Pharmacokinetic Study of Vorasidenib in Severe Hepatically Impaired and Matched-Control Participants

Inclusion Criteria13

• Participants with hepatic impairment:
• Diagnosis of cirrhosis due to parenchymal liver disease
• Considered to have a Child-Pugh score of 10 to 15, consistent with severe HI, and a documented medical history of liver disease. Participants must be clinically stable (no acute episodes of illness due to deterioration in hepatic function) for at least 1 month prior to screening and are likely to remain stable throughout the study.
• Grade 0 or Grade 1 hepatic encephalopathy considered stable per Investigator assessment without exacerbation within the 6 months prior to screening.
• Currently on a stable medication regimen, defined as not starting new drug(s) or significantly changing drug dosage(s) within 14 days preceding Day 1.
• Non-hepatic abnormal laboratory values must be not clinically significant as judged by the Investigator (or designee) and the study medical monitor.
• Anemia secondary to hepatic disease is acceptable if hemoglobin is ≥ 9 g/dL and anemia symptoms are not clinically significant. Platelet count must be ≥ 35,000 platelets.
• QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≤ 480 msec.
• Matched-control participants:
• Healthy, with normal hepatic function with a Child-Pugh score below 5.
• Resting blood pressure of 90 to 140 mmHg (systolic) and 40 to 90 mmHg (diastolic).
• QTcF of ≤ 450 msec.
• Participant must match hepatically impaired participants with respect to sex, race, age (±10 years), smoking status (smoke or vape ≤ 10 cigarettes/day), and body mass index (±20%).