Pharmacokinetics and Safety of Fevipiprant in Patients With Renal Impairment Compared to Matched Healthy Subjects

Renal Insufficiency Clinical Trial

Official title:

An Open-label, Single-dose, Parallel Group Study to Assess the Pharmacokinetics of Fevipiprant (QAW039) in Patients With End-stage Renal Disease on Hemodialysis and Optionally in Patients With Severe to Moderate and Mild Renal Impairment Compared to Matched Healthy Volunteers Including a Cross-over Assessment in End-stage Renal Disease Patients on the Effect of Dialysis on Fevipiprant Pharmacokinetics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03087942
• Other study ID #: CQAW039A2107
• Secondary ID: 2016-004218-81
• Status: Completed
• Phase: Phase 1
• Start date: July 5, 2017
• Est. completion date: August 7, 2018

Study information

• Verified date: June 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: August 7, 2018
• Est. primary completion date: August 7, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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, ?-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)

Related Conditions & MeSH terms

• Renal Insufficiency

Intervention

Drug:
• QAW039
450 mg
• QAW39A
450 mg
• QAW39A2107
450 mg
• QAW39A2107
450 mg

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Grunstadt
United States	Novartis Investigative Site	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics: Plasma concentration of fevipiprant by AUClast	AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration	68 hours post dose
Primary	Pharmacokinetics: Plasma concentration of fevipiprant by AUCinf	AUCinf is the area under the plasma concentration-time curve from time zero to infinity	68 hours post dose
Primary	Pharmacokinetics: Plasma concentration of fevipiprant by Cmax	Cmax is the observed maximum plasma concentration following drug administration	68 hours post dose
Primary	Pharmacokinetics: Plasma contentration of fevipiprant by AUC0-68h	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	68 hours post dose
Secondary	Relationship between plasma pharmacokinetics of fevipiprant by AUClast and between eGFR as well as creatinine clearance	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	68 hours post dose
Secondary	Relationship between plasma pharmacokinetics of fevipiprant by AUCinf and between eGFR as well as creatinine clearance	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	68 hours post dose
Secondary	Relationship between plasma pharmacokinetics of fevipiprant by Cmax and between eGFR as well as creatinine clearance	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	68 hours post dose
Secondary	Pharmacokinetics of the metabolite CCN362 by AUClast	AUClast is the area under the plasma concentration time curve from time zero to the time of the last quantifiable concentration	68 hours post dose
Secondary	Pharmacokinetics of the metabolite CCN362 by AUCinf	AUCinf is the area under the plasma concentration time curve from time zero to infinity	68 hours post dose
Secondary	Pharmacokinetics of the metabolite CCN362 by Cmax	Cmax is the observed maximum plasma concentration following drug administration	68 hours post dose
Secondary	Pharmacokinetics: plasma concentration of fevipiprant in patients with End Stage Renal Disease (ESRD)	Partial AUCs (AUCt1-t2) covering the time interval of dialysis, Cmax and total AUCs (AUC0-68h and/or AUCinf) will be compared	68 hours post dose
Secondary	urinary excretion of fevipiprant and metabolite in patients with renal impairment compared to healthy controls	Renal clearance (CLr) and fraction of dose excreted in urine for fevipiprant and metabolite	24 hours post dose

External Links

•   A Plain Language Trial Summary is available on novartisclinicatrials.com
•   Results for CQAW039A2107 can be found on the Novartis Clinical Trial Results Website