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

AstraZeneca15 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Rheumatoid Arthritis Healthy Subjects

Interventions

warfarinDRUG

2 single 25 mg doses of Warfarin (5 x 5 mg tablets) administered 14 days apart

fostamatinibDRUG

2 x 50 mg Fostamatinib tablets (100 mg) twice daily for 13 days

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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).

Locations (1)

Research Site

London, United Kingdom

Outcomes

Primary Outcomes

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

Time frame: From pre-dose to 168 h post dose relative to each single warfarin dose

Secondary Outcomes

To measure International Normalised Ratio (INR) following administration of warfarin

Time frame: 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

Time frame: 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

Time frame: From screening, Day -1 to Day 21 and follow up visit (Day 28)

Data from ClinicalTrials.gov

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