Effects of Administration of Fostamatinib on Blood Concentrations of Warfarin in Healthy Subjects

An Open-Label, Single Centre Study to Assess the Pharmacokinetics and Pharmacodynamics of Warfarin When Co-Administered With Fostamatinib in Healthy Subjects

The purpose of this study is to determine whether fostamatinib influences the plasma concentration of warfarin and changes its blood thinning effect, and to investigate how safe and tolerable it is when administered with warfarin.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis; Healthy Subjects
• Intervention / Treatment: Drug: warfarin; Drug: fostamatinib

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures (including genotyping screening sample for CYP2C9 and VKORC1).
• Males or females (of non-childbearing potential) aged 18 to 55 years (inclusive)
• Subjects must be negative for occult blood (stool card) prior to administration.
• Body weight of at least 50 kg and body mass index (BMI) between 18 and 35 kg/m2 inclusive

Exclusion Criteria:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, or influence the results of the study.
• Healthy subject predicted to be most sensitive to warfarin based on CYP2C9 and VKORC1 genotypes.
• A protein C and/or protein S deficiency.
• Absolute neutrophil count of less than 2500/mm3 or 2.5 x 109/L
• Previous treatment with warfarin for a clinical indication (ie, participation in a previous warfarin interaction study is acceptable).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: warfarin	Drug: warfarin; 2 single 25 mg doses of Warfarin (5 x 5 mg tablets) administered 14 days apart; Other Names: Marevan
EXPERIMENTAL: warfarin and fostamatinib	Drug: warfarin; 2 single 25 mg doses of Warfarin (5 x 5 mg tablets) administered 14 days apart; Other Names: Marevan; Drug: fostamatinib; 2 x 50 mg Fostamatinib tablets (100 mg) twice daily for 13 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine PK parameters of R- and S-warfarin including but not limited to AUC and Cmax	Pharmacokinetics of warfarin measured by AUC; Pharmacokinetics of warfarin measured Cmax	From pre-dose to 168 h post dose relative to each single warfarin dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure International Normalised Ratio (INR) following administration of warfarin		From pre-dose to 168 h post dose relative to each single warfarin dose
To assess the steady-state pharmacokinetics of R406 (active metabolite of fostamatinib) by measuring AUCss, Cmax,ss, tmax,ss and CL/F	Steady state Pharmacokinetics of R406 measured by AUCss; Steady state Pharmacokinetics of R406 measured by Cmax; Steady state Pharmacokinetics of R406 measured by ss; Steady state Pharmacokinetics of R406 measured by tmax; Steady state Pharmacokinetics of R406 measured by CL/F	From predose on Day 11 until 12 h post dose on Day 14 relative to fostamatinib dosing
Safety and tolerability will be measured with regard to adverse events, laboratory assessments, vital signs, physical examination, and 12-lead ECG will be recorded.	To examine the safety and tolerability of fostamatinib in combination with Warfarin: Adverse events, laboratory assessments, vital signs, physical examination, and 12-lead ECG	From screening, Day -1 to Day 21 and follow up visit (Day 28)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: James Ritter, BM BCh MRCP FRCP, Quintiles, Phase 1 Unit, London; Study Director: Mark Layton, MD MRCP (UK), AstraZeneca

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (ACTUAL): May 1, 2011
• Study Completion (ACTUAL): May 1, 2011

Study Registration Dates

• First Submitted: February 21, 2011
• First Submitted That Met QC Criteria: March 8, 2011
• First Posted (ESTIMATE): March 9, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): January 31, 2013
• Last Update Submitted That Met QC Criteria: January 30, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: pharmacokinetics; Phase 1; healthy subjects; warfarin; pharmacodynamics; Rheumatoid arthritis; drug-drug interaction; RA; fostamatinib open-label; level of Warfarin in the blood
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Anticoagulants; Warfarin
• Other Study ID Numbers: D4300C00013