Impaired hepatic function Digestive System
Conditions
Interventions
Participants with normal hepatic function and mild, moderate and severe hepatic impairment will receive a single dose of RO7223280, 600 mg, administered as an IV infusion on Day 1.
Pa
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female participants aged 18 to 75 years of age, inclusive, at screening 2. Participants must have a body weight of at least 50 kg and a body mass index (BMI) within the range of 18 to 40 kg/m² (inclusive) Additional inclusion criteria for participants with normal hepatic function: 3. Participants must be in reasonably good health as determined by the Investigator 4. Matched to participants with mild, moderate, or severe hepatic impairment in sex, age (± 10 years), and BMI (± 15%) Additional inclusion criteria for participants with hepatic impairment only: 5. Documented chronic stable liver disease (Child-Pugh class A, B, or C, at screening); diagnosis of cirrhosis due to parenchymal liver disease. This will exclude biliary liver cirrhosis or other causes of hepatic impairment not related to parenchymal disorder 6. Anemia secondary to hepatic disease will be acceptable, if hemoglobin =9 g/dL and anemia symptoms are not clinically significant as judged by the Investigator (or designee), Sponsor and Medical Monitor 7. Participants must have a platelet count =25,000/µL
Exclusion criteria
Exclusion criteria: 1. History or evidence of any medical conditions (e.g., gallbladder removal, malabsorption syndromes) potentially altering the absorption, distribution, metabolism, or elimination of drugs 2. History or presence of clinically significant electrocardiogram (ECG) abnormalities based on the average of the triplicate ECG recordings (e.g., PQ/PR interval >210 ms), QT corrected for heart rate using the Fridericia’s correction factor (QTcF) >480 ms or clinically significant cardiovascular disease (e.g., cardiac insufficiency, coronary artery disease with recent myocardial infarction within the past 2 months, clinically significant cardiomyopathy, decompensated congestive heart failure, family history of congenital long QT syndrome, family history of sudden death) 3. History of unstable diabetes mellitus (as evidenced by hemoglobin A1c =9.0% [75 mmol/mol] at screening) 4. Vaccination is prohibited within 1 month prior to Day 1 5. Minimal smoking (up to 10 cigarettes/day) may be allowed at the discretion of the Investigator in discussion with the Sponsor and Medical Monitor. Participants will not be permitted to smoke within 2 hours prior to dose or 4 hours post-dose on Day 1 6. Evidence of human immunodeficiency virus (HIV) infection and/or positive result for human HIV antibodies. 7. Evidence of hepatorenal syndrome and estimated creatinine clearance range <60 ml/min or clinically significant abnormal sodium and potassium levels 8. Participants with insufficient venous access 9. History of hypersensitivity to any of the excipients in the formulation of RO7223280 Additional inclusion criteria for participants with normal hepatic function 10. Acute diseases or medical/surgical procedure with clinical significance (determined by the Investigator) within 2 weeks prior to screening, including gastrointestinal [GI] diseases and infections (such as respiratory or central nervous system infections) 11. Significant history or clinical manifestation of hepatic disorder 12. History or presence of liver disease or liver injury 13. Presence of hepatitis B surface antigen or positive hepatitis C antibody test result Additional inclusion criteria for participants with hepatic impairment only: 14. Acute diseases or medical/surgical procedure with clinical significance (determined by the Investigator) within 2 weeks prior to screening, including GI diseases and infections (such as respiratory, central nervous system infections, or spontaneous bacterial peritonitis) 15. Current functioning organ transplant or are waiting for an organ transplant 16. Evidence of severe ascites 17. Presence of a portosystemic shunt, except for participants with severe hepatic impairment 18. Participants in current need for paracentesis within 1 month, prior to Day 1 19. History of GI hemorrhage due to esophageal varices or peptic ulcers less than 6 weeks prior to screening 20. History within 90 days prior to the screening visit or current symptoms of hepatic encephalopathy Grade 2 or above 21. Worsening of hepatic encephalopathy within 1 month prior to Day -1 22. Use of rifaximin for the treatment of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Maximum observed concentration (Cmax) of total and unbound RO7223280 measured using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay using plasma samples taken at multiple timepoints from Day 1 up to Day 4 2. Area under the plasma concentration versus time curve- extrapolated to infinity (AUCinf) of total and unbound RO7223280 measured using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay using plasma samples taken at multiple timepoints from Day 1 up to Day 4 3. AUC from zero to the last measurable concentration (AUClast) of total and unbound RO7223280 measured using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay using plasma samples taken at multiple timepoints from Day 1 up to Day 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time to maximum observed concentration (tmax) of RO7223280 measured using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay using plasma samples taken at multiple timepoints from Day 1 up to Day 4 2. Percentage of extrapolated area under the plasma concentration versus time curve extrapolated to infinity (AUC%extra) of RO7223280 measured using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay using plasma samples taken at multiple timepoints from Day 1 up to Day 4 3. Terminal rate constant (?z) of RO7223280 measured using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay using plasma samples taken at multiple timepoints from Day 1 up to Day 4 4. Apparent terminal elimination half-life (t1/2) of RO7223280 measured using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay using plasma samples taken at multiple timepoints from Day 1 up to Day 4 5. Total clearance (CL) of total and unbound RO7223280 measured using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay using plasma samples taken at multiple timepoints from Day 1 up to Day 4 6. Volume of distribution at steady-state (Vss) of total and unbound RO7223280 measured using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay using plasma samples taken at multiple timepoints from Day 1 up to Day 4 7. Molecular weight adjusted metabolite-to-parent ratio for Cmax and AUC of RO7223280 measured using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay using plasma samples taken at multiple timepoints from Day 1 up to Day 4 8. Number of participants with adverse events (AEs) recorded from screening to end of study (approximately 5 weeks) 9. Number of participants with severity of AEs det | — |
Countries
Germany, Poland, Slovakia
Contacts
Public ContactClinical Trials
Outcome results
None listed