Hepatic Impairment
Conditions
Keywords
Hepatic impairment,, Fevipiprant,, adults,, pharmacokinetics
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.
Interventions
DRUGFevipiprant
Single 450mg dose
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Pharmacokinetics of the metabolite CCN362 by Cmax | 120 hours post-dose | Cmax is the observed maximum plasma concentration following drug administration |
| 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 |
| 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 |
Countries
United States
Outcome results
None listed