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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: Fevipiprant


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fevipiprant 450mg<br>450mg Film Coated Tablet | Drug: Fevipiprant<br>* Single 450mg dose<br>* Other names: QAW039;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic impairment,, Fevipiprant,, adults,, pharmacokinetics