Lurasidone Pediatric Pharmacokinetics Study

Exclusion Criteria

• •Clinically significant neurological, metabolic (including type 1 diabetes), hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, carcinoma, and/or urological disorder such as unstable angina, congestive heart failure (uncontrolled), or central nervous system (CNS) infection that would pose a risk to the subjects if they were to participate in the study or that might confound the results of the study.
• •Note: Active medical conditions that are minor or well-controlled are not exclusionary if they do not affect risk to the subject or the study results. In cases in which the impact of the condition upon risk to the subject or study results is unclear, the Medical Monitor should be consulted. Any subject with a known cardiovascular disease or condition (even if under control) must be discussed with the Medical Monitor before being enrolled to the study.
• •Evidence of any chronic organic disease of the CNS such as tumors, inflammation, active seizure disorder, vascular disorder, Parkinson's disease, or other forms of dementia, myasthenia gravis, or other degenerative processes. In addition, subjects must not have a history of mental retardation or persistent neurological symptoms attributable to serious head injury. Past history of febrile seizure, drug-induced seizure, or alcohol withdrawal seizure is not exclusionary.
• •Known presence or history of hepatic insufficiency or subject's estimated creatinine clearance is \< 80 mL/min/1.73 m2 by the following Bedside Schwartz equation for use with creatinine methods with calibration traceable to isotope dilution mass spectrometry (IDMS): Creatinine clearance (mL/min/1.73 m2) = (0.41 height) / serum creatinine concentration, where height in cm and serum creatinine in mg/dL.
• •Clinically significant finding(s) on physical examination determined by the investigator to pose a health concern to the subject while on study.
• •A history or presence of abnormal ECG, which in the investigator's opinion is clinically significant. Screening ECGs will be centrally over-read, and eligibility will be determined based on the over-read.
• •Known history or presence of clinically significant intolerance to any antipsychotic medications including but not limited to angioedema, serotonin or neuroleptic malignant syndromes, moderate to severe dystonia, or moderate to severe tardive dyskinesia.
• •Clinically significant alcohol abuse/dependence or drug abuse/dependence based on MINI-Kid criteria within the last 6 months prior to screening.
• •Clinically significant orthostatic hypotension (ie, a drop in systolic blood pressure of 20 mmHg or more and/or drop in diastolic blood pressure of 10 mmHg or more within 3 minutes of standing up).
• •Presence or history (within the last year) of a medical or surgical condition (eg, gastrointestinal disease) that might interfere with the absorption, metabolism, or excretion of orally administered lurasidone.
• •Positive breath alcohol test at screening or on Day -1.
• •Positive test results at screening or on Day -1 for:
• •Urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencyclidine, cannabinoids, and methadone). However, a positive test for amphetamines, barbiturates, opiates, benzodiazepines or methadone may not result in exclusion of subjects if the investigator determines that the positive test is as a result of prescription medicine(s).
• •Pregnancy test (only in female subjects ≥ 8 years old).
• •Lifetime history of human immunodeficiency virus (HIV) positive or acquired immune deficiency syndrome (AIDS), or history of Hepatitis B or C, or a positive test for Hepatitis B or C at screening (for subjects without a history).
• •Participated in another clinical trial or receiving an investigational product within 30 days prior to study drug administration.
• •Use of any inhibitor or inducer of CYP3A4 taken within 28 days prior to drug administration and until discharge on Day 11. Exceptions (eg, for grapefruit juice consumption) may be discussed on a case-by-case basis with the medical monitor.
• •Use of concomitant medications that consistently prolong the QT/QTc interval within 28 days prior to Day -1 to follow-up.
• •Received depot neuroleptics unless the last injection was at least 1 month or 1 treatment cycle prior to Screening, whichever is longer.
• •Received treatment with antidepressants within 3 days, fluoxetine or olanzapine plus fluoxetine combination within 28 days, MAO inhibitors within 14 days prior to Day -1 to follow-up.
• •Use of any antipsychotic medication (other than study drug), carbamazepine, oxcarbazepine or fluvoxamine, within 3 days prior to Day -1 (7 days prior to Day -1 for aripiprazole) and until follow-up.
• •Does not tolerate venipuncture or has any bleeding disorder that would complicate blood drawing.
• •Females who are pregnant, lactating, or likely to become pregnant during the study.
• •Donation or loss of whole blood within 60 days prior to drug administration.
• •Has a prolactin concentration greater than or equal to 100 ng/mL at screening.
• •Unwilling to abstain from vigorous exercise from Days -1 to 1 and from Days 9 to 10.
• •Subject answers "yes" to "Suicidal Ideation" Items 4 or 5 on the C-SSRS.
• •Subject is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property during the study. Subject has a history of one or more serious suicide attempts (based on the investigator's judgment) in the 12 months prior to screening. Subjects determined to be at risk of suicide or injury, as assessed by the investigator at screening, will be referred for further psychiatric evaluation.
• •Clinically relevant history of drug hypersensitivity to lurasidone or any components in the formulation.