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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: Iloperidone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iloperidone<br>Eligible subjects receive a single oral dose of 2 mg iloperidone as a tablet | Drug: Iloperidone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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 . | 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. | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Blood and urine samples will be collected and plasma and urine concentrations of metabolite 88 will be measured | 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 | 
| Maximum plasma concentration following drug administration (Cmax) of iloperidone metabolites P88 | Blood and urine samples will be collected and plasma and urine concentrations of metabolite 88 will be measured | 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 metabolites P88 (CLr) | Blood samples will be collected and protein binding of metabolite 88 will be measured | 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 Curve (AUC) of iloperidone metabolite P95 | Blood and urine samples will be collected and plasma and urine concentrations of metabolite 95 will be measured | 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 P95 | Blood and urine samples will be collected and plasma and urine concentrations of metabolite 95 will be measured | 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 | 
| Maximum plasma concentration following drug administration (Cmax) of iloperidone metabolites P95 | Blood and urine samples will be collected and plasma and urine concentrations of metabolite 95 will be measured | 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 metabolites P95 | Blood samples will be collected and protein binding of metabolite 95 will be measured | 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 | 
| Number of participants with adverse events | Adverse events will be determined by evaluating clinical, laboratory evaluations, impact on vital signs and impacts on Electrocardiograms (ECGs) | Day 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic impairment, Iloperidone, ILO522D, Pharmacokinetics