Back to results

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

Primary Purpose

Rheumatoid Arthritis, Healthy Subjects

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

warfarin

fostamatinib

About this trial

This is an interventional basic science trial for Rheumatoid Arthritis focused on measuring drug-drug interaction, Phase 1, healthy subjects, warfarin, Rheumatoid arthritis, RA, fostamatinib open-label, pharmacokinetics, pharmacodynamics, level of Warfarin in the blood

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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).

Sites / Locations

Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

warfarin

warfarin and fostamatinib

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

Full Information

NCT ID

NCT01311622

First Posted

February 21, 2011

Last Updated

January 30, 2013

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT01311622

Brief Title

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

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Completed

Study Start Date

March 2011 (undefined)

Primary Completion Date

May 2011 (Actual)

Study Completion Date

May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

warfarin

Arm Type

Experimental

Arm Title

warfarin and fostamatinib

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

warfarin

Other Intervention Name(s)

Marevan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

fostamatinib

Intervention Description

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

Primary Outcome Measure Information:

Title

To determine PK parameters of R- and S-warfarin including but not limited to AUC and Cmax

Description

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 Outcome Measure Information:

Title

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

Title

To assess the steady-state pharmacokinetics of R406 (active metabolite of fostamatinib) by measuring AUCss, Cmax,ss, tmax,ss and CL/F

Description

Time Frame

From predose on Day 11 until 12 h post dose on Day 14 relative to fostamatinib dosing

Title

Safety and tolerability will be measured with regard to adverse events, laboratory assessments, vital signs, physical examination, and 12-lead ECG will be recorded.

Description

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

James Ritter, BM BCh MRCP FRCP

Organizational Affiliation

Quintiles, Phase 1 Unit, London

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Mark Layton, MD MRCP (UK)

Organizational Affiliation

AstraZeneca

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

London

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs