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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01311622
First received: February 21, 2011
Last updated: January 30, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Rheumatoid Arthritis
Healthy Subjects
Drug: warfarin
Drug: fostamatinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • To determine PK parameters of R- and S-warfarin including but not limited to AUC and Cmax [ Time Frame: From pre-dose to 168 h post dose relative to each single warfarin dose ] [ Designated as safety issue: No ]
    • Pharmacokinetics of warfarin measured by AUC
    • Pharmacokinetics of warfarin measured Cmax


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • To assess the steady-state pharmacokinetics of R406 (active metabolite of fostamatinib) by measuring AUCss, Cmax,ss, tmax,ss and CL/F [ Time Frame: From predose on Day 11 until 12 h post dose on Day 14 relative to fostamatinib dosing ] [ Designated as safety issue: No ]
    • 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. [ Time Frame: From screening, Day -1 to Day 21 and follow up visit (Day 28) ] [ Designated as safety issue: Yes ]
    To examine the safety and tolerability of fostamatinib in combination with Warfarin: Adverse events, laboratory assessments, vital signs, physical examination, and 12-lead ECG


Enrollment: 15
Study Start Date: March 2011
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: warfarin Drug: warfarin
2 single 25 mg doses of Warfarin (5 x 5 mg tablets) administered 14 days apart
Other Name: Marevan
Experimental: warfarin and fostamatinib Drug: warfarin
2 single 25 mg doses of Warfarin (5 x 5 mg tablets) administered 14 days apart
Other Name: Marevan
Drug: fostamatinib
2 x 50 mg Fostamatinib tablets (100 mg) twice daily for 13 days

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01311622

Locations
United Kingdom
Research Site
London, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: James Ritter, BM BCh MRCP FRCP Quintiles, Phase 1 Unit, London
Study Director: Mark Layton, MD MRCP (UK) AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01311622     History of Changes
Other Study ID Numbers: D4300C00013
Study First Received: February 21, 2011
Last Updated: January 30, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by AstraZeneca:
drug-drug interaction
Phase 1
healthy subjects
warfarin
Rheumatoid arthritis
RA
fostamatinib open-label
pharmacokinetics
pharmacodynamics
level of Warfarin in the blood

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014