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

Study Overview
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Brief Summary
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The purpose of this study is to investigate the drug interaction between fostamatinib and digoxin by comparing the safety, tolerability and plasma concentration of digoxin when administered alone and with fostamatinib in healthy subjects.

Official Title
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An Open-Label, Non-Randomised, 2-Period, Single Centre Study to Assess the Pharmacokinetics of Digoxin in Healthy Subjects When Administered Alone and in Combination With Fostamatinib 100 mg Twice Daily

Conditions
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Healthy Volunteers, Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Digoxin
* Drug: Fostamatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures Male or female subjects aged 18 to 45 years (inclusive) Minimum weight of 50 kg and body mass index (BMI) between 18 and 30 kg/m2 (inclusive) Female subjects must have a negative pregnancy test at screening and on Day -1,must not be lactating, and must be of non-childbearing potential Exclusion Criteria: History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs (except for cholecystectomy) Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of the investigational product Subjects who smoke more than 5 cigarettes or the equivalent in tobacco per day Absolute neutrophil count of <2500/mm3 or 2.5 x 109/L Previous treatment with fostamatinib or digoxin in the present study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Digoxin | Drug: Digoxin<br>* oral tablets, 0.25mg bd on Day 1 and 0.25 Once daily from Day 2 to 15<br>|
| Experimental: 2<br>Fostamatinib | Drug: Digoxin<br>* oral tablets, 0.25mg bd on Day 1 and 0.25 Once daily from Day 2 to 15<br>Drug: Fostamatinib<br>* oral tablets, 100mg (2 X 50mg) bd from Day 9 - 15<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate whether the plasma concentration-time profiles and resulting PK parameters of digoxin are altered during steady-state fostamatinib administration. Digoxin AUCss and Cmaxss will be measured |  | Day 8 and Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To examine the safety + tolerability of fostamatinib in combination with digoxin. Assessments: Adverse events, lab assessments, vital signs, phys exam,12-lead ECG. Absolute values and change in baseline for any of these parameters will be reported |  | From screening, Day 1 - Day 17, through to Follow up visit | 
| To examine the steady-state PK of R406 during co-administration of fostamatinib with digoxin at steady-state. R406 AUCss, tmaxss and Cmaxss will be measured |  | Day 15 | 
| To examine the urinary steady-state PK of digoxin in healthy subjects when administered alone and in combination with fostamatinib at steady-state. Digoxin Ae(0-t), Fe, and CLr will be measured |  | Day 8 and Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, healthy volunteers, pharmacokinetics, Rheumatoid arthritis, RA, Fostamatinib, Digoxin, drug-drug interaction, Scientific terminology: Rheumatoid arthritis, Fostamatinib, Digoxin, drug-drug interaction, Laymen terminology: Rheumatoid arthritis, Amount of Digoxin in blood