: MK0518 combination therapy MK0518 twice daily for 48 weeks Drug: Comparator: tenofovir tenofovir 300 mg daily for 48 weeks Drug: Comparator: lamivudine lamivudine 300 mg daily for 48 weeks
Experimental: 200 mg combo therapy MK0518 200 mg + tenofovir + lamivudine	Drug: Comparator: MK0518 combination therapy MK0518 twice daily for 48 weeks Drug: Comparator: tenofovir tenofovir 300 mg daily for 48 weeks Drug: Comparator: lamivudine lamivudine 300 mg daily for 48 weeks
Experimental: 100 mg combo therapy MK0518 100 mg + tenofovir + lamivudine	Drug: Comparator: MK0518 combination therapy MK0518 twice daily for 48 weeks Drug: Comparator: tenofovir tenofovir 300 mg daily for 48 weeks Drug: Comparator: lamivudine lamivudine 300 mg daily for 48 weeks
Active Comparator: EFV combo therapy efavirenz + tenofovir + lamivudine	Drug: Comparator: efavirenz efavirenz 600 mg every night at bedtime for 48 weeks Drug: Comparator: tenofovir tenofovir 300 mg daily for 48 weeks Drug: Comparator: lamivudine lamivudine 300 mg daily for 48 weeks

Outcome Measures

Primary Outcome Measures :

Change From Baseline in Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) on Day 10 (Cohort I) [ Time Frame: Baseline and Day 10 ]
Mean change from baseline on Day 10 in plasma Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) (copies/mL)
Number of Patients With Clinical Adverse Experiences (CAEs) and Number of Patients With Serious CAEs at Day 10 (Cohort I) [ Time Frame: 10 days ]
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.

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.
Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 24 (Cohort II) [ Time Frame: Week 24 ]
Number of Patients With Clinical Adverse Experiences (CAEs) [ Time Frame: 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.
Number of Patients With Serious CAEs (Cohort I and II Combined) [ Time Frame: 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
Number of Patients With Serious CAEs and Non-serious CAEs at Week 144 [ Time Frame: 144 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

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
Number of Participants With Clinical Adverse Experiences (AEs)and Serious Adverse Experiences (SAEs) [ Time Frame: Week 240 ]
An AE was defined as any unfavorable & unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to its use. Any worsening of a preexisting condition which was temporally associated with the use of the study drug, was also an AE.

A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was cancer, or was an overdose.
Number of Participants With HIV RNA (Human Immunodeficiency Virus Ribonucleic Acid) Levels Below 50 Copies/mL at Week 240 [ Time Frame: Week 240 ]
HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ UltraSensitive Assay.

Secondary Outcome Measures :

Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II) [ Time Frame: Week 24 ]
Change From Baseline in Plasma HIV RNA at Week 24 (Cohort II) [ Time Frame: Baseline and Week 24 ]
Mean change from baseline at Week 24 in plasma HIV RNA (copies/mL)
Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 (Cohort II) [ Time Frame: Baseline and Week 24 ]
Mean change from baseline at Week 24 in CD4 Cell Count (cells/mm3)
Number of Patients With HIV RNA Level Below 50 Copies/mL and HIV RNA Level Below 400 Copies/mL at Week 96 [ Time Frame: 96 Weeks ]
Change From Baseline in Plasma HIV RNA at Week 96 [ Time Frame: Baseline and Week 96 ]
Change From Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline and Week 96 ]
Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 240 [ Time Frame: Week 240 ]
HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ Standard Assay.
Change From Baseline in Plasma HIV RNA at Week 240 [ Time Frame: Baseline and Week 240 ]
HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ Standard Assay.
Change From Baseline in CD4 (T-helper) Cell Count at Week 240 [ Time Frame: Baseline and Week 240 ]
Change in number of CD4 cells/mm^3 from baseline to Week 240.

Other Outcome Measures:

Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 48 [ Time Frame: 48 weeks ]
Number of Patients With Drug-related CAEs [ Time Frame: 48 weeks ]
Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs
Number of Patients With Serious Drug-related CAEs [ Time Frame: 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.
Number of Patients That Discontinued With CAEs [ Time Frame: 48 Weeks ]
Number of Patients With Laboratory Adverse Experiences (LAEs) [ Time Frame: 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
Number of Patients With Serious LAEs [ Time Frame: 48 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
Number of Patients With Drug-related LAEs [ Time Frame: 48 Weeks ]
Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) LAEs
Number of Patients With Serious Drug-related LAEs [ Time Frame: 48 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
Number of Patients That Discontinued With LAEs [ Time Frame: 48 Weeks ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient must be HIV positive who must have received less than 7 days total of any antiretroviral therapy (HIV related therapy)

Extension Studies:

First extension: Patient completed the 48-week base study
Second extension: Patient completed the first 144-week extension study

Exclusion Criteria:

Less than 18 years of age
Individuals who currently do not test positive for HIV

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00100048

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators


Study Director:	Medical Monitor	Merck Sharp & Dohme Corp.

More Information

Publications:

Markowitz M, Morales-Ramirez JO, Nguyen BY, Kovacs CM, Steigbigel RT, Cooper DA, Liporace R, Schwartz R, Isaacs R, Gilde LR, Wenning L, Zhao J, Teppler H. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):509-15. Erratum in: J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):492.

Murray JM, Emery S, Kelleher AD, Law M, Chen J, Hazuda DJ, Nguyen BY, Teppler H, Cooper DA. Antiretroviral therapy with the integrase inhibitor raltegravir alters decay kinetics of HIV, significantly reducing the second phase. AIDS. 2007 Nov 12;21(17):2315-21.

Markowitz M, Nguyen BY, Gotuzzo E, Mendo F, Ratanasuwan W, Kovacs C, Prada G, Morales-Ramirez JO, Crumpacker CS, Isaacs RD, Gilde LR, Wan H, Miller MD, Wenning LA, Teppler H; Protocol 004 Part II Study Team. Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr. 2007 Oct 1;46(2):125-33.

Markowitz M, Nguyen BY, Gotuzzo E, Mendo F, Ratanasuwan W, Kovacs C, Prada G, Morales-Ramirez JO, Crumpacker CS, Isaacs RD, Campbell H, Strohmaier KM, Wan H, Danovich RM, Teppler H; Protocol 004 Part II Study Team. Sustained antiretroviral effect of raltegravir after 96 weeks of combination therapy in treatment-naive patients with HIV-1 infection. J Acquir Immune Defic Syndr. 2009 Nov 1;52(3):350-6. doi: 10.1097/QAI.0b013e3181b064b0.


Responsible Party:	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:	NCT00100048 History of Changes
Other Study ID Numbers:	0518-004 2004_096
First Posted:	December 23, 2004 Key Record Dates
Results First Posted:	March 29, 2010
Last Update Posted:	September 9, 2015
Last Verified:	September 2015

Additional relevant MeSH terms:


HIV Infections Immunologic Deficiency Syndromes Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immune System Diseases Slow Virus Diseases Tenofovir Lamivudine Efavirenz Raltegravir Potassium	Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 CYP2B6 Inducers Cytochrome P-450 Enzyme Inducers Cytochrome P-450 CYP3A Inducers HIV Integrase Inhibitors

HIV Infections
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immune System Diseases
Slow Virus Diseases
Tenofovir
Lamivudine
Efavirenz
Raltegravir Potassium

Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers
HIV Integrase Inhibitors

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