Clinical trial NCT02116660: 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)
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-0518-284-03
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-04-17
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline and Week 48
Secondary outcomes:
measure: Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 Ribonucleic Acid [RNA]) at Week 48
timeFrame: Week 48
measure: Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 RNA) at Week 96
timeFrame: Week 96
measure: Percentage of Participants With Decline in Renal Function at Week 48
timeFrame: Week 48
measure: Percentage of Participants With Virologic Failure (HIV-1 RNA > 50 Copies/mL)
timeFrame: Up to Week 96
measure: Change From Baseline of HIV-RNA Absolute Values
timeFrame: Baseline and Week 96
measure: Percentage of Participants With Mutations Associated With Resistance to NRTIs, NNRTIs, INI, at Virological Failure.
timeFrame: Up to Week 96
measure: Change From Baseline in Absolute CD4+ T-lymphocyte Count
timeFrame: Baseline and Week 96
measure: Percentage of Participants With Altered Liver Enzymes and Lipid Profile
timeFrame: Up to Week 96
measure: Percentage of Participants With Altered Values of Tubular Kidney Injury Markers.
timeFrame: Up to Week 96
measure: Percentage of Participants Having Changes From Baseline in Metabolic Bone Markers
timeFrame: Baseline and up to Week 96
measure: Area Under the Concentration Time Curve From Time 0 the Last Measurement Time t (AUC0-t) for Raltegravir and Nevirapine
timeFrame: Week 12: Fasted state (0 h) and 1, 2, 3, 6 and 12 h post-dose
measure: Trough Concentration (Ctrough) for Raltegravir and Nevirapine
timeFrame: Weeks 12 and 48: at the end of dosing interval at 12 h
measure: Percentage of Participants With Genotypic Resistance at Virologic Failure.
timeFrame: Up to Week 96
measure: Percentage of Participants With Adherence to Study Therapy
timeFrame: Up to Week 96
measure: Change From Baseline in Bone Disease Risk Assessment
timeFrame: Baseline and week 96
measure: Change From Baseline in the VACS Index
timeFrame: Baseline and week 96
measure: Percentage of Participants Experiencing a Decline of Renal Function
timeFrame: Up to Week 96
measure: Change From Baseline in eGFR at Week 96
timeFrame: Baseline and Week 96
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: