Pediatric Schizophrenia Efficacy and Safety Study
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Lurasidone 40 mg; Lurasidone 80 mg; Placebo 40 or 80 mg
Intervention description: Lurasidone 40 mg once daily; Lurasidone 80 mg once daily; Placebo 40 or 80 mg once daily
Intervention MeSH terms: Lurasidone Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 327.0
Sex: All
Minimum age: 13 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: schizophrenia; Lurasidone; Latuda

Summary:

      Efficacy and Safety study of Lurasidone in pediatric patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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. In accordance
             with Institutional Review Board (IRB) requirements, the subject will complete an
             informed assent prior to study participation.

          -  Male or female subjects 13 to 17 years of age, inclusive, at the time of consent.

          -  DSM-IV-TR axis I primary diagnosis of schizophrenia (including disorganized (295.10),
             paranoid (295.30), undifferentiated (295.90) subtypes) and confirmation of the
             schizophrenia diagnosis by an adequately trained clinician at the time of screening,
             by means of the Schedule for Affective Disorders and Schizophrenia for School-age
             Children (K-SADS-PL).

          -  PANSS total score ≥ 70 at screening and Baseline.

          -  CGI-S ≥ 4 at screening and Baseline.

          -  Within 5th to 95th percentile for gender specific weight-for-age and height-for-age
             Growth Charts from National Center for Health Statistics.

          -  In good physical health on the basis of medical history, physical examination, and
             laboratory screening.

          -  Females who participate in this study:

        are unable to become pregnant (eg, premenarchal, surgically sterile, etc.); -OR-

        practices true abstinence (consistent with lifestyle) and must agree to remain abstinent
        from signing informed consent to at least 30 days after the last dose of study drug has
        been taken;

        -OR-

        are sexually active and willing to use a medically effective method of birth control (e.g.,
        male using condom and female using condom, diaphragm, contraceptive sponge, spermicide,
        contraceptive pill, or intrauterine device) from signing informed consent to at least 7
        days after the last dose of study drug has been taken.

          -  Males must be willing to remain sexually abstinent (consistent with lifestyle) or 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 signing informed consent to at least 30 days after the last dose of study
             drug has been taken.

          -  In the judgement of the clinician, the subject has an acute exacerbation of psychotic
             symptoms (no longer than 2 months in duration) and marked deterioration of function
             from baseline (by history) or, the subject has been hospitalized for the purpose of
             treating an acute psychotic exacerbation for 2 consecutive weeks or less immediately
             before screening.

          -  In the judgment of the investigator, the subject is able to swallow the size and
             number of study drug tablets specified per protocol.

          -  Willing and able to adhere to protocol-specified meal requirements during dosing.

        Exclusion Criteria:

          -  Has an Axis I or Axis II diagnosis other than schizophrenia that has been the primary
             focus of treatment within 3 months of screening.

          -  Has a history or current diagnosis of mental retardation, neuroleptic malignant
             syndrome, or any neurologic disorder, or severe head trauma.

          -  Lifetime history of human immunodeficiency virus (HIV) positive or acquired immune
             deficiency syndrome (AIDS), or history of Hepatitis B or C.

          -  Any of the following:

        Documented history of chromosomal disorder with developmental impairment (ie, trisomy
        chromosome 21; 22q11 deletion syndrome).

        Evidence of any chronic organic disease of the CNS such as tumors, inflammation, active
        seizure disorder, vascular disorder, potential CNS related disorders that might occur in
        childhood- eg, Duchenne Muscular dystrophy, myasthenia gravis, or other neurologic or
        serious neuromuscular disorders. In addition, subjects must not have a history of
        persistent neurological symptoms attributable to serious head injury. Past history of
        febrile seizure, drug-induced seizure, or alcohol withdrawal seizure is not exclusionary.

          -  PANSS total scores ≥ 120 at screening or Baseline.

          -  Exhibits evidence of moderate or severe extrapyramidal symptoms, dystonia, tardive
             dyskinesia, or any other moderate or severe movement disorder. Severity to be
             determined by the investigator.

          -  Lifetime history of electroconvulsive therapy (ECT).

          -  Resistant to antipsychotic treatment based on at least two different prior adequate
             trials (ie, adequate dose and duration) of an antipsychotic agent within the current
             episode of schizophrenia.

