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

NCT ID: NCT02252731

Last Updated: 2014-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2013-11-30

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.

Detailed Description

The study consists of 2 periods, separated by a washout period (a minimum of 14 days after warfarin dosing on Day 1, Period 1). Screening takes place from Day -22 to Day -2.

Subjects are admitted to the clinical unit on Day -1 of Period 1. On Day 1 of the first period, subjects receive a single oral dose of warfarin. After completion of all assessments on Day 8, subjects are discharged from the clinical unit on the condition that there are no medical reasons for a prolonged stay. They return to the clinical unit on Day -1 of the second period, after the washout period.

In Period 2, the subjects receive multiple doses of FG 4592. On Day 7 of Period 2, FG 4592 is given concomitantly with warfarin. After completion of all assessments on Day 16 of Period 2, subjects are discharged from the clinic on the condition that there are no medical reasons for a prolonged stay. The subjects return for an End of Study Visit (ESV) 5 to 9 days after the last assessment of Period 2 (or after early withdrawal).

Safety assessments are performed throughout the study. Blood and urine samples are collected for PK and PD assessments.

Conditions

Pharmacokinetics of FG-4592; Healthy Subjects

Keywords

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

warfarin and FG-4592

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

Group Type: EXPERIMENTAL

Warfarin

Intervention Type: DRUG

Oral

FG-4592

Intervention Type: DRUG

Oral

Interventions

Warfarin

Oral

Intervention Type: DRUG

FG-4592

Oral

Intervention Type: DRUG

Other Intervention Names

Coumadin®; ASP1517,; roxadustat

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

FibroGen

INDUSTRY

Sponsor Role: collaborator

Astellas Pharma Europe B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Physician

Role: STUDY_DIRECTOR

Astellas Pharma Europe B.V.

Locations

Parexel International GmbH

Berlin, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 26947173 (View on PubMed)

Other Identifiers

2013-001043-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1517-CL-0509

Identifier Type: -

Identifier Source: org_study_id