Renal Impairment, Rheumatoid Arthritis
Conditions
Keywords
Phase 1, healthy volunteers, volunteers with renal impairment, pharmacokinetics, Rheumatoid arthritis, RA, fostamatinib, Patients
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.
Interventions
DRUGfostamatinib
Oral tablets, single dose
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma pharmacokinetic (PK) parameters | — | Parameters include: AUC, Cmax |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed