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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency
• Intervention / Treatment: Drug: QAW039; Drug: QAW39A; Drug: QAW39A2107

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

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Grunstadt, Germany, 67269
    • Novartis Investigative Site
• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; ESRD patients	Drug: QAW039; 450 mg; Other Names: fevipiprant
Experimental: Group 2; healthy volunteers	Drug: QAW39A; 450 mg; Other Names: fevipiprant
Experimental: Group 3; severe and moderate renal impaired patients	Drug: QAW39A2107; 450 mg; Other Names: fevipiprant
Experimental: Group 4; mild renal impaired patients	Drug: QAW39A2107; 450 mg; Other Names: fevipiprant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Pharmacokinetics: Plasma concentration of fevipiprant by Cmax	Cmax is the observed maximum plasma concentration following drug administration	68 hours post dose
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
Pharmacokinetics of the metabolite CCN362 by Cmax	Cmax is the observed maximum plasma concentration following drug administration	68 hours post dose
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2017
• Primary Completion (Actual): August 7, 2018
• Study Completion (Actual): August 7, 2018

Study Registration Dates

• First Submitted: March 17, 2017
• First Submitted That Met QC Criteria: March 17, 2017
• First Posted (Actual): March 23, 2017

Study Record Updates

• Last Update Posted (Actual): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: renal impairment; end stage renal disase ESRD; dialysis effect on pharmacokinetics PK
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Physiological Effects of Drugs; Growth Substances; Plant Growth Regulators; Indoleacetic Acids
• Other Study ID Numbers: CQAW039A2107; 2016-004218-81 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No