Healthy Subjects, Rheumatoid Arthritis
Conditions
Keywords
drug-drug interaction, Phase 1, healthy subjects, warfarin, Rheumatoid arthritis, RA, fostamatinib open-label, pharmacokinetics, pharmacodynamics, level of Warfarin in the blood
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.
Interventions
DRUGwarfarin
2 single 25 mg doses of Warfarin (5 x 5 mg tablets) administered 14 days apart
DRUGfostamatinib
2 x 50 mg Fostamatinib tablets (100 mg) twice daily for 13 days
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United Kingdom
Outcome results
None listed