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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03087942

Collaborator

(none)

Enrollment

Locations

Arms

13.1

Actual Duration (Months)

22.5

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Renal Insufficiency	Drug: QAW039 Drug: QAW39A Drug: QAW39A2107 Drug: QAW39A2107	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 5, 2017

Actual Primary Completion Date :

Aug 7, 2018

Actual Study Completion Date :

Aug 7, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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
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
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Orlando	Florida	United States	32809
2	Novartis Investigative Site	Grunstadt		Germany	67269

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT03087942

Other Study ID Numbers:

CQAW039A2107
2016-004218-81

First Posted:

Mar 23, 2017

Last Update Posted:

Dec 11, 2020

Last Verified:

Jun 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Novartis Pharmaceuticals

end stage renal disase ESRD

dialysis effect on pharmacokinetics PK

renal impairment

Additional relevant MeSH terms:

Renal Insufficiency

Indoleacetic Acids

Study Results

No Results Posted as of Dec 11, 2020