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

Novartis Pharmaceuticals90 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Masking

NONE

Enrollment

Conditions

Hepatic Impairment

Interventions

IloperidoneDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (4)

Novartis Investigative Site

Anaheim, California, United States

Novartis Investigative Site

Miami, Florida, United States

Novartis Investigative Site

Orlando, Florida, United States

Novartis Investigative Site

South Miami, Florida, United States

Outcomes

Primary Outcomes

Measure: Area Under Curve (AUClast, AUCinf) and maximum concentration (Cmax)

Pharmacokinetics of iloperidone in subjects with mild or moderate hepatic impairment, compared to healthy volunteers.

Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose

Maximum plasma concentration following drug administration (Cmax) of iloperidone

Blood and urine samples will be collected and plasma and urine concentration will be measured.

Time frame: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose, and from pre-dose to 48 hours post-dose

Protein binding of iloperidone

Blood samples will be collected and protein binding will be measured .

Time frame: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose, and from pre-dose to 48 hours post-dose

Area under the plasma concentration-time Curve from time zero to infinity (AUCinf) of iloperidone

Blood and urine samples will be collected and plasma and urine concentration will be measured.

Time frame: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose, and from pre-dose to 48 hours post-dose

Secondary Outcomes

Area Under the plasma Curve (AUC) of iloperidone metabolite P88

Blood and urine samples will be collected and plasma and urine concentrations of metabolite 88 will be measured

Time frame: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose and from pre-dose to 48 hours post-dose

Area under the plasma concentration-time Curve from time zero to infinity (AUCinf) of iloperidone metabolite P88 records, listed by subject. Summary statistics provided by impairment group and visit/time.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.