Pharmacokinetics and Safety of Fevipiprant in Patients With Renal Impairment Compared to Matched Healthy Subjects
- Conditions
- Renal Insufficiency
- Interventions
- Drug: QAW039Drug: QAW39ADrug: QAW39A2107
- Registration Number
- NCT03087942
- Lead Sponsor
- Novartis Pharmaceuticals
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1 QAW039 ESRD patients Group 2 QAW39A healthy volunteers Group 3 QAW39A2107 severe and moderate renal impaired patients Group 4 QAW39A2107 mild renal impaired patients
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
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: 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
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
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
Trial Locations
- Locations (1)
Novartis Investigative Site
🇩🇪Grunstadt, Germany