A Study to Evaluate the Safety and Antiretroviral Activity of MK0518 Versus Efavirenz in Treatment Naive HIV-Infected Patients, Each in Combination With TRUVADA (0518-021) - Full Text View

Sponsor:	Merck
Information provided by (Responsible Party):	Merck
ClinicalTrials.gov Identifier:	NCT00369941

Purpose

This study will investigate the safety and efficacy of MK0518 versus efavirenz, in combination with TRUVADA, as a therapy for Human immunodeficiency virus (HIV)-infected patients not previously treated.

Condition	Intervention	Phase
HIV Infections	Drug: MK0518 Drug: Comparator: efavirenz Drug: Comparator: Truvada Drug: Comparator: Placebo to MK0518 Drug: Comparator: Placebo to efavirenz	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, Active-Controlled Study to Evaluate the Safety and Antiretroviral Activity of MK0518 Versus Efavirenz in Treatment Naive HIV-Infected Patients, Each in Combination With TRUVADA

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Efavirenz Raltegravir Truvada Raltegravir potassium

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Number of Patients Who Achieved HIV RNA <50 Copies/mL at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of Patients Who Achieved HIV RNA <400 Copies/mL at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
Change From Baseline in CD4 Cell Count 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/mm3)
Number of Patients Who Achieved HIV RNA Level <50 Copies/mL and HIV RNA <400 Copies/mL at Week 96 [ Time Frame: 96 Weeks ] [ Designated as safety issue: No ]
Antiretroviral activity was evaluated for patients who achieved HIV RNA level <50 copies/mL and HIV RNA <400 copies/mL at Week 96 .
Change From Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline and Week 96 ] [ Designated as safety issue: No ]
Mean change from baseline at Week 96 in CD4 Cell Count (cells/mm3)
Number of Patients With Nervous System Symptoms Assessed by Review of Accumulated Safety Data up to Week 8 [ Time Frame: 8 Weeks ] [ Designated as safety issue: Yes ]
Patients with dizziness, insomnia, somnolence, concentration impaired, depression, nightmare, confusional state, suicidal ideation, nervous system disorder, psychotic disorder, abnormal dreams, suicide attempt, acute psychodsis, delirum, depressed level of consciousness, hallucination, auditory hallucination, completed suicide, and major depression
Number of Patients With Clinical Adverse Experiences (CAEs) at 96 Weeks [ Time Frame: 96 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 at 96 Weeks [ Time Frame: 96 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 Drug-related CAEs at 96 Weeks [ Time Frame: 96 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 at 96 Weeks [ Time Frame: 96 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 Died by 96 Weeks [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]
Number of Patients That Discontinued With CAEs at 96 Weeks [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]
Number of Patients That Discontinued With Drug-related CAEs at 96 Weeks [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]
Number of Patients That Discontinued With Serious CAEs at 96 Weeks [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]
Number of Patients That Discontinued With Serious Drug-related CAEs at 96 Weeks [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]
Number of Patients With Laboratory Adverse Experiences (LAEs) at 96 Weeks [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]
Number of Patients With Drug-related LAEs at 96 Weeks [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]
Number of Patients With Serious LAEs at 96 Weeks [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]
Number of Patients Discontinued With Laboratory Adverse Experiences (LAEs) at 96 Weeks [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]
Number of Patients Discontinued With Drug-related LAEs at 96 Weeks [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]

Enrollment:	566
Study Start Date:	August 2006
Study Completion Date:	February 2012
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group 1 MK0518 + placebo to efavirenz + Truvada	Drug: MK0518 400 mg MK0518 tablet taken by mouth (PO) Twice a day (b.i.d.) for up to 240 weeks Other Name: MK0518 Drug: Comparator: Truvada one tablet Truvada once a day (q.d.) for up to 240 weeks (one tablet contains 200 mg emtricitabine and 300 mg tenofovir) Other Name: Truvada Drug: Comparator: Placebo to efavirenz placebo to efavirenz PO q.h.s., taken for up to 240 weeks
Active Comparator: Group 2 efavirenz + placebo to MK0518 + Truvada	Drug: Comparator: efavirenz 600 mg efavirenz tablet taken by Mouth (PO) every night (q.h.s.) for up to 240 weeks Other Name: efavirenz Drug: Comparator: Truvada one tablet Truvada once a day (q.d.) for up to 240 weeks (one tablet contains 200 mg emtricitabine and 300 mg tenofovir) Other Name: Truvada Drug: Comparator: Placebo to MK0518 placebo to MK0518 PO b.i.d., taken for up to 240 weeks

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient is a male or female at least 18 years of age
Patient is HIV positive
Patient is naïve to antiretroviral therapy (ART) and has not received any ART

Exclusion Criteria:

Patient has received approved or experimental antiretroviral agents in the past
Patient has been treated for a viral infection other than HIV such as hepatitis B virus infection with an agent that is active against HIV including but not limited to adefovir or lamivudine (= 7 days total)
Patient has documented resistance to tenofovir, emtricitabine, and/or efavirenz
Patient has used another experimental HIV-integrase inhibitor
Patient has a current (active) diagnosis of acute hepatitis due to any cause
Patients with chronic hepatitis including chronic hepatitis B and/or C may enter the study as long as they have stable liver function tests

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00369941

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

Publications:

Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, Berger DS, Zhao J, Xu X, Williams-Diaz A, Rodgers AJ, Barnard RJ, Miller MD, DiNubile MJ, Nguyen BY, Leavitt R, Sklar P; STARTMRK investigators. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009 Sep 5;374(9692):796-806. Epub 2009 Aug 3.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rockstroh JK, Lennox JL, Dejesus E, Saag MS, Lazzarin A, Wan H, Walker ML, Xu X, Zhao J, Teppler H, Dinubile MJ, Rodgers AJ, Nguyen BY, Leavitt R, Sklar P; STARTMRK Investigators. Long-term treatment with raltegravir or efavirenz combined with tenofovir/emtricitabine for treatment-naive human immunodeficiency virus-1-infected patients: 156-week results from STARTMRK. Clin Infect Dis. 2011 Oct;53(8):807-16.

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT00369941 History of Changes
Other Study ID Numbers:	2006_519, MK0518-021
Study First Received:	August 29, 2006
Results First Received:	September 18, 2009
Last Updated:	March 9, 2012
Health Authority:	United States: Food and Drug Administration

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

Efavirenz
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on May 22, 2012