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)

NCT ID: NCT00369941

Last Updated: 2017-03-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

566 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-08-31

Study Completion Date

2012-02-29

Brief Summary

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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.

Detailed Description

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Conditions

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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MK-0518 400 mg b.i.d.

MK-0518 400 mg, which can be taken by mouth (PO) twice a day (b.i.d.) without regard to food, and placebo to efavirenz, which will be taken PO at bedtime (q.h.s.) on an empty stomach preferably at bedtime. All participants will take one tablet of TRUVADA® (200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) with food, daily with the morning dose of MK-0518. Dosing interval adjustment of TRUVADA® is recommended in all participants with creatinine clearance 30-49 mL/min.

Group Type EXPERIMENTAL

MK-0518

Intervention Type DRUG

400 mg MK-0518 tablet taken by mouth (PO) twice a day (b.i.d.) for up to 240 weeks

Comparator: Truvada

Intervention Type DRUG

One tablet Truvada once a day (q.d.) for up to 240 weeks (one tablet contains 200 mg emtricitabine and 300 mg tenofovir)

Comparator: Placebo to efavirenz

Intervention Type DRUG

Placebo to efavirenz PO every night (q.h.s.), taken for up to 240 weeks

Efavirenz 600 mg q.h.s.

Efavirenz 600 mg, which will be taken by mouth (PO) at bedtime (q.h.s.) on an empty stomach preferably at bedtime, and placebo to MK-0518, which will be taken PO twice a day (b.i.d.) without regard to food. All participants will take one tablet of TRUVADA® with food, daily with the morning dose of placebo. Dosing interval adjustment of TRUVADA® is recommended in all participants with creatinine clearance 30-49 mL/min.

Group Type ACTIVE_COMPARATOR

Comparator: efavirenz

Intervention Type DRUG

600 mg efavirenz tablet taken by mouth (PO) every night (q.h.s.) for up to 240 weeks

Comparator: Truvada

Intervention Type DRUG

One tablet Truvada once a day (q.d.) for up to 240 weeks (one tablet contains 200 mg emtricitabine and 300 mg tenofovir)

Comparator: Placebo to MK-0518

Intervention Type DRUG

Placebo to MK-0518 PO b.i.d., taken for up to 240 weeks

Interventions

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MK-0518

400 mg MK-0518 tablet taken by mouth (PO) twice a day (b.i.d.) for up to 240 weeks

Intervention Type DRUG

Comparator: efavirenz

600 mg efavirenz tablet taken by mouth (PO) every night (q.h.s.) for up to 240 weeks

Intervention Type 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)

Intervention Type DRUG

Comparator: Placebo to MK-0518

Placebo to MK-0518 PO b.i.d., taken for up to 240 weeks

Intervention Type DRUG

Comparator: Placebo to efavirenz

Placebo to efavirenz PO every night (q.h.s.), taken for up to 240 weeks

Intervention Type DRUG

Other Intervention Names

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raltegravir Isentress® Sustiva® emtricitabine/tenofovir disoproxil fumarate

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Monitor

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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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.

Reference Type RESULT
PMID: 19647866 (View on PubMed)

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.

Reference Type RESULT
PMID: 22849964 (View on PubMed)

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.

Reference Type RESULT
PMID: 21921224 (View on PubMed)

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.

Reference Type RESULT
PMID: 21599819 (View on PubMed)

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.

Reference Type RESULT
PMID: 21522004 (View on PubMed)

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.

Reference Type RESULT
PMID: 21434946 (View on PubMed)

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.

Reference Type RESULT
PMID: 21198432 (View on PubMed)

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.

Reference Type RESULT
PMID: 20404738 (View on PubMed)

Other Identifiers

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MK-0518-021

Identifier Type: OTHER

Identifier Source: secondary_id

2006_519

Identifier Type: OTHER

Identifier Source: secondary_id

0518-021

Identifier Type: -

Identifier Source: org_study_id

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