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

NCT01355354 | Completed Phase 1

• 1 other identifier: D4300C00026
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (2)

1

EXPERIMENTAL

Digoxin

Drug: Digoxin

2

EXPERIMENTAL

Fostamatinib

Drug: Digoxin; Drug: Fostamatinib

Interventions

Digoxin DRUG

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

1; 2

Fostamatinib DRUG

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

2

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 26514315 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Digoxin; fostamatinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2011
• First Posted: May 18, 2011
• Study Start: June 1, 2011
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: October 6, 2011

Record last verified: 2011-10

Locations

GB (1)