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Trial record 84 of 115 for:    "Viral Infectious Disease" | "Ledipasvir"

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

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ClinicalTrials.gov Identifier: NCT03126370
Recruitment Status : Recruiting
First Posted : April 24, 2017
Last Update Posted : June 13, 2019
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Hepatitis C HIV Coinfection Drug: TDF with a boosted protease inhibitor Drug: TAF with a boosted protease inhibitor Drug: TAF with a boosted protease inhibitor and LDV/SOF Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Effects of Ledipasvir/Sofosbuvir Treatment on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF) in Patients With HIV.
Actual Study Start Date : January 8, 2018
Estimated Primary Completion Date : August 31, 2019
Estimated Study Completion Date : August 31, 2019


Arm Intervention/treatment
Experimental: TAF with a boosted PI and LDV/SOF

Subjects 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.

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

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

Drug: TDF with a boosted protease inhibitor

Subjects 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 Name: Viread or Truvada with a boosted protease inhibitor

Drug: TAF with a boosted protease inhibitor

Subjects 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 Name: Descovy with a boosted protease inhibitor

Drug: TAF with a boosted protease inhibitor and LDV/SOF

After taking tenofovir alafenamide/emtricitabine for 12 weeks, subjects 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 Name: Descovy with a boosted protease inhibitor and Harvoni




Primary Outcome Measures :
  1. Change in area under the plasma concentration (AUC) of tenofovir [ Time Frame: Over the course of 40 weeks, will be assessed at 12 weeks, 24 weeks, 28 weeks, and 40 weeks. ]
    Compare tenofovir AUC0-24 before and after switching from TDF to TAF, and before and after administration of LDV/SOF

  2. Change in tenofovir diphosphate in peripheral blood mononuclear cells [ Time Frame: Over the course of 40 weeks, will be assessed at 12 weeks, 24 weeks, 28 weeks, and 40 weeks. ]
    Compare tenofovir diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMC's) when tenofovir is given as TDF and then switched to TAF and also when TAF is given with LDV/SOF


Secondary Outcome Measures :
  1. Change in tenofovir diphosphate in dried blood spots [ Time Frame: 24 and 28 weeks ]
    Compare tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) when tenofovir is given as TDF and then switched to TAF and also when TAF is given with LDV/SOF

  2. Change in Estimated Glomerular Filtration Rate (eGFR), urinary retinol binding protein/creatinine ratios, and urinary beta-2 microglobulin/creatinine ratios [ Time Frame: Over the course of 40 weeks, will be assessed at 12 weeks, 24 weeks, 28 weeks, and 40 weeks. ]
    Compare eGFR calculated using Modification of Diet in Renal Disease (MDRD) equation and other renal safety markers before and after the addition of LDV/SOF



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03126370


Contacts
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Contact: Jennifer J Kiser, PharmD 303-724-6131 jennifer.kiser@ucdenver.edu
Contact: Kristina M Brooks, PharmD 303-724-0395 kristina.brooks@ucdenver.edu

Locations
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United States, Colorado
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Jennifer J Kiser, PharmD    303-724-6131    jennifer.kiser@ucdenver.edu   
Contact: Kristina M Brooks, PharmD    303-724-0395    kristina.brooks@ucdenver.edu   
Sponsors and Collaborators
University of Colorado, Denver
Investigators
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Principal Investigator: Jennifer J Kiser, PharmD University of Colorado, Denver

Publications:
German P GK, Pang PS, et al. Drug Interactions Between the anti-HCV Regimen Ledipasvir/Sofosbuvir and Ritonavir-Boosted Protease Inhibitors plus Emtricitabine/Tenofovir DF. CROI 2015; February 23-26, 2015; Seattle WA.
MacBrayne CE MK, Fierer DS, et al. Increase Tenofovir Diphosphate in Red Blood Cells, but Not Tenofovir in Plasma, with Sofosbuvir and Ribavirin. 17th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy; Washington DC, June 2016 Accepted Abstract (Oral).
Garrison K ea. Drug Interactions between anti-HCV Antivirals Ledipasvir/Sofosbuvir and Integrase Strand Transfer Inhibitor-Based Regimens. 16th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, Washington DC. May 26-28, 2015, abstrac #71
Cope R PA, Glowa T, Faulds S, Veldkamp P, Prasad R. Majority of HIV/HCV Co-infected Patients Require Antiretroviral Therapy Switch Prior to Use of Simeprevir (abstract 651). CROI 2015; February 23-26, 2015. Seattle, WA.
Langness J LB, Rogers M, J. KJ. Readying HIV/HCV Coinfected Patients for HCV Treatment: Occurrence and Management of Antiviral Interactions (abstract 18). 16th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy; May 26-28, 2015; Washington, DC.
Castillo-Mancilla J, Coyle R, Zheng J, al e. Tenofovir Diphosphate Arising from TAF is Quantifiable in Dried Blood Spots. Conference on Retroviruses and Opportunistic Infections. Seattle Washington, February 13-16, 2017.

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03126370     History of Changes
Other Study ID Numbers: 17-0490
First Posted: April 24, 2017    Key Record Dates
Last Update Posted: June 13, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Not Applicable. As per the question above, we do not plan to share IPD

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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
Additional relevant MeSH terms:
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Virus Diseases
RNA Virus Infections
Ledipasvir
Ledipasvir, sofosbuvir drug combination
Coinfection
Hepatitis C
HIV Infections
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Flaviviridae Infections
Infection
Parasitic Diseases
Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Emtricitabine
Sofosbuvir
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
HIV Protease Inhibitors
Protease Inhibitors
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors