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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01529294
First received: September 23, 2011
Last updated: March 13, 2013
Last verified: March 2013
  Purpose

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 Intervention Phase
Hepatic Impairment
Drug: Iloperidone
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Measure: Area Under Curve (AUClast, AUCinf) and maximum concentration (Cmax) [ Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose ] [ Designated as safety issue: No ]
    Pharmacokinetics of iloperidone in subjects with mild or moderate hepatic impairment, compared to healthy volunteers.

  • Maximum plasma concentration following drug administration (Cmax) of iloperidone [ 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 ] [ Designated as safety issue: No ]
    Blood and urine samples will be collected and plasma and urine concentration will be measured.

  • Protein binding of iloperidone [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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. [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    Blood samples will be collected and protein binding of metabolite 88 will be measured

  • Area Under the plasma Curve (AUC) of iloperidone metabolite P95 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    Blood and urine samples will be collected and plasma and urine concentrations of metabolite 95 will be measured

  • Protein binding of iloperidone metabolites P95 [ 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 ] [ Designated as safety issue: No ]
    Blood samples will be collected and protein binding of metabolite 95 will be measured

  • Number of participants with adverse events [ Time Frame: Day 6 ] [ Designated as safety issue: Yes ]
    Adverse events will be determined by evaluating clinical, laboratory evaluations, impact on vital signs and impacts on Electrocardiograms (ECGs)


Enrollment: 90
Study Start Date: August 2010
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Iloperidone
Eligible subjects receive a single oral dose of 2 mg iloperidone as a tablet
Drug: Iloperidone

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01529294

Locations
United States, California
Novartis Investigative Site
Anaheim, California, United States, 92801
United States, Florida
Novartis Investigative Site
Miami, Florida, United States, 33169
Novartis Investigative Site
Orlando, Florida, United States, 32809
Novartis Investigative Site
South Miami, Florida, United States, 33143
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01529294     History of Changes
Other Study ID Numbers: CILO522D2401
Study First Received: September 23, 2011
Last Updated: March 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Hepatic impairment
Iloperidone
ILO522D
Pharmacokinetics

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on October 22, 2014