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

Study Overview
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Brief Summary
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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.

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

Conditions
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Rheumatoid Arthritis, Healthy Subjects

Intervention / Treatment
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* Drug: warfarin
* Drug: fostamatinib


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: warfarin<br> | Drug: warfarin<br>* 2 single 25 mg doses of Warfarin (5 x 5 mg tablets) administered 14 days apart<br>* Other names: Marevan;|
| Experimental: warfarin and fostamatinib<br> | Drug: warfarin<br>* 2 single 25 mg doses of Warfarin (5 x 5 mg tablets) administered 14 days apart<br>* Other names: Marevan;Drug: fostamatinib<br>* 2 x 50 mg Fostamatinib tablets (100 mg) twice daily for 13 days<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug-drug interaction, Phase 1, healthy subjects, warfarin, Rheumatoid arthritis, RA, fostamatinib open-label, pharmacokinetics, pharmacodynamics, level of Warfarin in the blood