Clinical trial NCT01529294: Single-dose Iloperidone Pharmacokinetics in Patients With Mild or Moderate Liver Disease, Compared to Healthy Volunteers
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic impairment
Iloperidone
ILO522D
Pharmacokinetics
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-02-08
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

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


Eligibility 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

Primary outcomes:
measure: Measure: Area Under Curve (AUClast, AUCinf) and maximum concentration (Cmax)
timeFrame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose
measure: Maximum plasma concentration following drug administration (Cmax) of iloperidone
timeFrame: 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
measure: Protein binding of iloperidone
timeFrame: 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
measure: Area under the plasma concentration-time Curve from time zero to infinity (AUCinf) of iloperidone
timeFrame: 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:
measure: Area Under the plasma Curve (AUC) of iloperidone metabolite P88
timeFrame: 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
measure: 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.
timeFrame: 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
measure: Maximum plasma concentration following drug administration (Cmax) of iloperidone metabolites P88
timeFrame: 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
measure: Protein binding of iloperidone metabolites P88 (CLr)
timeFrame: 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
measure: Area Under the plasma Curve (AUC) of iloperidone metabolite P95
timeFrame: 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
measure: Area under the plasma concentration-time Curve from time zero to infinity (AUCinf) of iloperidone metabolite P95
timeFrame: 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
measure: Maximum plasma concentration following drug administration (Cmax) of iloperidone metabolites P95
timeFrame: 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
measure: Protein binding of iloperidone metabolites P95
timeFrame: 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
measure: Number of participants with adverse events
timeFrame: Day 6
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Novartis Investigative Site
state: California
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
city: South Miami
country: United States
facility: Novartis Investigative Site
state: Florida
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: