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

• Register: ClinicalTrials.gov
• Last refreshed on: 11 January 2021
• Main ID: NCT03048448
• Date of registration: 27/01/2017
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Pharmacokinetics of Fevipiprant (QAW039) in Patients With Hepatic Impairment Compared to Matched Healthy Subjects
• Scientific 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
• Date of first enrolment: May 31, 2017
• Target sample size: 42
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03048448
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Romania, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion 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, ?-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, ? 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.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hepatic Impairment

Intervention(s)

Drug: Fevipiprant

Primary Outcome(s)

Pharmacokinetics: Plasma concentration of Fevipiprant by AUClast [Time Frame: 120 hours post-dose]

Pharmacokinetics: Plasma concentration of Fevipiprant by AUCinf [Time Frame: 120 hours post-dose]

Pharmacokinetics: Plasma concentration of Fevipiprant by Cmax [Time Frame: 120 hours post-dose]

Secondary Outcome(s)

Relationship between plasma pharmacokinetics of Fevipiprant by AUCinf and baseline hepatic function. [Time Frame: 120 hours post-dose]

Pharmacokinetics of the metabolite CCN362 by AUClast [Time Frame: 120 hours post-dose]

Relationship between plasma pharmacokinetics of Fevipiprant by AUClast and baseline hepatic function. [Time Frame: 120 hours post-dose]

Pharmacokinetics of the metabolite CCN362 by Cmax [Time Frame: 120 hours post-dose]

Pharmacokinetics of the metabolite CCN362 by AUCinf [Time Frame: 120 hours post-dose]

Relationship between plasma pharmacokinetics of Fevipiprant by Cmax and baseline hepatic function. [Time Frame: 120 hours post-dose]

Secondary ID(s)

CQAW039A2108

Source(s) of Monetary Support

Please refer to primary and secondary sponsors