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

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT01355354

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

6.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers Rheumatoid Arthritis	Drug: Digoxin Drug: Fostamatinib	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

21 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Jun 1, 2011

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: 1

Digoxin

Drug: Digoxin

oral tablets, 0.25mg bd on Day 1 and 0.25 Once daily from Day 2 to 15

Experimental: 2

Fostamatinib

Drug: Digoxin

oral tablets, 0.25mg bd on Day 1 and 0.25 Once daily from Day 2 to 15

Drug: Fostamatinib

oral tablets, 100mg (2 X 50mg) bd from Day 9 - 15

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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