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

NCT01529294 | Completed Phase 1

• 1 other identifier: CILO522D2401
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 4

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

Conditions

Hepatic Impairment

Keywords

Hepatic impairment; Iloperidone; ILO522D; Pharmacokinetics

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (9)

• 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

• 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

• 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

• 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

• 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

Study Arms (1)

Iloperidone

EXPERIMENTAL

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

Drug: Iloperidone

Interventions

Iloperidone DRUG

Iloperidone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Caucasian 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).
• good general health
• matched by age, gender, smoking status, Body Mass Index, and CYP2D6 phenotype to hepatic impaired subjects.

You may not qualify if:

• 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
• 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.
• History of alcohol abuse prior to dosing, or evidence of such abuse during screening.
• Pulse Rate \> 200 msec

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (4)

Novartis Investigative Site

Anaheim, California, 92801, United States

Location

Novartis Investigative Site

Miami, Florida, 33169, United States

Location

Novartis Investigative Site

Orlando, Florida, 32809, United States

Location

Novartis Investigative Site

South Miami, Florida, 33143, United States

Location

MeSH Terms

Interventions

iloperidone

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2011
• First Posted: February 8, 2012
• Study Start: August 1, 2010
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: March 14, 2013

Record last verified: 2013-03

Locations

US (4)