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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01529294

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

22.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hepatic Impairment	Drug: Iloperidone	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

90 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Official Title:

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

Study Start Date :

Aug 1, 2010

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Iloperidone Eligible subjects receive a single oral dose of 2 mg iloperidone as a tablet	Drug: Iloperidone

Arm

Intervention/Treatment

Experimental: Iloperidone

Eligible subjects receive a single oral dose of 2 mg iloperidone as a tablet

Drug: Iloperidone

Outcome Measures

Primary Outcome Measures

Measure: Area Under Curve (AUClast, AUCinf) and maximum concentration (Cmax) [predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose]
Pharmacokinetics of iloperidone in subjects with mild or moderate hepatic impairment, compared to healthy volunteers.
Maximum plasma concentration following drug administration (Cmax) of iloperidone [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]
Blood and urine samples will be collected and plasma and urine concentration will be measured.
Protein binding of iloperidone [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]
Blood samples will be collected and protein binding will be measured .
Area under the plasma concentration-time Curve from time zero to infinity (AUCinf) of iloperidone [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]
Blood and urine samples will be collected and plasma and urine concentration will be measured.

Secondary Outcome Measures

Area Under the plasma Curve (AUC) of iloperidone metabolite P88 [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]
Blood and urine samples will be collected and plasma and urine concentrations of metabolite 88 will be measured
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. [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]
Blood and urine samples will be collected and plasma and urine concentrations of metabolite 88 will be measured
Maximum plasma concentration following drug administration (Cmax) of iloperidone metabolites P88 [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]
Blood and urine samples will be collected and plasma and urine concentrations of metabolite 88 will be measured
Protein binding of iloperidone metabolites P88 (CLr) [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]
Blood samples will be collected and protein binding of metabolite 88 will be measured
Area Under the plasma Curve (AUC) of iloperidone metabolite P95 [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]
Blood and urine samples will be collected and plasma and urine concentrations of metabolite 95 will be measured
Area under the plasma concentration-time Curve from time zero to infinity (AUCinf) of iloperidone metabolite P95 [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]
Blood and urine samples will be collected and plasma and urine concentrations of metabolite 95 will be measured
Maximum plasma concentration following drug administration (Cmax) of iloperidone metabolites P95 [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]
Blood and urine samples will be collected and plasma and urine concentrations of metabolite 95 will be measured
Protein binding of iloperidone metabolites P95 [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]
Blood samples will be collected and protein binding of metabolite 95 will be measured
Number of participants with adverse events [Day 6]
Adverse events will be determined by evaluating clinical, laboratory evaluations, impact on vital signs and impacts on Electrocardiograms (ECGs)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Anaheim	California	United States	92801
2	Novartis Investigative Site	Miami	Florida	United States	33169
3	Novartis Investigative Site	Orlando	Florida	United States	32809
4	Novartis Investigative Site	South Miami	Florida	United States	33143