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Safety of Sofosbuvir in People With Advanced Kidney Failure

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ClinicalTrials.gov Identifier: NCT03883698
Recruitment Status : Recruiting
First Posted : March 21, 2019
Last Update Posted : March 25, 2019
Sponsor:
Information provided by (Responsible Party):
Sanjay Gandhi Postgraduate Institute of Medical Sciences

Brief Summary:

Infection with hepatitis C virus (HCV), a hepatotropic RNA virus, is often chronic, and causes liver cirrhosis and liver cancer. The virus is transmitted through parenteral exposure. This infection is particularly common in those on maintenance hemodialysis.

Sofosbuvir, an inhibitor of HCV RNA-dependent RNA polymerase, forms the backbone of DAA-based anti-HCV treatment regimens. In pre-clinical pharmacokinetic studies, administration of the usual 400 mg daily dose to in presence of advanced kidney failure (estimated glomerular filtration rate [eGFR] of <30 ml/min) showed that serum levels of the sofosbuvir and GS-331007, the primary metabolite of sofosbuvir, were elevated by several folds. Hence, sofosbuvir is not approved for use in people on maintenance hemodialysis.

The newer DAAs (e.g. grazoprevir/elbasvir combination), which have been approved for use in people with eGFR <30 ml/min, are very costly and are not available in Asian countries including India. Hence, as a rescue measures, several physicians, including our group, have tried half-daily dose (i.e, 200 mg daily or 400mg on alternate days) of sofosbuvir and 60 mg daclatasvir in dialysis-dependent people, with good results in terms of both safety and efficacy. In fact, the use of this empirical 200 mg daily dose schedule has become common in clinical practice. However, this use is not based on any pharmacokinetic data.

Hence, it is proposed to study the pharmacokinetics of low-dose (200 mg daily or 400 mg alternate day) of sofosbuvir and GS-331007 metabolite in people with eGFR <30/min and active HCV infection.


Condition or disease Intervention/treatment Phase
Kidney Failure, Chronic Hepatitis C Drug: Sofosbuvir Drug: Daclatasvir 60 mg Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a three arm, case control study aimed at studying the pharmacokinetics of sofosbuvir and its major metabolite (GS-331007) in people with estimated GFR (eGFR) <30 ml/min. Two arms will include participants with advanced renal failure with eGFR below 30 ml/min and third arm will include participants with normal eGFR. Participants with eGFR <30 ml/min will receive sofosbuvir in doses of either 400mg on alternate days or 200mg daily. The participants with normal eGFR will receive the standard of care, i.e, 400mg of sofosbuvir daily
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pharmacokinetics of Low-dose Sofosbuvir in Dialysis-dependent Patients With Hepatitis C Virus Infection
Actual Study Start Date : March 15, 2019
Estimated Primary Completion Date : June 14, 2020
Estimated Study Completion Date : February 14, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Sofosbuvir

Arm Intervention/treatment
Experimental: ESRD, alternate day dose
Participants with end stage renal disease (eGFR <30 ml/min) and hepatitis C virus active infection and treated with sofosbuvir 400 mg on alternate days. Total duration of treatment will be 12 weeks
Drug: Sofosbuvir
Sofosbuvir is the backbone of the most of the currently used anti-HCV treatment regimens

Drug: Daclatasvir 60 mg
Daclatasvir, in combination with sofosbuvir, is approved for the treatment of hepatitis C virus infection in absence of liver cirrhosis

Experimental: ESRD, daily dose
Participants with end stage renal disease (eGFR <30 ml/min) and hepatitis C virus active infection and treated with sofosbuvir 200 mg daily doses. The total duration of treatment will be 12 weeks
Drug: Sofosbuvir
Sofosbuvir is the backbone of the most of the currently used anti-HCV treatment regimens

Drug: Daclatasvir 60 mg
Daclatasvir, in combination with sofosbuvir, is approved for the treatment of hepatitis C virus infection in absence of liver cirrhosis

Active Comparator: Control
Participants with normal eGFR and hepatitis C virus infection and treated with sofosbuvir 400 mg daily dose. The total duration of treatment will be 12 weeks
Drug: Sofosbuvir
Sofosbuvir is the backbone of the most of the currently used anti-HCV treatment regimens

Drug: Daclatasvir 60 mg
Daclatasvir, in combination with sofosbuvir, is approved for the treatment of hepatitis C virus infection in absence of liver cirrhosis




Primary Outcome Measures :
  1. Pharmacokinetics study [ Time Frame: At hour (from the time of drug administration) '0', 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24 on Day 1; hour 36 on Day 2; at hour 84 on Day 4; and at hour 156 on Day 7 ]
    To study the Maximum Plasma Concentration [Cmax] of sofosbuvir and its metabolite (GS-331007) in participants with eGFR below 30 ml/min who are treated with low-dose of sofosbuvir and compare it with that in people with normal eGFR.

  2. Pharmacokinetics study [ Time Frame: At hour (from the time of drug administration) '0', 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24 on Day 1; hour 36 on Day 2; at hour 84 on Day 4; and at hour 156 on Day 7 ]
    To study the Area Under the Curve [AUC] of sofosbuvir and its metabolite (GS-331007) in participants with eGFR below 30 ml/min who are treated with low-dose of sofosbuvir and compare it with that in people with normal eGFR.

  3. Pharmacokinetics study [ Time Frame: At hour (from the time of drug administration) '0', 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24 on Day 1; hour 36 on Day 2; at hour 84 on Day 4; and at hour 156 on Day 7 ]
    To study the Terminal Half Life [t1/2] of sofosbuvir and its metabolite (GS-331007) in participants with eGFR below 30 ml/min who are treated with low-dose of sofosbuvir and compare it with that in people with normal eGFR.


Secondary Outcome Measures :
  1. Clinical response [ Time Frame: 12 weeks after stopping anti-HCV treatment ]
    Proportion of participants with sustained virologic response at 12 weeks [SVR12] after discontinuation of anti-HCV treatment



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Ages Eligible for Study:   19 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants with:

    • hepatitis C virus infection with detectable HCV RNA in blood
    • naïve to direct acting antiviral drugs based anti-HCV treatment

Exclusion Criteria:

  • Hepatitis B virus co-infection
  • Human immunodeficiency virus co-infection
  • Clinical evidence of cirrhosis or portal hypertension such as ascites, esophageal or gastric varices on esophago-gastro-duodenoscopy, liver stiffness more than 15 KPa as measured with transient elastography or history of hepatic encephalopathy.

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): NCT03883698


Contacts
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Contact: Amit Goel, DM +91-522-249 ext 4400 agoel.ag@gmail.com
Contact: Rakesh Aggarwal, DM +919140312315 aggarwal.ra@gmail.com

Locations
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India
Sanjay Gandhi Postgraduate Institute of Medical Sciences Recruiting
Lucknow, Uttar Pradesh, India, 226014
Contact: Amit Goel, DM    5222494400    agoel.ag@gmail.com   
Sponsors and Collaborators
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Investigators
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Principal Investigator: Amit Goel, DM Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI)

Publications:
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Responsible Party: Sanjay Gandhi Postgraduate Institute of Medical Sciences
ClinicalTrials.gov Identifier: NCT03883698     History of Changes
Other Study ID Numbers: 2018-167-IMP-107
CTRI/2019/03/018011 ( Registry Identifier: Clinical Trials Registry - India )
First Posted: March 21, 2019    Key Record Dates
Last Update Posted: March 25, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: As of now, our group has not decided about sharing the IPD with other researchers in a publicly available platform. Though, if needed, we could try to share the needed information if our institute's ethic committee permits for the same.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Hepatitis
Hepatitis C
Hepatitis, Viral, Human
Renal Insufficiency
Kidney Failure, Chronic
Liver Diseases
Digestive System Diseases
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Sofosbuvir
Antiviral Agents
Anti-Infective Agents