Evaluation of Renal Function, Efficacy, and Safety When Switching From Tenofovir/Emtricitabine Plus a Protease Inhibitor/Ritonavir, to a Combination of Raltegravir (MK-0518) Plus Nevirapine Plus Lamivudine in HIV-1 Participants With Suppressed Viremia and Impaired Renal Function (MK-0518-284)

NCT02116660 | Terminated Phase 2 Results

• 3 other identifiers: 0518-2842013-001637-40MK-0518-284
• Study Type: interventional
• Target: 11
• Locations: 0 countries
• Sites: N/A

Brief Summary

To evaluate changes in renal function, efficacy, and safety when switching from a combination of tenofovir/emtricitabine (TDF/FTC) plus a protease inhibitor/ritonavir (PI/r) to a combination of raltegravir (MK-0518) plus nevirapine plus lamivudine in human immunodeficiency virus (HIV)-1 infected participants with suppressed viremia and impaired renal function.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)

  Glomerular Filtration Rate (eGFR) was estimated from the Modification of Diet in Renal Disease (MDRD)-6 equation. The MDRD-6 equation = 198 × \[serum creatinine(mg/dL)\]\^-0.858 × \[age\]-0.167 × \[0.822 if patient is female\] × \[1.178 if patient is black\] × \[serum urea nitrogen concentration (mg/dL)\]\^-0.293 × \[urine urea nitrogen excretion (g/d)\]\^0.249.

  Baseline and Week 48

Secondary Outcomes (18)

• Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 Ribonucleic Acid [RNA]) at Week 48

  Week 48

• Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 RNA) at Week 96

  Week 96

• Percentage of Participants With Decline in Renal Function at Week 48

  Week 48

• Percentage of Participants With Virologic Failure (HIV-1 RNA > 50 Copies/mL)

  Up to Week 96

• Change From Baseline of HIV-RNA Absolute Values

  Baseline and Week 96

Study Arms (2)

Raltegravir plus Nevirapine plus Lamivudine

EXPERIMENTAL

Raltegravir 400 mg oral twice daily for 96 weeks; plus nevirapine 200 mg oral once daily for 14 days followed by nevirapine 200 mg oral twice daily, plus lamivudine 150 mg oral twice daily for 96 weeks

Drug: Raltegravir (MK-0518); Drug: Nevirapine; Drug: Lamivudine

Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine

ACTIVE COMPARATOR

Tenofovir/emtricitabine 300/200 mg oral once daily plus 1) lopinavir/ritonavir 400/100 mg oral twice daily or 800/200 mg oral once daily, or 2) atazanavir/ritonavir 300/100 mg oral once daily, or 3) darunavir/ritonavir 800/100 mg oral once daily or 600/100 mg oral twice daily

Drug: Tenofovir; Drug: Emtricitabine; Drug: Lopinavir; Drug: Ritonavir; Drug: Atazanavir; Drug: Darunavir

Interventions

Raltegravir (MK-0518) DRUG

Raltegravir (MK-0518) 400 mg tablets

Raltegravir plus Nevirapine plus Lamivudine

Nevirapine DRUG

Nevirapine (NVP) 200 mg tablets

Raltegravir plus Nevirapine plus Lamivudine

Lamivudine DRUG

Lamivudine (3TC) 150 mg tablets

Raltegravir plus Nevirapine plus Lamivudine

Tenofovir DRUG

Tenofovir disoproxil fumarate (TDF) 300 mg tablets

Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine

Emtricitabine DRUG

Emtricitabine (FTC) 200 mg tablets

Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine

Lopinavir DRUG

Lopinavir (LPV) 200 mg tablets

Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine

Ritonavir DRUG

Ritonavir (r) 100 mg tablets

Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine

Atazanavir DRUG

Atazanavir (ATV) 300 mg tablets

Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine

Darunavir DRUG

Darunavir (DAR) 400 mg tablets

Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine

Eligibility Criteria

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

You may qualify if:

• Male, or non-pregnant, non-breastfeeding female
• No previous history of virological failure
• No previous exposure to non-nucleoside reverse transcriptase inhibitors or integrase inhibitors
• No previous history of intolerance to lamivudine
• At least 2 documented plasma HIV-1 RNA \<50 copies/mL and no HIV-1 \>50 copies/mL in the 12 months before screening
• Receiving the same protease inhibitor/ritonavir plus tenofovir/emtricitabine combination for at least the 6 months before screening
• Has no major International Antiviral Society (IAS)-USA mutations on genotype testing performed before starting antiretroviral treatment
• Sexually-active participants and their partners of child-bearing potential agree to use a medically acceptable method of contraception from 2 weeks before Day 1 and for at least 6 months after the last dose of study drug (postmenopausal women are not required to use contraception; sexually-active male participants with a female partner of child-bearing potential must provide written informed consent to information regarding any pregnancy)

You may not qualify if:

• Positive for hepatitis B surface antigen (HBsAg+) or anticipated need for hepatitis C virus treatment
• Liver cirrhosis
• Has a history of diabetes mellitus, defined as initiation of antidiabetic treatment or verification of diabetes in a case report form
• Has any cancer, excluding stable Kaposi Sarcoma
• Allergy or sensitivity to the investigational product or excipients
• Female participant who is nursing
• Female participant who is pregnant or intends to become pregnant
• Has an active Acquired Immunodeficiency Syndrome (AIDS)-defining event except stable Kaposi Sarcoma or HIV Wasting Syndrome
• Received any investigational drug within 30 days before screening
• Participated in any other clinical trial within 30 days before signing informed consent for the current trial

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

HIV Infections

Interventions

Raltegravir Potassium; Nevirapine; Lamivudine; Tenofovir; Emtricitabine; Lopinavir; Ritonavir; Atazanavir Sulfate; Darunavir

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; Pyridines; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrimidinones; Thiazoles; Sulfur Compounds; Azoles; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Sulfonamides; Amides; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Furans

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 Director

  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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2014
• First Posted: April 17, 2014
• Study Start: September 3, 2014
• Primary Completion: July 10, 2017
• Study Completion: July 10, 2017
• Last Updated: April 8, 2019
• Results First Posted: April 8, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share