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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- Measure: Area Under Curve (AUClast, AUCinf) and maximum concentration (Cmax)
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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
- •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
Arms & Interventions
Iloperidone
Eligible subjects receive a single oral dose of 2 mg iloperidone as a tablet
Intervention: Iloperidone (Drug)
Outcomes
Primary Outcomes
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
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
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
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
Blood and urine samples will be collected and plasma and urine concentration will be measured.
Secondary Outcomes
- 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)
- 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)
- 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)
- 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)
- Number of participants with adverse events(Day 6)