Hepatic Impairment
Conditions
Keywords
Hepatic impairment, Iloperidone, ILO522D, Pharmacokinetics
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
Interventions
DRUGIloperidone
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 |
| 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) |
Countries
United States
Outcome results
None listed