Multiple sclerosis (MS) (study conducted in volunteers with normal hepatic function or mild/moderate hepatic impairment) Not Applicable
Conditions
Interventions
Cohort 1: Participants with normal hepatic function will receive a single dose of fenebrutinib, 200 milligrams (mg), orally, on Day 1.
Cohort 2: Participants with mild hepatic impairment will receive
Sponsors
Genentech Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female participants between 18 to 75 years of age, inclusive, at screening 2. Body weight =45 kilograms (kg) and within body mass index (BMI) range 18.0 to 42.0 kilograms per square meter (kg/m2), inclusive Additional inclusion criteria for participants with normal hepatic function (Cohort 1) only: 1. In reasonably good health for their age 2. Matched to participants with mild or moderate hepatic impairment in sex, age (±10 years), and body weight (±15%) 3. Negative hepatitis panel 4. Normal hepatic function and no history of clinically significant hepatic dysfunction 5. Estimated glomerular filtration rate =80 millilitre per minute (mL/min) at screening, as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. Additional inclusion criteria for participants with hepatic impairment (Cohorts 2 and 3) only: 1. Chronic (>6 months), stable (no acute episodes of illness within the previous 1 month prior to Screening due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology. Participants must also remain stable throughout the Screening period. 2. Considered to have mild or moderate hepatic impairment and has been clinically stable for at least 1 month prior to Screening. To be classified as having hepatic impairment, participants must have a Child-Pugh score of 5 to 6 (inclusive; mild) or 7 to 9 (inclusive; moderate) with known medical history of liver disease and unambiguous medical history. 3. Negative hepatitis B virus core antibody and HbsAg screens and negative hepatitis C viral load. 4. Estimated glomerular filtration rate =60 mL/min at screening, as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. Other protocol defined inclusion criteria could apply.
Exclusion criteria
Exclusion criteria: 1. Participants who are pregnant or breastfeeding or intending to become pregnant during the study or within 28 days after the dose of study drug. 2. History of surgical or artificial shunts (i.e., transjugular intrahepatic portosystemic procedure). 3. History of malignancy within 5 years prior to screening, except for completely excised basal cell carcinoma or squamous cell carcinoma of the skin or cervical carcinoma in situ. 4. Significant illness, including infections, surgery, or hospitalization within the 2 weeks prior to dosing. 5. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs, except that uncomplicated hernia repair, appendectomy, and/or cholecystectomy will be allowed. 6. Malabsorption syndrome or other condition that would interfere with enteral absorption. Additional exclusion criteria for participants with hepatic impairment (Cohorts 2 and 3) only: 1. Evidence of progressive liver disease that has worsened or is worsening within 1 month prior to Screening. 2. Evidence of hepatorenal syndrome 3. Ascites requiring paracentesis within 3 months prior to Check-in (Day -1) or other intervention, with the exception of diuretics. 4. Required treatment for gastrointestinal bleeding within 12 months prior to Check-in (Day -1) 5. Receipt of a liver transplant 6. Required additional medication for hepatic encephalopathy within 12 months prior to check-in (Day -1), unless deemed acceptable by the investigator. 7. One or more of the following laboratory results: • Alkaline phosphatase >10 × upper limit of normal (ULN). • Alanine aminotransferase or aspartate aminotransferase >5 × ULN. • Bilirubin >3 × ULN in the absence of Gilbert’s Syndrome or hemolysis. Other protocol defined exclusion criteria could apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Area under the concentration-time curve from hour 0 to the last measurable concentration (AUC0-t) of fenebrutinib measured using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay from the blood samples collected at multiple time points from Day 1 to Day 5 2. AUC extrapolated to infinity (AUC0-8) of fenebrutinib measured using a validated LC-MS/MS assay from the blood samples collected at multiple time points from Day 1 to Day 5 3. Maximum observed concentration (Cmax) of fenebrutinib measured using a validated LC-MS/MS assay from the blood samples collected at multiple time points from Day 1 to Day 5 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Number of participants with adverse events (AEs) and severity of AEs graded as per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE; v5.0) from screening up to 14 days after the dose of study drug (approximately 6 weeks) | — |
Countries
Canada, New Zealand
Contacts
Public ContactClinical Trials
Outcome results
None listed