Clinical trial NCT00369941: A Study to Evaluate the Safety and Antiretroviral Activity of MK-0518 Versus Efavirenz in Treatment Naive HIV-Infected Patients, Each in Combination With TRUVADA (0518-021 EXT)
Official title: A Multicenter, Double-Blind, Randomized, Active-Controlled Study to Evaluate the Safety and Antiretroviral Activity of MK-0518 Versus Efavirenz in Treatment Naive HIV-Infected Patients, Each in Combination With TRUVADA™
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2006-08-30
Enrollment: 566
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will investigate the safety and efficacy of MK-0518 versus efavirenz, in combination with TRUVADA, as a therapy for Human Immunodeficiency Virus (HIV)-infected patients not previously treated.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* Participant has received approved or experimental antiretroviral agents in the past
* Participant 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)
* Participant has documented resistance to tenofovir, emtricitabine, and/or efavirenz
* Participant has used another experimental HIV-integrase inhibitor
* Participant has a current (active) diagnosis of acute hepatitis due to any cause
* Participants with chronic hepatitis including chronic hepatitis B and/or C may enter the study as long as they have stable liver function tests

Primary outcomes:
measure: Number of Participants Who Achieved Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
timeFrame: 48 Weeks
measure: Number of Participants With Clinical Adverse Experiences (CAEs) at Week 48
timeFrame: 48 Weeks
measure: Number of Participants With Serious CAEs at Week 48
timeFrame: 48 Weeks
measure: Number of Participants With Drug-related CAEs at Week 48
timeFrame: 48 Weeks
measure: Number of Participants With Serious Drug-related CAEs at Week 48
timeFrame: 48 Weeks
measure: Number of Participants That Died by Week 48
timeFrame: 48 Weeks
measure: Number of Participants That Discontinued With CAEs at Week 48
timeFrame: 48 Weeks
measure: Number of Participants That Discontinued With Serious CAEs at Week 48
timeFrame: 48 Weeks
measure: Number of Participants That Discontinued With Drug-related CAEs at Week 48
timeFrame: 48 Weeks
measure: Number of Participants That Discontinued With Serious Drug-related CAEs at Week 48
timeFrame: 48 Weeks
measure: Number of Participants With Laboratory Adverse Experiences (LAEs) at Week 48
timeFrame: 48 Weeks
measure: Number of Participants With Serious LAEs at Week 48
timeFrame: 48 Weeks
measure: Number of Participants With Drug-related LAEs at Week 48
timeFrame: 48 Weeks
measure: Number of Participants With Serious Drug-related LAEs at Week 48
timeFrame: 48 Weeks
measure: Number of Participants Discontinued With LAEs at Week 48
timeFrame: 48 Weeks
measure: Number of Participants Discontinued With Drug-related LAEs at Week 48
timeFrame: 48 Weeks
Secondary outcomes:
measure: Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 48
timeFrame: 48 Weeks
measure: Change From Baseline in Cluster of Differentiation Antigen 4 (CD4) Cell Count at Week 48
timeFrame: Baseline and Week 48
measure: Number of Participants Who Achieved HIV RNA <50 Copies/mL at Week 96
timeFrame: 96 Weeks
measure: Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 96
timeFrame: 96 Weeks
measure: Change From Baseline in CD4 Cell Count at Week 96
timeFrame: Baseline and Week 96
measure: Number of Participants Who Achieved HIV RNA <50 Copies/mL at Week 156
timeFrame: 156 Weeks
measure: Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 156
timeFrame: 156 Weeks
measure: Change From Baseline in CD4 Cell Count at Week 156
timeFrame: Baseline and Week 156
measure: Number of Participants Who Achieved HIV RNA <50 Copies/mL at Week 240
timeFrame: 240 Weeks
measure: Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 240
timeFrame: 240 Weeks
measure: Change From Baseline in CD4 Cell Count at Week 240
timeFrame: Baseline and Week 240
measure: Number of Participants With Nervous System Symptoms Assessed by Review of Accumulated Safety Data up to Week 8
timeFrame: 8 Weeks
measure: Number of Participants With CAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants With CAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants With CAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants With Serious CAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants With Serious CAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants With Serious CAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants With Drug-related CAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants With Drug-related CAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants With Drug-related CAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants With Serious Drug-related CAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants With Serious Drug-related CAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants With Serious Drug-related CAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants That Died by Week 96
