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

Primary Purpose

Renal Insufficiency

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

QAW039

QAW39A

QAW39A2107

About this trial

This is an interventional treatment trial for Renal Insufficiency focused on measuring end stage renal disase ESRD, dialysis effect on pharmacokinetics PK, renal impairment

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Group 1

Group 2

Group 3

Group 4

Arm Description

ESRD patients

healthy volunteers

severe and moderate renal impaired patients

mild renal impaired patients

Outcomes

Primary Outcome Measures

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

Pharmacokinetics: Plasma concentration of fevipiprant by AUCinf

AUCinf is the area under the plasma concentration-time curve from time zero to infinity

Pharmacokinetics: Plasma concentration of fevipiprant by Cmax

Cmax is the observed maximum plasma concentration following drug administration

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

Secondary Outcome Measures

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

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

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

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

Pharmacokinetics of the metabolite CCN362 by AUCinf

AUCinf is the area under the plasma concentration time curve from time zero to infinity

Pharmacokinetics of the metabolite CCN362 by Cmax

Cmax is the observed maximum plasma concentration following drug administration

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

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

Full Information

NCT ID

NCT03087942

First Posted

March 17, 2017

Last Updated

December 9, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03087942

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Completed

Study Start Date

July 5, 2017 (Actual)

Primary Completion Date

August 7, 2018 (Actual)

Study Completion Date

August 7, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Insufficiency

Keywords

end stage renal disase ESRD, dialysis effect on pharmacokinetics PK, renal impairment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Experimental

Arm Description

ESRD patients

Arm Title

Group 2

Arm Type

Experimental

Arm Description

healthy volunteers

Arm Title

Group 3

Arm Type

Experimental

Arm Description

severe and moderate renal impaired patients

Arm Title

Group 4

Arm Type

Experimental

Arm Description

mild renal impaired patients

Intervention Type

Drug

Intervention Name(s)

QAW039

Other Intervention Name(s)

fevipiprant

Intervention Description

450 mg

Intervention Type

Drug

Intervention Name(s)

QAW39A

Other Intervention Name(s)

fevipiprant

Intervention Description

450 mg

Intervention Type

Drug

Intervention Name(s)

QAW39A2107

Other Intervention Name(s)

fevipiprant

Intervention Description

450 mg

Intervention Type

Drug

Intervention Name(s)

QAW39A2107

Other Intervention Name(s)

fevipiprant

Intervention Description

450 mg

Primary Outcome Measure Information:

Title

Pharmacokinetics: Plasma concentration of fevipiprant by AUClast

Description

AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration

Time Frame

68 hours post dose

Title

Pharmacokinetics: Plasma concentration of fevipiprant by AUCinf

Description

AUCinf is the area under the plasma concentration-time curve from time zero to infinity

Time Frame

68 hours post dose

Title

Pharmacokinetics: Plasma concentration of fevipiprant by Cmax

Description

Cmax is the observed maximum plasma concentration following drug administration

Time Frame

68 hours post dose

Title

Pharmacokinetics: Plasma contentration of fevipiprant by AUC0-68h

Description

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

Time Frame

68 hours post dose

Secondary Outcome Measure Information:

Title

Relationship between plasma pharmacokinetics of fevipiprant by AUClast and between eGFR as well as creatinine clearance

Description

Time Frame

68 hours post dose

Title

Relationship between plasma pharmacokinetics of fevipiprant by AUCinf and between eGFR as well as creatinine clearance

Description

Time Frame

68 hours post dose

Title

Relationship between plasma pharmacokinetics of fevipiprant by Cmax and between eGFR as well as creatinine clearance

Description

Time Frame

68 hours post dose

Title

Pharmacokinetics of the metabolite CCN362 by AUClast

Description

AUClast is the area under the plasma concentration time curve from time zero to the time of the last quantifiable concentration

Time Frame

68 hours post dose

Title

Pharmacokinetics of the metabolite CCN362 by AUCinf

Description

AUCinf is the area under the plasma concentration time curve from time zero to infinity

Time Frame

68 hours post dose

Title

Pharmacokinetics of the metabolite CCN362 by Cmax

Description

Cmax is the observed maximum plasma concentration following drug administration

Time Frame

68 hours post dose

Title

Pharmacokinetics: plasma concentration of fevipiprant in patients with End Stage Renal Disease (ESRD)

Description

Partial AUCs (AUCt1-t2) covering the time interval of dialysis, Cmax and total AUCs (AUC0-68h and/or AUCinf) will be compared

Time Frame

68 hours post dose

Title

urinary excretion of fevipiprant and metabolite in patients with renal impairment compared to healthy controls

Description

Renal clearance (CLr) and fraction of dose excreted in urine for fevipiprant and metabolite

Time Frame

24 hours post dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Orlando

State/Province

Florida

ZIP/Postal Code

32809

Country

United States

Facility Name

Novartis Investigative Site

City

Grunstadt

ZIP/Postal Code

67269

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17506

Description

Results for CQAW039A2107 can be found on the Novartis Clinical Trial Results Website

URL

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=289

Description

A Plain Language Trial Summary is available on novartisclinicatrials.com

Learn more about this trial

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

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