Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02116660
Other study ID # 0518-284
Secondary ID 2013-001637-40MK
Status Terminated
Phase Phase 2
First received
Last updated
Start date September 3, 2014
Est. completion date July 10, 2017

Study information

Verified date April 2019
Source Merck Sharp & Dohme Corp.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Terminated
Enrollment 11
Est. completion date July 10, 2017
Est. primary completion date July 10, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Raltegravir (MK-0518)
Raltegravir (MK-0518) 400 mg tablets
Nevirapine
Nevirapine (NVP) 200 mg tablets
Lamivudine
Lamivudine (3TC) 150 mg tablets
Tenofovir
Tenofovir disoproxil fumarate (TDF) 300 mg tablets
Emtricitabine
Emtricitabine (FTC) 200 mg tablets
Lopinavir
Lopinavir (LPV) 200 mg tablets
Ritonavir
Ritonavir (r) 100 mg tablets
Atazanavir
Atazanavir (ATV) 300 mg tablets
Darunavir
Darunavir (DAR) 400 mg tablets

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 Ribonucleic Acid [RNA]) at Week 48 Plasma was to be collected at Week 48 in order to quantify HIV-1 RNA. and identify the percentage of participants with <50 copies/mL HIV-1 RNA. Week 48
Secondary Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 RNA) at Week 96 Plasma was to be collected at Week 96 in order to quantify HIV-1 RNA. and identify the percentage of participants with <50 copies/mL HIV-1 RNA. Week 96
Secondary Percentage of Participants With Decline in Renal Function at Week 48 Decline in renal function was to be assessed by evaluating MDRD-6, creatinine clearance and serum phosphate. Week 48
Secondary Percentage of Participants With Virologic Failure (HIV-1 RNA > 50 Copies/mL) Plasma was to be collected up to Week 96 in order to quantify HIV-1 RNA, and identify the percentage of participants with >50 copies/mL HIV-1 RNA. Up to Week 96
Secondary Change From Baseline of HIV-RNA Absolute Values Plasma was to be collected at baseline and Week 96 in order to determine the change from baseline in HIV-1 RNA. Baseline and Week 96
Secondary Percentage of Participants With Mutations Associated With Resistance to NRTIs, NNRTIs, INI, at Virological Failure. Participants were to be identified with mutations associated with Nucleoside/ Nucleotide Reverse Transcriptase Inhibitors (NRTIs), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), and Integrase Inhibitor (INI). Virological failure is defined as 2 consecutive plasma HIV-1 RNA >200 copies/mL at least two weeks apart while on previous or current ARV therapy. Up to Week 96
Secondary Change From Baseline in Absolute CD4+ T-lymphocyte Count Cluster of Differentiation 4 + (CD4+) T-lymphocyte cell counts were to be determined at baseline and Week 96, in order to determine the change from baseline. Baseline and Week 96
Secondary Percentage of Participants With Altered Liver Enzymes and Lipid Profile Values of liver enzymes and lipids were to be determined from laboratory tests, in order to identify the percentage of participants classified with altered values. Up to Week 96
Secondary Percentage of Participants With Altered Values of Tubular Kidney Injury Markers. Values of tubular kidney injury markers. were to be determined, in order to identify the percentage of participants classified with altered values. Up to Week 96
Secondary Percentage of Participants Having Changes From Baseline in Metabolic Bone Markers Changes from baseline in metabolic bone markers, serum Bone Specific Alkaline Phosphatase (s-BSAP) and C-telopeptides of type 1 Collagen (s-CTx), were to be determined, in order to classify the percentage of participants with changes. Baseline and up to Week 96
Secondary Area Under the Concentration Time Curve From Time 0 the Last Measurement Time t (AUC0-t) for Raltegravir and Nevirapine Blood samples were to be collected in Week 12 in order to use the trapezoidal method to determine the AUC0-t of Raltegravir and Nevirapine Week 12: Fasted state (0 h) and 1, 2, 3, 6 and 12 h post-dose
Secondary Trough Concentration (Ctrough) for Raltegravir and Nevirapine Blood samples were to be collected in Weeks 12 and 48 in order to use the trapezoidal method to determine the Ctrough, the lowest concentration reached by the drug before the next dose is administered, of Raltegravir and Nevirapine. Weeks 12 and 48: at the end of dosing interval at 12 h
