Clinical trial NCT03048448: Pharmacokinetics of Fevipiprant (QAW039) in Patients With Hepatic Impairment Compared to Matched Healthy Subjects
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic impairment,
Fevipiprant,
adults,
pharmacokinetics
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-02-09
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility 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, 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.

Primary outcomes:
measure: Pharmacokinetics: Plasma concentration of Fevipiprant by AUClast
timeFrame: 120 hours post-dose
measure: Pharmacokinetics: Plasma concentration of Fevipiprant by AUCinf
timeFrame: 120 hours post-dose
measure: Pharmacokinetics: Plasma concentration of Fevipiprant by Cmax
timeFrame: 120 hours post-dose
Secondary outcomes:
measure: Relationship between plasma pharmacokinetics of Fevipiprant by AUClast and baseline hepatic function.
timeFrame: 120 hours post-dose
measure: Relationship between plasma pharmacokinetics of Fevipiprant by AUCinf and baseline hepatic function.
timeFrame: 120 hours post-dose
measure: Relationship between plasma pharmacokinetics of Fevipiprant by Cmax and baseline hepatic function.
timeFrame: 120 hours post-dose
measure: Pharmacokinetics of the metabolite CCN362 by AUClast
timeFrame: 120 hours post-dose
measure: Pharmacokinetics of the metabolite CCN362 by AUCinf
timeFrame: 120 hours post-dose
measure: Pharmacokinetics of the metabolite CCN362 by Cmax
timeFrame: 120 hours post-dose
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Novartis Investigative Site
state: California
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: