Safety of Sofosbuvir in People With Advanced Kidney Failure
Status:
Completed
Trial end date:
2020-08-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 3
Details
Lead Sponsor:
Sanjay Gandhi Postgraduate Institute of Medical Sciences