Single-dose Iloperidone Pharmacokinetics in Patients With Mild or Moderate Liver Disease, Compared to Healthy Volunteers
- Registration Number
- NCT01529294
- Lead Sponsor
- Novartis Pharmaceuticals
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 90
- 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 (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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Iloperidone Iloperidone Eligible subjects receive a single oral dose of 2 mg iloperidone as a tablet
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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 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)
Trial Locations
- Locations (1)
Novartis Investigative Site
🇺🇸South Miami, Florida, United States