A Study of Fostamatinib in Subjects With Impaired Kidney Function

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT01245790

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis Renal Impairment	Drug: fostamatinib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

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 Start Date :

Nov 1, 2010

Actual Primary Completion Date :

Jun 1, 2011

Actual Study Completion Date :

Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Healthy subjects (Stage 1)	Drug: fostamatinib Oral tablets, single dose
Experimental: 2 Mild renal impairment (Stage 2)	Drug: fostamatinib Oral tablets, single dose
Experimental: 3 Moderate renal impairment (Stage 2)	Drug: fostamatinib Oral tablets, single dose
Experimental: 4 Severe renal impairment (Stage 2)	Drug: fostamatinib Oral tablets, single dose
Experimental: 5 End stage renal disease (Stage 1)	Drug: fostamatinib Oral tablets, single dose

Outcome Measures

Primary Outcome Measures

Plasma pharmacokinetic (PK) parameters []
Parameters include: AUC, Cmax

Secondary Outcome Measures

Safety and tolerability variables of fostamatinib 150mg: Adverse events, vital signs, physical examinations, clinical laboratory tests and electrocardiograms []
Urine PK parameters of R406 and its N-glucuronide metabolite []
PK parameters including but not limited to Amount excreted (Ae) and renal clearance (CLr)
The effects of differences in protein binding by assessment of unbound R406 PK []
PK parameters including, but not limited to, unbound AUC and unbound Cmaxt

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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