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

Purpose

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

Condition	Intervention	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


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:	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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Lamivudine Tenofovir Efavirenz Tenofovir Disoproxil Fumarate Raltegravir Raltegravir potassium

U.S. FDA Resources

Further study details as provided by Merck Sharp & Dohme Corp.:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
Number of Patients With Clinical Adverse Experiences (CAEs) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Change From Baseline in Plasma HIV RNA at Week 24 (Cohort II) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Change From Baseline in Plasma HIV RNA at Week 96 [ Time Frame: Baseline and Week 96 ] [ Designated as safety issue: No ]
Change From Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline and Week 96 ] [ Designated as safety issue: No ]
Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 240 [ Time Frame: Week 240 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Number of Patients With Drug-related CAEs [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
Number of Patients With Laboratory Adverse Experiences (LAEs) [ Time Frame: 48 Weeks ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]


Enrollment:	206
Study Start Date:	January 2005
Study Completion Date:	July 2010
Primary Completion Date:	October 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Study First Received:	December 22, 2004
Results First Received:	January 21, 2010
Last Updated:	September 26, 2014
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes Immune System Diseases Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Virus Diseases Efavirenz Lamivudine	Tenofovir Tenofovir disoproxil Anti-HIV Agents Anti-Infective Agents Anti-Retroviral Agents Antiviral Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors Pharmacologic Actions Reverse Transcriptase Inhibitors Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015