Secondary Percentage of Participants With Genotypic Resistance at Virologic Failure. Genotypic resistance measures the presence of particular HIV-1 mutations that give rise to drug resistance. Virological failure is defined as 2 consecutive plasma HIV-1 RNA >200 copies/mL at least two weeks apart while on previous or current ARV therapy. Up to Week 96
Secondary Percentage of Participants With Adherence to Study Therapy An Adherence Questionnaire was to be given in order to determine the percentage of participants who adhered to study therapy. Up to Week 96
Secondary Change From Baseline in Bone Disease Risk Assessment Bone disease risk assessment was to be based on a Fracture Risk Assessment Tool (FRAX®) score in participants > 40 years old, and the change from baseline determined. Baseline and week 96
Secondary Change From Baseline in the VACS Index The Veterans Aging Cohort Risk Index (VACS Index) combines various clinical biomarkers into a cumulative index weighted according to the risk of all-cause mortality. Baseline and week 96
Secondary Percentage of Participants Experiencing a Decline of Renal Function Decline in renal function was to be assessed by evaluating MDRD-6, creatinine clearance and serum phosphate. Up to Week 96
Secondary Change From Baseline in eGFR at Week 96 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 96
See also
  Status Clinical Trial Phase
Completed NCT05454514 - Automated Medication Platform With Video Observation and Facial Recognition to Improve Adherence to Antiretroviral Therapy in Patients With HIV/AIDS N/A
Completed NCT03760458 - The Pharmacokinetics, Safety, and Tolerability of Abacavir/Dolutegravir/Lamivudine Dispersible and Immediate Release Tablets in HIV-1-Infected Children Less Than 12 Years of Age Phase 1/Phase 2
Recruiting NCT06033547 - A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Two Different Formulations of Long-acting Cabotegravir in Healthy Adult Participants Phase 1
Completed NCT03141918 - Effect of Supplementation of Bioactive Compounds on the Energy Metabolism of People Living With HIV / AIDS N/A
Completed NCT03067285 - A Phase IV, Open-label, Randomised, Pilot Clinical Trial Designed to Evaluate the Potential Neurotoxicity of Dolutegravir/Lamivudine/Abacavir in Neurosymptomatic HIV Patients and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide. DREAM Study Phase 4
Recruiting NCT04579146 - Coronary Artery Disease (CAD) in Patients HIV-infected
Completed NCT06212531 - Papuan Indigenous Model of Male Circumcision N/A
Active, not recruiting NCT03256422 - Antiretroviral Treatment Taken 4 Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients Phase 3
Completed NCT03256435 - Retention in PrEP Care for African American MSM in Mississippi N/A
Completed NCT00517803 - Micronutrient Supplemented Probiotic Yogurt for HIV/AIDS and Other Immunodeficiencies N/A
Active, not recruiting NCT03572335 - Systems Biology of Diffusion Impairment in Human Immunodeficiency Virus (HIV)
Completed NCT04165200 - Fecal Microbiota Transplantation as a Therapeutic Strategy for Patients Infected With HIV N/A
Recruiting NCT03854630 - Hepatitis B Virus Vaccination in HIV-positive Patients and Individuals at High Risk for HIV Infection Phase 4
Terminated NCT03275571 - HIV, Computerized Depression Therapy & Cognition N/A
Completed NCT02234882 - Study on Pharmacokinetics Phase 1
Completed NCT01618305 - Evaluating the Response to Two Antiretroviral Medication Regimens in HIV-Infected Pregnant Women, Who Begin Antiretroviral Therapy Between 20 and 36 Weeks of Pregnancy, for the Prevention of Mother-to-Child Transmission Phase 4
Recruiting NCT05043129 - Safety and Immune Response of COVID-19 Vaccination in Patients With HIV Infection
Not yet recruiting NCT06072443 - AURORA Study-A Transformative Approach to Support PrEP Medication Persistence
Not yet recruiting NCT05536466 - The Influence of Having Bariatric Surgery on the Pharmacokinetics, Safety and Efficacy of the Novel Non-nucleoside Reverse Transcriptase Inhibitor Doravirine N/A
Recruiting NCT04985760 - Evaluation of Trimer 4571 Therapeutic Vaccination in Adults Living With HIV on Suppressive Antiretroviral Therapy Phase 1