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

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT01311622

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

7.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis Healthy Subjects	Drug: warfarin Drug: fostamatinib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Mar 1, 2011

Actual Primary Completion Date :

May 1, 2011

Actual Study Completion Date :

May 1, 2011

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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).