Clinical trial NCT01245790: A Study of Fostamatinib in Subjects With Impaired Kidney Function
Official title: An Open-label, Phase I Study to Assess the Pharmacokinetics of R406 in Subjects With Renal Impairment Compared to Healthy Subjects Following Administration of a Single Dose of Fostamatinib 150 mg
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Renal Impairment
Keywords: Phase 1
healthy volunteers
volunteers with renal impairment
pharmacokinetics
Rheumatoid arthritis
RA
fostamatinib
Patients
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-11-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: A 2 stage study to evaluate the amount of fostamatinib in the blood and urine in subjects with impaired kidney (renal) function compared with healthy volunteers with normal renal function. Stage 1 will include healthy subjects and subjects with end stage renal disease, while Stage, 2 may include subjects with mild, moderate and/or severe renal impairment dependent on the outcome of Stage 1. The study will also evaluate safety and tolerability in subjects with renal impairment.


Eligibility criteria: Inclusion Criteria:

* Males or females (non child bearing potential) greater than or equal to 18 years of age with suitable veins for cannulation or repeated venipuncture and with a weight of at least 50 kg (110 lbs) and body mass index (BMI) between 18 and 40 kg/m2, inclusive
* Stable renal impairment with following creatinine clearance (CLCR): Stage 1 - End Stage Renal Disease (ESRD) \< 15 mL/min (requiring dialysis); Stage 2 - Mild renal impairment ≥ 50 to \< 80 mL/min; Moderate renal impairment ≥ 30 to \<50 mL/min; and severe renal impairment 15 to \< 30 mL/min
* Healthy subjects with normal renal function must have good health based on medical history, physical examination , echocardiogram and clinical laboratory evaluations including creatinine clearance \>80 ml/min"
* Negative screen for Human Immunodeficiency Virus and negative results for serum hepatitis B surface antigen and hepatitis C antibody

Exclusion Criteria:

* Subjects who have received any medications known to chronically alter drug absorption or elimination processes within 30 days of the first dose administration
* Absolute neutrophil count less than 1600/mm3 or 1.6 x 109 L.
* Healthy subjects only: Subjects who have received any prescribed systemic or topical medication within 14 days of the first dose administration
* Subjects with a history of multiple drug allergies or with a known allergy to the drug class of fostamatinib
* In the opinion of the Investigator, any evidence of additional severe or uncontrolled systemic disease (eg, currently unstable or uncompensated hepatic, cardiovascular, or respiratory disease) or laboratory finding

Primary outcomes:
measure: Plasma pharmacokinetic (PK) parameters
Secondary outcomes:
measure: Safety and tolerability variables of fostamatinib 150mg: Adverse events, vital signs, physical examinations, clinical laboratory tests and electrocardiograms
measure: Urine PK parameters of R406 and its N-glucuronide metabolite
measure: The effects of differences in protein binding by assessment of unbound R406 PK
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Research Site
state: Florida
Study officials:
affiliation: AstraZeneca
name: Mark Layton, MD
role: STUDY_DIRECTOR
affiliation: Orlando Clinical
name: Thomas Marbury, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Martin P, Oliver S, Gillen M, Marbury T, Millson D. Pharmacokinetic Properties of Fostamatinib in Patients With Renal or Hepatic Impairment: Results From 2 Phase I Clinical Studies. Clin Ther. 2015 Dec 1;37(12):2823-36. doi: 10.1016/j.clinthera.2015.09.016. Epub 2015 Oct 27.