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Completed

NCT Number: NCT03126370

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

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.

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Key information

Conditions

Hepatitis C Blood-Borne Infections Communicable Diseases Digestive System Diseases Flaviviridae Infections Genital Diseases HIV Coinfection HIV Infections Hepatitis Hepatitis, Viral, Human Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections Liver Diseases RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

TDF with a boosted protease inhibitor

Drug

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

TAF with a boosted protease inhibitor

Drug

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

TAF with a boosted protease inhibitor and LDV/SOF

Drug

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

Primary outcomes

  1. 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)

  2. 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).

Secondary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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

Sponsors and collaborators

Lead sponsor

University of Colorado, Denver

Other

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Apr 24, 2017
Registry last updated
Feb 11, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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