A Study of Fostamatinib in Subjects With Impaired Kidney Function

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Rheumatoid Arthritis, Renal Impairment

Intervention / Treatment
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* Drug: fostamatinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Healthy subjects (Stage 1) | Drug: fostamatinib<br>* Oral tablets, single dose<br>|
| Experimental: 2<br>Mild renal impairment (Stage 2) | Drug: fostamatinib<br>* Oral tablets, single dose<br>|
| Experimental: 3<br>Moderate renal impairment (Stage 2) | Drug: fostamatinib<br>* Oral tablets, single dose<br>|
| Experimental: 4<br>Severe renal impairment (Stage 2) | Drug: fostamatinib<br>* Oral tablets, single dose<br>|
| Experimental: 5<br>End stage renal disease (Stage 1) | Drug: fostamatinib<br>* Oral tablets, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetic (PK) parameters | Parameters include: AUC, Cmax |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RA, Phase 1, healthy volunteers, volunteers with renal impairment, pharmacokinetics, Rheumatoid arthritis, fostamatinib, Patients