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

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.

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.