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

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01529294
• Other study ID #: CILO522D2401
• Status: Completed
• Phase: Phase 1
• First received: September 23, 2011
• Last updated: March 13, 2013
• Start date: August 2010
• Est. completion date: July 2012

Study information

• Verified date: March 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Iloperidone

Locations

Country	Name	City	State
United States	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

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes