Renal Insufficiency
Conditions
Keywords
end stage renal disase ESRD, dialysis effect on pharmacokinetics PK, renal impairment
Brief summary
The aim of the study is to assess whether renal impairment could affect fevipiprant pharmacokinetics (PK) to the extent that dosage adjustment is appropriate for this patient population. The study also aims to determine the effect of dialysis on the fevipiprant pharmacokinetic profile as the procedure might remove a significant fraction of the drug.
Detailed description
The purpose of this study is to determine if the pharmacokinetic profile of fevipiprant is different in patients with renal impariment compared to healthy matched volunteers to an extent that would require an adjustment of the dosage. Data from this study will be used to guide enrollment criteria in future clinical trials and to support regulatory submission and labeling information
Interventions
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy subjects must satisfy the criteria for normal renal function as evidenced by normal Glomerular Filtration Rate (GFR): eGFR ≥ 90 mL/min/1.73m2; each healthy subject must match in age (+/- 10years), gender, smoking status, and weight (+/- 15%), a patient from the renail impaired patient groups: * A body mass index (BMI) within the range of 18 - 36 kg/m2 * ESRD patients on hemodialysis: an glomerulo filtration rat GFR of \< 15 mL/min/1.73 m2 * patients with severe renal impairment: GFR of\< 30 mL/min/1.73m2 (without need of hemodialysis); * patients with moderate renal impairment: 30 mL/min/1.73m2 ≤ eGFR \< 60 mL/min/1.73m2; * patients with mild impairment: 60 mL/min/1.73m2 ≤ eGFR \< 90 mL/min/1.73m2
Exclusion criteria
* Pregnant or nursing (lactating) women * History or evidence of any inherited bilirubin disease or disorder * subjects participating in another study * malignancies in the past * Hemoglobin levels below 10 g/dL at screening * HIV positiv * Heavy smokers (≥20 cigarettes per day) * Liver disease, as indicated by ALT, γ-GT, AST and alkaline phosphatase which should not exceed twice the upper limit of normal and should be stable (e.g. increased liver values known from previous patient records). Serum bilirubin \> 27 μmol/L (1.6 mg/dL) * Clinically significant ECG changes and/or arrhythmias * Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Plasma concentration of fevipiprant by AUClast | 68 hours post dose | AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration |
| Pharmacokinetics: Plasma concentration of fevipiprant by AUCinf | 68 hours post dose | AUCinf is the area under the plasma concentration-time curve from time zero to infinity |
| Pharmacokinetics: Plasma concentration of fevipiprant by Cmax | 68 hours post dose | Cmax is the observed maximum plasma concentration following drug administration |
| Pharmacokinetics: Plasma contentration of fevipiprant by AUC0-68h | 68 hours post dose | AUC0-68h is the area under the plasma concentration from time zero to time 68 hours of the last measured concentration above the limit of quantification after dosing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of the metabolite CCN362 by AUCinf | 68 hours post dose | AUCinf is the area under the plasma concentration time curve from time zero to infinity |
| Pharmacokinetics of the metabolite CCN362 by Cmax | 68 hours post dose | Cmax is the observed maximum plasma concentration following drug administration |
| Pharmacokinetics of the metabolite CCN362 by AUClast | 68 hours post dose | AUClast is the area under the plasma concentration time curve from time zero to the time of the last quantifiable concentration |
| urinary excretion of fevipiprant and metabolite in patients with renal impairment compared to healthy controls | 24 hours post dose | Renal clearance (CLr) and fraction of dose excreted in urine for fevipiprant and metabolite |
| Pharmacokinetics: plasma concentration of fevipiprant in patients with End Stage Renal Disease (ESRD) | 68 hours post dose | Partial AUCs (AUCt1-t2) covering the time interval of dialysis, Cmax and total AUCs (AUC0-68h and/or AUCinf) will be compared |
| Relationship between plasma pharmacokinetics of fevipiprant by AUClast and between eGFR as well as creatinine clearance | 68 hours post dose | AUClast (the area under the plasma concentration time curve from time zero to the time of the last quantifiable concentration ) related to eGFR estimated by the Modification of Diet in Renal Disease (MDRD) formula, and Cockcroft-Gault (C-G) estimated creatinine clearance |
| Relationship between plasma pharmacokinetics of fevipiprant by AUCinf and between eGFR as well as creatinine clearance | 68 hours post dose | AUCinf (the area under the plasma concentration time curve from time zero to infinity) related to eGFR estimated by the Modification of Diet in Renal Disease (MDRD) formula, and Cockcroft-Gault (C-G) estimated creatinine clearance |
| Relationship between plasma pharmacokinetics of fevipiprant by Cmax and between eGFR as well as creatinine clearance | 68 hours post dose | Cmax (observed maximum plasma concentration following drug administration) related to eGFR estimated by the Modification of Diet in Renal Disease (MDRD) formula, and Cockcroft-Gault (C-G) estimated creatinine clearance |
Countries
Germany, United States
Outcome results
None listed