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)

NCT00369941 | Completed Phase 3 Results

• 3 other identifiers: 0518-021MK-0518-0212006_519
• Study Type: interventional
• Target: 566
• Locations: 0 countries
• Sites: N/A

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (16)

• Number of Participants Who Achieved Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) <50 Copies/mL at Week 48

  Antiretroviral activity was evaluated for participants who achieved HIV RNA level \<50 copies/mL at Week 48.

  48 Weeks

• Number of Participants With Clinical Adverse Experiences (CAEs) at Week 48

  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 study drug, whether or not considered related to the use of the product.

  48 Weeks

• Number of Participants With Serious CAEs at Week 48

  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.

  48 Weeks

• Number of Participants With Drug-related CAEs at Week 48

  Adverse experiences (AEs) in this study were defined as "drug-related" if the investigator, who is a qualified physician, considered the AE as possibly, probably, or definitely related to MK-0518 or efavirenz alone or in combination with TRUVADA® or to TRUVADA® alone according to his/her best clinical judgment.

  48 Weeks

• Number of Participants With Serious Drug-related CAEs at Week 48

  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. Adverse experiences (AEs) in this study were defined as "drug-related" if the investigator, who is a qualified physician, considered the AE as possibly, probably, or definitely related to MK-0518 or efavirenz alone or in combination with TRUVADA® or to TRUVADA® alone according to his/her best clinical judgment.

  48 Weeks

• Number of Participants That Died by Week 48

  All participant deaths in the span of 48 weeks on study were recorded.

  48 Weeks

• Number of Participants That Discontinued With CAEs at Week 48

  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 study drug, whether or not considered related to the use of the product.

  48 Weeks

• Number of Participants That Discontinued With Serious CAEs at Week 48

  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.

  48 Weeks

• Number of Participants That Discontinued With Drug-related CAEs at Week 48

  Adverse experiences (AEs) in this study were defined as "drug-related" if the investigator, who is a qualified physician, considered the AE as possibly, probably, or definitely related to MK-0518 or efavirenz alone or in combination with TRUVADA® or to TRUVADA® alone according to his/her best clinical judgment.

  48 Weeks

• Number of Participants That Discontinued With Serious Drug-related CAEs at Week 48

  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. Adverse experiences (AEs) in this study were defined as "drug-related" if the investigator, who is a qualified physician, considered the AE as possibly, probably, or definitely related to MK-0518 or efavirenz alone or in combination with TRUVADA® or to TRUVADA® alone according to his/her best clinical judgment.

  48 Weeks

• Number of Participants With Laboratory Adverse Experiences (LAEs) at Week 48

  A laboratory AE is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product.

  48 Weeks

• Number of Participants With Serious LAEs at Week 48

  A laboratory AE is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Serious AEs 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.

  48 Weeks

• Number of Participants With Drug-related LAEs at Week 48

  A laboratory AE is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Adverse experiences (AEs) in this study were defined as "drug-related" if the investigator, who is a qualified physician, considered the AE as possibly, probably, or definitely related to MK-0518 or efavirenz alone or in combination with TRUVADA® or to TRUVADA® alone according to his/her best clinical judgment.

  48 Weeks

• Number of Participants With Serious Drug-related LAEs at Week 48

  A laboratory AE is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Serious AEs 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. Adverse experiences (AEs) in this study were defined as "drug-related" if the investigator, who is a qualified physician, considered the AE as possibly, probably, or definitely related to MK-0518 or efavirenz alone or in combination with TRUVADA® or to TRUVADA® alone according to his/her best clinical judgment.

  48 Weeks

• Number of Participants Discontinued With LAEs at Week 48

  A laboratory AE is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product.

  48 Weeks

• Number of Participants Discontinued With Drug-related LAEs at Week 48

  A laboratory AE is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Adverse events (AEs) in this study were defined as "drug-related" if the investigator considered the AE as possibly, probably, or definitely related to MK-0518 or efavirenz alone or in combination with TRUVADA® or to TRUVADA® alone.

  48 Weeks

Secondary Outcomes (57)

• Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 48

  48 Weeks

• Change From Baseline in Cluster of Differentiation Antigen 4 (CD4) Cell Count at Week 48

  Baseline and Week 48

• Number of Participants Who Achieved HIV RNA <50 Copies/mL at Week 96

  96 Weeks

• Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 96

  96 Weeks

• Change From Baseline in CD4 Cell Count at Week 96

  Baseline and Week 96

Study Arms (2)

MK-0518 400 mg b.i.d.

EXPERIMENTAL

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.

Drug: MK-0518; Drug: Comparator: Truvada; Drug: Comparator: Placebo to efavirenz

Efavirenz 600 mg q.h.s.

ACTIVE COMPARATOR

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.

Drug: Comparator: efavirenz; Drug: Comparator: Truvada; Drug: Comparator: Placebo to MK-0518

Interventions

MK-0518 DRUG

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

Also known as: raltegravir, Isentress®

MK-0518 400 mg b.i.d.

Comparator: efavirenz DRUG

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

Also known as: Sustiva®

Efavirenz 600 mg q.h.s.

Comparator: Truvada DRUG

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

Also known as: emtricitabine/tenofovir disoproxil fumarate

Efavirenz 600 mg q.h.s.; MK-0518 400 mg b.i.d.

Comparator: Placebo to MK-0518 DRUG

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

Efavirenz 600 mg q.h.s.

Comparator: Placebo to efavirenz DRUG

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

MK-0518 400 mg b.i.d.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (8)

• 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.

  PMID: 19647866 RESULT

• 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.

  PMID: 22849964 RESULT

• 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.

  PMID: 21921224 RESULT

• 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.

  PMID: 21599819 RESULT

• 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.

  PMID: 21522004 RESULT

• 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.

  PMID: 21434946 RESULT

• 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.

  PMID: 21198432 RESULT

• 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.

  PMID: 20404738 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Raltegravir Potassium; efavirenz; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2006
• First Posted: August 30, 2006
• Study Start: August 1, 2006
• Primary Completion: May 1, 2009
• Study Completion: February 1, 2012
• Last Updated: March 21, 2017
• Results First Posted: May 11, 2010

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will share