A Phase 1 Study of Roxadustat in Subjects With Different Degrees of Renal Function
Condition: Normal Renal Function; Impaired Renal Function
MeSH terms: Renal Insufficiency
Study type: Interventional
Phase: Phase 1

Summary: 
      For subjects with normal renal function or severely impaired renal function, this study will
      evaluate the pharmacokinetics of roxadustat and its main metabolites in plasma and urine.

      For subjects with end stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis
      (CAPD) or automated peritoneal dialysis (APD), this study will evaluate the pharmacokinetics
      of roxadustat and its main metabolites in plasma, urine and dialysate.

      For subjects with ESRD on hemodialysis (HD) or hemodiafiltration (HDF), this study will
      evaluate the pharmacokinetics of roxadustat and its main metabolites in plasma, urine and
      dialysate and also the effect of dialysis on the pharmacokinetics of roxadustat and its main
      metabolites.
    

Detailed description: 
      This is a phase 1, open-label study in two sites. There will be four different renal function
      groups.

      For all subjects:

      Subjects will be allocated to the normal and severely impaired renal function groups based on
      estimated glomerular filtration rate (eGFR), calculated with the abbreviated modification of
      diet in renal disease (MDRD) equation. The eGFR will be based on the serum creatinine
      concentration and is assessed at screening and at day -2. The eGFR obtained at screening will
      determine the allocation.

      Subjects will be allocated to the ESRD groups based on their dialysis requirements.

      Subjects with normal and severely impaired renal function, and subjects with ESRD on CAPD or
      APD:

      Screening will take place from day -30 to day -3 and the subjects will be admitted to the
      clinical unit on day -2. The treatment period lasts 8 days, during which the subjects will
      receive a single oral dose of roxadustat in the morning of day 1 Subjects will complete the
      treatment period on day 6, provided that all required assessments have been performed and
      there are no medical reasons for a prolonged follow-up. The study will be completed with an
      end-of-study visit (ESV), which will take place between 5 and 9 days after the last treatment
      period-defined assessment (or after early withdrawal).

      Subjects with ESRD on HD or HDF:

      Screening will take place from day -30 to day -3 and subjects will complete 2 treatment
      periods of 8 days (period 1) and 7 days (period 2) in order to evaluate the pharmacokinetics
      of roxadustat with a single oral dose of roxadustat on day 1 of both periods after and before
      dialysis.

      Subjects will complete the treatment period 1 on day 6 followed by a wash-out period which is
      minimally 1 week and maximally 3 weeks. Subjects will complete period 2 on day 6, provided
      that all required assessments have been performed and there are no medical reasons for a
      prolonged follow-up. The study will be completed with an end-of-study visit (ESV), which will
      take place between 5 and 9 days after the last treatment period-defined assessment (or after
      early withdrawal).

      All subjects:

      Safety assessments will be performed throughout the study. An optional biobanking sample may
      be taken for potential exploratory, retrospective, gene polymorphism analysis. Roxadustat
      plasma, urine, and dialysate samples will be stored for potential exploratory metabolic
      profiling or exploratory biomarker analysis after the study.
    

Intervention name(s): Roxadustat
Intervention type(s): Drug
Intervention description(s): Oral
Other intervention name(s): FG-4592; ASP1517
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ASP1517; Normal renal function; Dialysis; Roxadustat; Metabolites; Pharmacokinetics; Impaired renal function