Clinical trial NCT01355354: Effects of Administration of Fostamatinib on Blood Concentrations of Digoxin in Healthy Subjects
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Rheumatoid Arthritis
Keywords: 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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-05-18
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Day 8 and Day 15
Secondary outcomes:
measure: 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
timeFrame: From screening, Day 1 - Day 17, through to Follow up visit
measure: 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
timeFrame: Day 15
measure: 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
timeFrame: Day 8 and Day 15
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
References:
citation: Martin P, Gillen M, Millson D, Oliver S, Brealey C, Elsby R, Baluom M, Lau D, Mant T. Effects of Fostamatinib on the Pharmacokinetics of Digoxin (a P-Glycoprotein Substrate): Results From in Vitro and Phase I Clinical Studies. Clin Ther. 2015 Dec 1;37(12):2811-22. doi: 10.1016/j.clinthera.2015.09.018. Epub 2015 Oct 26.