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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Fevipiprant

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Novartis Investigative Site
  • Florida
    • Orlando, Florida, United States, 32809
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fevipiprant 450mg; 450mg Film Coated Tablet	Drug: Fevipiprant; Single 450mg dose; Other Names: QAW039

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	120 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	120 hours post-dose
Pharmacokinetics: Plasma concentration of Fevipiprant by Cmax	Cmax is the observed maximum plasma concentration following drug administration	120 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	120 hours post-dose
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	120 hours post-dose
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	120 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	120 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	120 hours post-dose
Pharmacokinetics of the metabolite CCN362 by Cmax	Cmax is the observed maximum plasma concentration following drug administration	120 hours post-dose

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CQAW039A2108 from the Novartis Clinical Trials Website
• A Plain Language Trial Summary is available on novartisclinicatrials.com

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2017
• Primary Completion (Actual): April 22, 2019
• Study Completion (Actual): April 22, 2019

Study Registration Dates

• First Submitted: January 27, 2017
• First Submitted That Met QC Criteria: February 7, 2017
• First Posted (Estimate): February 9, 2017

Study Record Updates

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

More Information

Terms related to this study

• Keywords: pharmacokinetics; Fevipiprant,; adults,; Hepatic impairment,
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: CQAW039A2108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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