Clinical trial NCT01311622: Effects of Administration of Fostamatinib on Blood Concentrations of Warfarin in Healthy Subjects
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Healthy Subjects
Keywords: drug-drug interaction
Phase 1
healthy subjects
warfarin
Rheumatoid arthritis
RA
fostamatinib open-label
pharmacokinetics
pharmacodynamics
level of Warfarin in the blood
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-03-09
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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).

Primary outcomes:
measure: To determine PK parameters of R- and S-warfarin including but not limited to AUC and Cmax
timeFrame: From pre-dose to 168 h post dose relative to each single warfarin dose
Secondary outcomes:
measure: To measure International Normalised Ratio (INR) following administration of warfarin
timeFrame: From pre-dose to 168 h post dose relative to each single warfarin dose
measure: To assess the steady-state pharmacokinetics of R406 (active metabolite of fostamatinib) by measuring AUCss, Cmax,ss, tmax,ss and CL/F
timeFrame: From predose on Day 11 until 12 h post dose on Day 14 relative to fostamatinib dosing
measure: Safety and tolerability will be measured with regard to adverse events, laboratory assessments, vital signs, physical examination, and 12-lead ECG will be recorded.
timeFrame: From screening, Day -1 to Day 21 and follow up visit (Day 28)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Quintiles, Phase 1 Unit, London
name: James Ritter, BM BCh MRCP FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Mark Layton, MD MRCP (UK)
role: STUDY_DIRECTOR
References: