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

Phase 1

Completed

• Conditions: Rheumatoid Arthritis; Healthy Subjects
• Interventions: Drug: warfarin; Drug: fostamatinib

• Registration Number: NCT01311622
• Lead Sponsor: AstraZeneca

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-02-21
• Study Start: 2011-03
• Study First Submitted QC: 2011-03-08
• Study First Posted: 2011-03-09
• Primary Completion: 2011-05
• Study Completion: 2011-05
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-30
• Last Update Posted: 2013-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
warfarin	warfarin	-
warfarin and fostamatinib	warfarin	-
warfarin and fostamatinib	fostamatinib	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	From predose on Day 11 until 12 h post dose on Day 14 relative to fostamatinib dosing	* 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
Safety and tolerability will be measured with regard to adverse events, laboratory assessments, vital signs, physical examination, and 12-lead ECG will be recorded.	From screening, Day -1 to Day 21 and follow up visit (Day 28)	To examine the safety and tolerability of fostamatinib in combination with Warfarin: Adverse events, laboratory assessments, vital signs, physical examination, and 12-lead ECG

Trial Locations

Locations (1)

Research Site; 🇬🇧 London, United Kingdom