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) - Full Text View

Purpose

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 participants with suppressed viremia and impaired renal function.

Condition	Intervention	Phase
HIV Infections	Drug: Raltegravir (MK-0518) Drug: Nevirapine Drug: Lamivudine Drug: Tenofovir Drug: Emtricitabine Drug: Lopinavir Drug: Ritonavir Drug: Atazanavir Drug: Darunavir	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Switching From Regimens Consisting of a RTV-Boosted Protease Inhibitor Plus TDF/FTC to a Combination of Raltegravir Plus Nevirapine and Lamivudine in HIV Patients With Suppressed Viremia and Impaired Renal Function (RANIA Study) (Pilot Study) Protocol MK-0518-284-02

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS Kidney Tests

Drug Information available for: Proteinase inhibitor Nevirapine Lamivudine Emtricitabine Tenofovir Ritonavir Lopinavir Atazanavir Tenofovir Disoproxil Fumarate Darunavir Atazanavir sulfate Raltegravir Darunavir ethanolate Raltegravir potassium

U.S. FDA Resources

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:

Change from Baseline in estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Percentage of Participants with Suppressed Viremia (<50 copies/mL HIV-1 Ribonucleic Acid [RNA]) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Percentage of Participants with Suppressed Viremia (<50 copies/mL HIV-1 RNA) at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
Percentage of Participants with Decline in Renal Function at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]


Estimated Enrollment:	100
Study Start Date:	September 2014
Estimated Study Completion Date:	August 2017
Estimated Primary Completion Date:	August 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Raltegravir plus Nevirapine plus Lamivudine Raltegravir 400 mg oral twice daily, 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) Raltegravir (MK-0518) 400 mg tablets Drug: Nevirapine Nevirapine (NVP) 200 mg tablets Drug: Lamivudine Lamivudine (3TC) 150 mg tablets
Active Comparator: Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine 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 Tenofovir disoproxil fumarate (TDF) 300 mg tablets Drug: Emtricitabine Emtricitabine (FTC) 200 mg tablets Drug: Lopinavir Lopinavir (LPV) 200 mg tablets Drug: Ritonavir Ritonavir (r) 100 mg tablets Drug: Atazanavir Atazanavir (ATV) 300 mg tablets Drug: Darunavir Darunavir (DAR) 400 mg tablets

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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)

Exclusion Criteria:

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02116660

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators


Study Director:	Medical Director	Merck Sharp & Dohme Corp.

More Information


Responsible Party:	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:	NCT02116660 History of Changes
Other Study ID Numbers:	0518-284 2013-001637-40
Study First Received:	April 15, 2014
Last Updated:	September 6, 2016
Health Authority:	Italy: The Italian Medicines Agency

Additional relevant MeSH terms:


HIV Infections Renal Insufficiency Viremia Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Kidney Diseases Urologic Diseases Sepsis Systemic Inflammatory Response Syndrome	Inflammation Pathologic Processes Ritonavir Lopinavir Atazanavir Sulfate Darunavir HIV Protease Inhibitors Tenofovir Raltegravir Potassium Emtricitabine Lamivudine Nevirapine Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016