Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF)

January 21, 2021 updated by: University of Colorado, Denver

Effects of Ledipasvir/Sofosbuvir Treatment on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF) in Patients With HIV.

This study will evaluate the effect of ledipasvir/sofosbuvir (LDV/SOF) treatment on the pharmacokinetics (PK) and renal safety of tenofovir in the form of tenofovir alafenamide (TAF). Subjects living with human immunodeficiency virus (HIV) who are receiving tenofovir-based antiretroviral therapy (in the form of tenofovir disoproxil fumarate [TDF]), and are also taking a ritonavir- or cobicistat-boosted protease inhibitor will be invited to participate.

The study will consist of five visits: a screening visit, three abbreviated 4-hour pharmacokinetic visits, and one end-of-study follow-up visit.

Subjects will also be asked to use a Wisepill device, which will track medication adherence throughout the study.

Study Overview

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Between 18-70 years of age
  • Have been taking TDF and a ritonavir- or cobicistat-boosted protease inhibitor as part of standard care for treatment of HIV

Exclusion Criteria:

  • eGFR < 30 mL/min
  • Pregnant or planning pregnancy
  • Breastfeeding
  • Any medical, social, or mental-health issue(s) that, in the opinion of the investigators, could interfere with study participation or the study outcomes
  • Signs or symptoms of decompensated liver disease
  • Hepatitis B infection
  • Medications that may cause unwanted drug interactions with ledipasvir/sofosbuvir or emtricitabine/tenofovir alafenamide
  • Unwillingness or inability to comply with study procedures
  • Chronic hepatitis C infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: TAF with a boosted PI and LDV/SOF

Participants who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment.

Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide (TAF) 25 mg/emtricitabine (FTC) 200 mg (Descovy) with a boosted protease inhibitor for the next 12 weeks.

After taking TAF/FTC for 12 weeks, participants will then start taking ledipasvir 90mg/sofosbuvir 400mg (LDV/SOV, Harvoni) in combination with TAF/FTC and a boosted protease inhibitor for 4 weeks.

Participants will then return to taking TAF/FTC with a boosted protease inhibitor for the final 12 weeks of the study.

Participants who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment.

Other: Blood draws for tenofovir PK, renal function assessment

Other Names:
  • Viread or Truvada with a boosted protease inhibitor

Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide 25 mg/emtricitabine 200 mg with a boosted protease inhibitor.

Other: Blood draws for tenofovir PK, renal function assessment

Other Names:
  • Descovy with a boosted protease inhibitor

After taking tenofovir alafenamide/emtricitabine for 12 weeks, participants will then start taking ledipasvir 90 mg/sofosbuvir 400 mg (Harvoni) in combination with the tenofovir alafenamide 25 mg/emtricitabine 200 mg (Descovy) and a boosted protease inhibitor for 4 weeks. Subjects will then return to taking tenofovir alafenamide 25 mg/emtricitabine 200 mg (Descovy) and a boosted protease inhibitor for the final 12 weeks.

Other: Blood draws for tenofovir PK, renal function assessment

Other Names:
  • Descovy with a boosted protease inhibitor and Harvoni

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Week 12 Plasma Tenofovir Area Under the Plasma Concentration vs. Time Curve From Time 0 to 24 Hours (AUC0-24) at 24 and 28 Weeks
Time Frame: 12 weeks and 24 weeks and 28 weeks
Compare plasma tenofovir AUC0-24 between TAF with boosted PI vs. TDF with boosted PI (Phase 2 vs. 1), and between TAF with boosted PI and LDV/SOF vs. TDF with boosted PI (Phase 3 vs. 1)
12 weeks and 24 weeks and 28 weeks
Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cells (PBMCs) at 24 and 28 Weeks
Time Frame: 12 weeks, and 24 weeks and 28 weeks
Compare tenofovir-diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) between TAF with a boosted PI vs. TDF with a boosted PI (Phase 2 vs. 1), and TAF with a boosted PI and LDV/SOF vs. TDF with a boosted PI (Phase 3 vs. 1).
12 weeks, and 24 weeks and 28 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Dried Blood Spots (DBS)
Time Frame: 12 weeks and 24 and 28 weeks
Compare tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) between TAF with a boosted PI vs. TDF with a boosted PI (Phase 2 vs. 1), and TAF with a boosted PI and LDV/SOF vs. TDF with a boosted PI (Phase 3 vs. 1)
12 weeks and 24 and 28 weeks
Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: eGFR
Time Frame: 12 weeks, 24 weeks, and 28 weeks
Change in estimated glomerular filtration rate (eGFR)
12 weeks, 24 weeks, and 28 weeks
Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: UPCR
Time Frame: 12 weeks, 24 weeks, and 28 weeks
Change in estimated glomerular filtration rate (eGFR) and renal biomarkers: Urine protein to creatinine ratio (UPCR)
12 weeks, 24 weeks, and 28 weeks
Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: B2M/Cr Ratio, and RBP/Cr Ratio
Time Frame: 12 weeks, 24 weeks, and 28 weeks
Change in renal biomarkers: urinary beta-2 microglobulin (B2M)/creatinine (Cr) ratio, and urinary retinol binding protein (RBP)/Cr ratio
12 weeks, 24 weeks, and 28 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 8, 2018

Primary Completion (ACTUAL)

July 12, 2019

Study Completion (ACTUAL)

October 1, 2019

Study Registration Dates

First Submitted

April 19, 2017

First Submitted That Met QC Criteria

April 19, 2017

First Posted (ACTUAL)

April 24, 2017

Study Record Updates

Last Update Posted (ACTUAL)

February 11, 2021

Last Update Submitted That Met QC Criteria

January 21, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Not Applicable. As per the question above, we do not plan to share IPD

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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