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Pharmacokinetics of Fevipiprant (QAW039) in Patients With Hepatic Impairment Compared to Matched Healthy Subjects

Primary Purpose

Hepatic Impairment

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Fevipiprant

About this trial

This is an interventional other trial for Hepatic Impairment focused on measuring Hepatic impairment,, Fevipiprant,, adults,, pharmacokinetics

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

All subjects

- Weight of at least 50 kg and no more than 120 kg and have a body mass index in the range 18.0-36.0 kg/m2

Patients with hepatic impairment

Moderate hepatic impairment (Group 1): Child-Pugh Class B (7-9 points),
Severe hepatic impairment (Group 2): Child-Pugh Class C (10-15 points
Mild hepatic impairment (Group 4): Child-Pugh Class A (5-6 points)

Healthy subjects

Match in age (±5 years), gender, smoking status, and weight (± 15%) to an individual patient.
In good health as determined by past medical history, physical examination, electrocardiogram, laboratory tests and urinalysis at screening.

Exclusion Criteria:

All subjects

History of hypersensitivity and/or idiosyncracies to QAW039 or to drugs of similar classes (CRTh2 antagonists).
Use of co-medications that may impact QAW039 exposure such as broad range UGT inhibitors or strong inhibitors of OAT3, OATP1B3, and P-gp, including but not limited to probenecid, ritonavir, valproic acid, and rifampin
Surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
Pregnant or nursing (lactating) women.
Women of child-bearing potential

Patients with hepatic impairment

Hepatic impairment due to non-liver disease (e.g., right heart failure)
Current symptoms or history of encephalopathy Grade III or IV within the past 6 months
Primary biliary liver cirrhosis and biliary obstruction
Emergency room visit or hospitalization due to liver disease within the preceding 3 months.
Severe complications of liver disease within the preceding 3 months.

Healthy subjects

Liver disease or liver injury as indicated by abnormal liver function tests.
Any single parameter of ALT, AST, γ-GT, alkaline phosphatase or serum bilirubin must not exceed 1.5 x upper limit of normal (ULN)
Any elevation above ULN of more than one parameter of ALT, AST, γ GT, alkaline phosphatase or serum bilirubin will exclude a subject from participation in the study
A positive Hepatitis B surface antigen or Hepatitis C test result.

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fevipiprant 450mg

Arm Description

450mg Film Coated Tablet

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

Secondary Outcome Measures

Relationship between plasma pharmacokinetics of Fevipiprant by AUClast and baseline hepatic function.

AUClast (the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration ) related to Child Pugh score

Relationship between plasma pharmacokinetics of Fevipiprant by AUCinf and baseline hepatic function.

AUCinf (the area under the plasma concentration-time curve from time zero to infinity) related to Child Pugh score

Relationship between plasma pharmacokinetics of Fevipiprant by Cmax and baseline hepatic function.

Cmax is the observed maximum plasma concentration following drug administration related to Child Pugh score

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

Full Information

NCT ID

NCT03048448

First Posted

January 27, 2017

Last Updated

December 9, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03048448

Brief Title

Pharmacokinetics of Fevipiprant (QAW039) in Patients With Hepatic 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 Hepatic Impairment Compared to Matched Healthy Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Completed

Study Start Date

May 31, 2017 (Actual)

Primary Completion Date

April 22, 2019 (Actual)

Study Completion Date

April 22, 2019 (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

This study will characterize the pharmacokinetics (PK) of QAW039 after a single oral dose of QAW039 in patients with hepatic impairment compared to healthy matched control subjects.

Detailed Description

The purpose of this study is to determine if the pharmacokinetic profile of Fevipiprant is different in patients with hepatic impairment 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

Hepatic Impairment

Keywords

Hepatic impairment,, Fevipiprant,, adults,, pharmacokinetics

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fevipiprant 450mg

Arm Type

Experimental

Arm Description

450mg Film Coated Tablet

Intervention Type

Drug

Intervention Name(s)

Fevipiprant

Other Intervention Name(s)

QAW039

Intervention Description

Single 450mg dose

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

120 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

120 hours post-dose

Title

Pharmacokinetics: Plasma concentration of Fevipiprant by Cmax

Description

Cmax is the observed maximum plasma concentration following drug administration

Time Frame

120 hours post-dose

Secondary Outcome Measure Information:

Title

Relationship between plasma pharmacokinetics of Fevipiprant by AUClast and baseline hepatic function.

Description

AUClast (the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration ) related to Child Pugh score

Time Frame

120 hours post-dose

Title

Relationship between plasma pharmacokinetics of Fevipiprant by AUCinf and baseline hepatic function.

Description

AUCinf (the area under the plasma concentration-time curve from time zero to infinity) related to Child Pugh score

Time Frame

120 hours post-dose

Title

Relationship between plasma pharmacokinetics of Fevipiprant by Cmax and baseline hepatic function.

Description

Cmax is the observed maximum plasma concentration following drug administration related to Child Pugh score

Time Frame

120 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

120 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

120 hours post-dose

Title

Pharmacokinetics of the metabolite CCN362 by Cmax

Description

Cmax is the observed maximum plasma concentration following drug administration

Time Frame

120 hours post-dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: All subjects - Weight of at least 50 kg and no more than 120 kg and have a body mass index in the range 18.0-36.0 kg/m2 Patients with hepatic impairment Moderate hepatic impairment (Group 1): Child-Pugh Class B (7-9 points), Severe hepatic impairment (Group 2): Child-Pugh Class C (10-15 points Mild hepatic impairment (Group 4): Child-Pugh Class A (5-6 points) Healthy subjects Match in age (±5 years), gender, smoking status, and weight (± 15%) to an individual patient. In good health as determined by past medical history, physical examination, electrocardiogram, laboratory tests and urinalysis at screening. Exclusion Criteria: All subjects History of hypersensitivity and/or idiosyncracies to QAW039 or to drugs of similar classes (CRTh2 antagonists). Use of co-medications that may impact QAW039 exposure such as broad range UGT inhibitors or strong inhibitors of OAT3, OATP1B3, and P-gp, including but not limited to probenecid, ritonavir, valproic acid, and rifampin Surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. Pregnant or nursing (lactating) women. Women of child-bearing potential Patients with hepatic impairment Hepatic impairment due to non-liver disease (e.g., right heart failure) Current symptoms or history of encephalopathy Grade III or IV within the past 6 months Primary biliary liver cirrhosis and biliary obstruction Emergency room visit or hospitalization due to liver disease within the preceding 3 months. Severe complications of liver disease within the preceding 3 months. Healthy subjects Liver disease or liver injury as indicated by abnormal liver function tests. Any single parameter of ALT, AST, γ-GT, alkaline phosphatase or serum bilirubin must not exceed 1.5 x upper limit of normal (ULN) Any elevation above ULN of more than one parameter of ALT, AST, γ GT, alkaline phosphatase or serum bilirubin will exclude a subject from participation in the study A positive Hepatitis B surface antigen or Hepatitis C test result.

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

Anaheim

State/Province

California

ZIP/Postal Code

92801

Country

United States

Facility Name

Novartis Investigative Site

City

Orlando

State/Province

Florida

ZIP/Postal Code

32809

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17633

Description

Results for CQAW039A2108 from the Novartis Clinical Trials Website

URL

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=516

Description

A Plain Language Trial Summary is available on novartisclinicatrials.com

Learn more about this trial

Pharmacokinetics of Fevipiprant (QAW039) in Patients With Hepatic Impairment Compared to Matched Healthy Subjects

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