Lurasidone Pediatric Pharmacokinetics Study
Condition: Schizophrenia; Autism
MeSH terms: Schizophrenia
Intervention: Lurasidone
Intervention description: Lurasidone 20, 40,80, 120 or 160 mg/day oral single and multiple does of lurasidone for 12 days
Intervention MeSH terms: Lurasidone Hydrochloride
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 105.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Schizophrenia; autism; bipolar; Lurasidone; Latuda

Summary:

      This is a Phase 1, open-label, multicenter, single and multiple ascending lurasidone dose
      study in subjects from 6 to 17 years old with schizophrenia spectrum, bipolar spectrum,
      autistic spectrum disorder, or other psychiatric disorders.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must provide written informed consent, if emancipated, written assent and be
             willing to participate in the study. Written informed consent from parent(s) or legal
             guardian(s) with sufficient intellectual capacity to understand the study and support
             subjects' adherence to the study procedures must be obtained for subjects who are not
             emancipated.

          -  Male or female subjects 6 to 17 years of age, inclusive. Subject must be 17 years or
             less at the follow-up visit.

          -  Subject is judged by the investigator to be clinically stable (ie, no psychiatric
             hospitalization within the past 12 weeks; no imminent risk of suicide or injury to
             self, others or property; no recent addition, or change in dosage, of psychotropic
             medication intended for the treatment of the primary psychiatric condition in the past
             4 weeks) but symptomatic (ie, some active symptoms of the primary psychiatric
             condition are present for which an atypical antipsychotic agent is judged to be an
             acceptable treatment option).

          -  Subjects with the following diagnoses will be eligible for participation: primary
             schizophrenia spectrum diagnosis (schizophrenia, schizoaffective, schizophreniform or
             psychotic disorder Not Otherwise Specified (NOS), bipolar spectrum disorder (bipolar
             I, II or bipolar NOS), pervasive developmental disorder (PDD) including autistic
             spectrum disorder (autistic disorder, Asperger's syndrome, or Pervasive Developmental
             Disorder-Not Otherwise Specified (PDD-NOS), attention-deficit hyperactivity (ADHD)
             with aggressive behavior [meeting co-morbid diagnostic criteria for Conduct
             Disorder/Disruptive Behavior Disorders Not Otherwise Specified (CD/DBD NOS), or
             Tourette's syndrome, via clinical interview (using MINI-Kid plus diagnostic interview
             and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition Text
             Revision (DSM-IV-TR) as a reference). Autistic disorder should also be confirmed by
             the Autism Diagnostic Interview, Revised (ADI-R).

          -  Within 5th to 95th percentile for gender specific weight-for-age and height-for-age
             Growth Charts from National Center for Health Statistics.

          -  No clinically relevant abnormal laboratory values.

          -  No clinically relevant abnormal vital sign values/findings.

          -  Females who participate in this study:

          -  are unable to become pregnant (eg, premenarchal, surgically sterile etc) -OR-

          -  are willing to remain sexually abstinent (not engage in sexual intercourse) from Day 1
             to 30 days after discharge on Day 11; -OR-

          -  are sexually active and willing to use an effective method of birth control (eg, male
             using condom and female using condom, diaphragm, contraceptive sponge, spermicide,
             contraceptive pill, or intrauterine device) from Day -1 to 30 days after discharge on
             Day 11.

          -  Males must be willing to remain sexually abstinent or use an effective method of birth
             control (eg, condom) from Day -1 to 30 days after discharge on Day 11.

          -  Willing and able to remain off any antipsychotic medication other than lurasidone for
             the duration of the study, if, in the investigator's opinion the subject is not at
             risk for worsening symptoms.

          -  Willing and able to swallow the size and number of lurasidone tablets specified per
             protocol.

          -  Willing and able to adhere to protocol-specified meal requirements during dosing.

          -  Have a stable living arrangement for at least 3 months prior to Day -1 and agrees to
             return to a similar living arrangement after discharge on Day 11. Homeless subjects
             may not be enrolled.

        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.