timeFrame: 96 Weeks
measure: Number of Participants That Died by Week 156
timeFrame: 156 Weeks
measure: Number of Participants That Died by Week 240
timeFrame: 240 Weeks
measure: Number of Participants That Discontinued With CAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants That Discontinued With CAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants That Discontinued With CAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants That Discontinued With Drug-related CAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants That Discontinued With Drug-related CAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants That Discontinued With Drug-related CAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants That Discontinued With Serious CAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants That Discontinued With Serious CAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants That Discontinued With Serious CAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants That Discontinued With Serious Drug-related CAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants That Discontinued With Serious Drug-related CAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants That Discontinued With Serious Drug-related CAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants With LAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants With LAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants With LAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants With Drug-related LAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants With Drug-related LAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants With Drug-related LAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants With Serious LAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants With Serious LAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants With Serious LAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants With Serious Drug-related LAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants With Serious Drug-related LAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants With Serious Drug-related LAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants Discontinued With LAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants Discontinued With LAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants Discontinued With LAEs at Week 240
timeFrame: 240 Weeks
measure: Number of Participants Discontinued With Drug-related LAEs at Week 96
timeFrame: 96 Weeks
measure: Number of Participants Discontinued With Drug-related LAEs at Week 156
timeFrame: 156 Weeks
measure: Number of Participants Discontinued With Drug-related LAEs at Week 240
timeFrame: 240 Weeks
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1016/S0140-6736(09)60918-1. Epub 2009 Aug 3.
citation: DeJesus E, Rockstroh JK, Lennox JL, Saag MS, Lazzarin A, Zhao J, Wan H, Rodgers AJ, Walker ML, Miller M, DiNubile MJ, Nguyen BY, Teppler H, Leavitt R, Sklar P; STARTMRK Investigators. Efficacy of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: week-192 overall and subgroup analyses from STARTMRK. HIV Clin Trials. 2012 Jul-Aug;13(4):228-32. doi: 10.1310/hct1304-228.
citation: 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. doi: 10.1093/cid/cir510.
citation: Rockstroh J, Teppler H, Zhao J, Sklar P, Harvey C, Strohmaier K, Leavitt R, Nguyen BY. Safety and efficacy of raltegravir in patients with HIV-1 and hepatitis B and/or C virus coinfection. HIV Med. 2012 Feb;13(2):127-31. doi: 10.1111/j.1468-1293.2011.00933.x. Epub 2011 May 22.
citation: Rockstroh JK, Teppler H, Zhao J, Sklar P, Miller MD, Harvey CM, Strohmaier KM, Leavitt RY, Nguyen BY. Clinical efficacy of raltegravir against B and non-B subtype HIV-1 in phase III clinical studies. AIDS. 2011 Jul 17;25(11):1365-9. doi: 10.1097/QAD.0b013e328348065a.
citation: Nguyen BY, Isaacs RD, Teppler H, Leavitt RY, Sklar P, Iwamoto M, Wenning LA, Miller MD, Chen J, Kemp R, Xu W, Fromtling RA, Vacca JP, Young SD, Rowley M, Lower MW, Gottesdiener KM, Hazuda DJ. Raltegravir: the first HIV-1 integrase strand transfer inhibitor in the HIV armamentarium. Ann N Y Acad Sci. 2011 Mar;1222:83-9. doi: 10.1111/j.1749-6632.2011.05972.x.
citation: Teppler H, Brown DD, Leavitt RY, Sklar P, Wan H, Xu X, Lievano F, Lehman HP, Mast TC, Nguyen BY. Long-term safety from the raltegravir clinical development program. Curr HIV Res. 2011 Jan;9(1):40-53. doi: 10.2174/157016211794582650.
citation: Lennox JL, Dejesus E, Berger DS, Lazzarin A, Pollard RB, Ramalho Madruga JV, Zhao J, Wan H, Gilbert CL, Teppler H, Rodgers AJ, Barnard RJ, Miller MD, Dinubile MJ, Nguyen BY, Leavitt R, Sklar P; STARTMRK Investigators. Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses. J Acquir Immune Defic Syndr. 2010 Sep;55(1):39-48. doi: 10.1097/QAI.0b013e3181da1287.