A Study to Determine the Safety and Efficacy of Once Daily Raltegravir Compared to Twice Daily Raltegravir (MK-0518-071)

A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Study the Safety and Efficacy of Once Daily Raltegravir (MK0518) Versus Twice Daily Raltegravir, Each in Combination With TRUVADA™, in Treatment-Naïve HIV Infected Patients

A study to evaluate the safety, tolerability and efficacy of once daily Raltegravir compared to twice daily raltegravir when each is given in combination with TRUVADA™ in treatment-naïve human immunodeficiency virus (HIV)-infected patients.

Study Overview

• Status: Terminated
• Conditions: HIV
• Intervention / Treatment: Drug: Comparator: Raltegravir 400 mg b.i.d.; Drug: TRUVADA™; Drug: Experimental: Raltegravir 800 mg q.d.

Detailed Description

Following the 96-week double-blind study period (MK0518-071)(NCT00745823), subjects may enroll in an extension study (MK0518-071-10)(NCT00745823). From weeks 96 to 120, subjects' treatment assignments will remain as in the base study.

From week 120 to 240, all subjects will receive open-label raltegravir (800 mg, once daily) in combination with TRUVADA™.

• Study Type: Interventional
• Enrollment (Actual): 775
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient is male or female 18 years of age or older
• Patient is HIV positive
• Patient is naïve to antiretroviral therapy (ART) or has received less than 7 days total of any ART

Extension Study:

• The planned extension study did not take place as the study was terminated after the Week 48 analysis.

Exclusion Criteria:

• Patient is a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence
• Patient has documented resistance to tenofovir or emtricitabine
• Patient is currently participating or has participated in a study with an investigational compound or device within 45 days of signing informed consent
• Patient is pregnant or breastfeeding, or expecting to conceive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Raltegravir 400 mg b.i.d.	Drug: Comparator: Raltegravir 400 mg b.i.d.; Raltegravir 400 mg tablet by mouth (PO) twice daily (b.i.d.) + two raltegravir placebo tablets + one tablet of TRUVADA™ once daily (q.d.); Other Names: ISENTRESS™; Drug: TRUVADA™; One tablet TRUVADA™ q.d. (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate)
Experimental: Raltegravir 800 mg q.d.	Drug: TRUVADA™; One tablet TRUVADA™ q.d. (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate); Drug: Experimental: Raltegravir 800 mg q.d.; Raltegravir 800 mg tablet PO q.d. + two raltegravir placebo tablets + one tablet TRUVADA™ q.d.; Other Names: ISENTRESS™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks	Week 48
Number of Participants With One or More Adverse Events at 48 Weeks	Week 48
Number of Participants Who Discontinued Due to an Adverse Event at 48 Weeks	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With HIV Ribonucleic Acid (RNA) <400 Copies/mL at 48 Weeks		48 weeks
Mean Change From Baseline to Week 48 in CD4 Cell Count		Baseline and Week 48
Number of Participants With HIV RNA <50 Copies/mL at 96 Weeks	As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.	Week 96
Number of Participants With HIV RNA <400 Copies/mL at 96 Weeks	As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.	Week 96
Mean Change From Baseline to Week 96 in CD4 Cell Count	As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.	Baseline and Week 96
Number of Participants With One or More Adverse Events at 96 Weeks	As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.	Week 96
Number of Participants Who Discontinued Due to an Adverse Event at 96 Weeks	As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.	Week 96

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Eron JJ Jr, Rockstroh JK, Reynes J, Andrade-Villanueva J, Ramalho-Madruga JV, Bekker LG, Young B, Katlama C, Gatell-Artigas JM, Arribas JR, Nelson M, Campbell H, Zhao J, Rodgers AJ, Rizk ML, Wenning L, Miller MD, Hazuda D, DiNubile MJ, Leavitt R, Isaacs R, Robertson MN, Sklar P, Nguyen BY; QDMRK Investigators. Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial. Lancet Infect Dis. 2011 Dec;11(12):907-15. doi: 10.1016/S1473-3099(11)70196-7. Epub 2011 Sep 18. Erratum In: Lancet Infect Dis. 2011 Dec;11(12):895. Dosage error in article text.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: September 2, 2008
• First Submitted That Met QC Criteria: September 2, 2008
• First Posted (Estimate): September 3, 2008

Study Record Updates

• Last Update Posted (Actual): March 21, 2017
• Last Update Submitted That Met QC Criteria: February 14, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: HIV Infections; Treatment Naïve
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: 0518-071; 2008_543 (Other Identifier: Merck Registration Number); CTRI/2009/091/000145 (Registry Identifier: CTRI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php