A Study to Evaluate the Effects of Multiple Doses of FG-4592 on the Exposure, Safety and Tolerability and Effect of Warfarin in Healthy Subjects

NCT02252731 | Completed Phase 1

• 2 other identifiers: 1517-CL-05092013-001043-31
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine the effect of multiple doses of FG-4592 on the pharmacokinetics (PK) of a single dose of warfarin. It will evaluate the safety and tolerability of warfarin alone and in combination with multiple doses of FG-4592, and will evaluate the effect of multiple doses of FG-4592 on the pharmacodynamics (PD) of warfarin.

Conditions

Pharmacokinetics of FG-4592; Healthy Subjects

Keywords

Phase I; FG-4592; Warfarin; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (2)

• PK of S-warfarin and R-warfarin in plasma measured by area under the curve from the time of dosing extrapolated to time infinity (AUCinf)

  Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)

• PK of S-warfarin and R-warfarin in plasma measured by maximum concentration (Cmax)

  Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)

Secondary Outcomes (5)

• PK profile of S-warfarin and R-warfarin in plasma

  Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)

• PK profile of FG-4592 in plasma

  Period 2 (Day 1 to Day 15)

• PK profile of FG-4592 in urine

  Period 2 (Day 7 to Day 8)

• Pharmacodynamics profile of warfarin in plasma

  Period 1 Day 1 to to ESV (5 to 9 days after the last protocol defined assessment of Period 2 (or after early withdrawal))

• Safety profile

  Screening (Day -22 to Day -2) to ESV (5 to 9 days after the last protocol defined assessment of Period 2 (or after early withdrawal))

Study Arms (1)

warfarin and FG-4592

EXPERIMENTAL

Single dose of warfarin and Multiple doses of FG-4592 in combination with a single dose of warfarin

Drug: Warfarin; Drug: FG-4592

Interventions

Warfarin DRUG

Oral

Also known as: Coumadin®

warfarin and FG-4592

FG-4592 DRUG

Oral

Also known as: ASP1517,, roxadustat

warfarin and FG-4592

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control.
• Male subject must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.
• Female subject must be either of non-childbearing potential or, if of childbearing potential, must have a negative pregnancy test at screening and Day -1 and must use two forms of birth control.
• Female subject must not donate ova starting at screening and throughout the study period and for 28 days after the final study drug administration.

You may not qualify if:

• Subject has a known or suspected hypersensitivity to FG 4592, warfarin, or any components of the formulations used.
• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to admission to the clinical unit \[Day -1\].
• Subject is lactose intolerant.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead
• Kyntra Bio: collaborator

Study Sites (1)

Parexel International GmbH

Berlin, 14050, Germany

Location

Related Publications (1)

• Groenendaal-van de Meent D, den Adel M, Rijnders S, Krebs-Brown A, Kerbusch V, Golor G, Schaddelee M. The Hypoxia-inducible Factor Prolyl-Hydroxylase Inhibitor Roxadustat (FG-4592) and Warfarin in Healthy Volunteers: A Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction Study. Clin Ther. 2016 Apr;38(4):918-28. doi: 10.1016/j.clinthera.2016.02.010. Epub 2016 Mar 4.

  PMID: 26947173 DERIVED

MeSH Terms

Interventions

Warfarin; roxadustat

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Study Physician

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2014
• First Posted: September 30, 2014
• Study Start: September 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: September 30, 2014

Record last verified: 2014-09

Locations

DE (1)