          -  Clinically significant neurological, metabolic (including type 1 diabetes), hepatic,
             renal, hematological, pulmonary, cardiovascular, gastrointestinal, carcinoma, and/or
             urological disorder 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
        controlled) must be discussed with the Medical Monitor during screening.

          -  Has a history of malignancy < 5 years prior to signing the informed consent.

          -  Clinically significant finding(s) on physical examination determined by the
             investigator to pose a health concern to the subject while on study.

          -  Clinically relevant abnormal laboratory values or abnormal vital sign values/findings.

        Note: If any laboratory results are outside the normal range, the site may have the subject
        retested. If upon retesting the value remains outside the normal range, the significance of
        this value must be discussed with the Medical Monitor for enrollment consideration.

          -  A history or presence of abnormal ECG, which in the investigator's opinion is
             clinically significant. Abnormal screening ECGs will be centrally over-read, and
             eligibility will be determined based on the over-read.

          -  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.

          -  Clinically significant alcohol abuse/dependence or drug abuse/dependence based on
             DSM-IV-TR criteria within the last 6 months prior to screening.

          -  Positive test results at screening or Baseline for:

               1. Urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine,
                  opiates, phencyclidine, cannabinoids, and methadone). 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 taking prescription medicine(s) as prescribed. In the event a
                  subject tests positive for cannabinoids (tetrahydrocannabinol) or alcohol, the
                  investigator will evaluate the subject's ability to abstain from prohibited
                  substances during the study. If in the investigator's clinical judgment the
                  subject will abstain, the subject may be enrolled after consultation with the
                  Medical Monitor.

               2. Pregnancy test.

          -  Females who are pregnant, lactating, or likely to become pregnant during the study.

          -  Participated in another interventional clinical trial or receiving an investigational
             product within 30 days prior to randomization.

          -  Donation of whole blood within 60 days prior to randomization.

          -  Known history or presence of clinically significant intolerance to any antipsychotic
             medications including but not limited to angioedema, serotonin or neuroleptic
             malignant syndromes.

          -  Clinically relevant history of drug hypersensitivity to lurasidone or any components
             in the formulation.

          -  Use of concomitant medications that consistently prolong the QT/QTc interval within 28
             days prior to randomization.

          -  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, stimulants, or atomoxetine within 3 days
             prior to randomization, fluoxetine hydrochloride within 21 days of randomization,
             monoamine oxidase (MAO) inhibitor within 28 days of randomization, or clozapine within
             120 days of randomization.

          -  Use of any antipsychotic medication (other than study drug), carbamazepine,
             oxcarbazepine, eslicarbazepine acetate, or fluvoxamine, within 3 days prior to
             randomization (7 days prior to randomization for aripiprazole) and until follow-up.

          -  Has a prolactin concentration ≥ 100 ng/mL at screening, or has a history of pituitary
             adenoma.

          -  At screening or Baseline the 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 3 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.

          -  Adhering to a special diet for the 28 days prior to drug administration (eg, liquid,
             protein, raw food diet).

          -  Subject is planning to move during the study, is chronically homeless, or is unable to
             attend all planned study visits. The Medical Monitor will be consulted for individual
             cases, as needed.

          -  Demonstrates a decrease (improvement) of > 25% in the PANSS score between screening
             and Baseline visits.

          -  Subject with newly diagnosed Type 2 diabetes during screening. A subject with Type 2
             diabetes is eligible for study inclusion if considered clinically stable, which is
             defined as:

        Random (non-fasting) screening glucose is < 200 mg/dl (11.1 mmol/L); and If ≥ 200 mg/dL
        (11.1 mmol/L) must be retested in a fasted state. Retested fasted value cannot be ≥ 126
        mg/dL.

        HbA1c ≤ 6.5%; and If a subject is currently being treated with oral anti-diabetic
        medication(s), the dose must have been stable for at least 4 weeks prior to screening. Such
        medication may be adjusted or discontinued during the study, as clinically indicated.

          -  Subject has required hospitalization for diabetes or related complications in the past
             12 months.

          -  Subject requires use of concomitant medications that are potent inducers or inhibitors
             of the cytochrome P450 (CYP) 3A4 enzyme system (Appendix C) from signing informed
             consent until follow-up.

          -  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 4
             minutes of standing up).