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

Phase 1

Completed

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.

Recruitment & Eligibility

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

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.

Arm && Interventions

Group	Intervention	Description
Fevipiprant 450mg	Fevipiprant	450mg Film Coated Tablet

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Relationship between plasma pharmacokinetics of Fevipiprant by AUClast and baseline hepatic function.	120 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 Child Pugh score
Relationship between plasma pharmacokinetics of Fevipiprant by AUCinf and baseline hepatic function.	120 hours post-dose	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.	120 hours post-dose	Cmax is the observed maximum plasma concentration following drug administration related to Child Pugh score
Pharmacokinetics of the metabolite CCN362 by AUClast	120 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	120 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	120 hours post-dose	Cmax is the observed maximum plasma concentration following drug administration

Locations (1): Novartis Investigative Site
🇺🇸
Orlando, Florida, United States