Single-dose Iloperidone Pharmacokinetics in Patients With Mild or Moderate Liver Disease, Compared to Healthy Volunteers

Open-label, Single-dose, Parallel-group Study to Compare the PKs of Iloperidone in Subjects With Mild or Moderate Hepatic Impairment With That in Matched Healthy Control Subjects

This study aims to determine the pharmacokinetic profile and the tolerability of iloperidone in subjects with mild or moderate hepatic impairment comparatively to healthy matched subjects

Inclusion Criteria:

• Inclusion criteria (all subjects):
• Caucasian subjects
• Inclusion criteria (hepatic impaired subjects):
• subjects with physical signs consistent with a clinical diagnosis of stable liver disease, which has been confirmed by imaging techniques, ultrasound, Magnetic Resonance Imaging or Computed Tomogram within 3 months of screening, and a creatinine clearance > 50 mL/min (based on Cockroft and Gault formula).
• Inclusion criteria (healthy volunteers):
• good general health
• matched by age, gender, smoking status, Body Mass Index, and CYP2D6 phenotype to hepatic impaired subjects.

Exclusion Criteria:

• Exclusion criteria (all subjects):
• Subjects who report smoking a pipe, cigars or more than 20 cigarettes per day .
• History of drug abuse as defined in Diagnostic and Statistical Manual of Mental Disorders, Diagnostic Criteria for Drug and Alcohol Abuse, within the 12 months prior to screening
• History of first-dose response/syncope to alpha1-blocking agents
• Exclusion criteria (Hepatic impaired subjects):
• Patients with symptoms or 6 months past history of encephalopathy.
• Patients with clinical evidence of moderate-severe ascites.
• Patients having a previous surgical porto-systemic shunt.
• Exclusion criteria (Healthy volunteers):
• History of alcohol abuse prior to dosing, or evidence of such abuse during screening.
• Pulse Rate > 200 msec

Other protocol-defined inclusion/exclusion criteria may apply