Lurasidone Pediatric Autism Study
Condition: Autism
MeSH terms: Autistic Disorder
Intervention: Lurasidone 20 mg daily; Lurasidone; Placebo
Intervention description: Lurasidone 20 mg once daily; Lurasidone 60 mg once daily; Placebo
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: 150.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Autism, Lurasidone, Latuda

Summary:

      This is a randomized, double-blind, placebo-controlled study designed to evaluate the
      efficacy and safety of 2 fixed doses of lurasidone (20 mg/day and 60 mg/day) for 6 weeks
      compared with placebo in pediatric and adolescent subjects with irritability associated with
      autistic disorder who reside in the community setting.
    

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 when developmentally appropriate, to participate in the study before
             conduct of any study-specific procedures.

          -  Male or female subjects 6 to 17 years of age, inclusive, at the time of consent.

          -  A reliable informant (eg, parent, legal guardian, or caregiver) who has past and
             current direct knowledge of the subject must accompany the subject at each visit and
             must oversee the administration of the study drug.

          -  DSM-IV-TR primary diagnosis of autistic disorder confirmation of the diagnosis by a
             trained clinician (eg, psychiatrist, psychologist, social workers, etc) at the time of
             screening, by means of the Autism Diagnostic Interview, Revised (ADI-R).

          -  Screening and Baseline ABC irritability subscale score ≥ 18.

          -  Screening and Baseline CGI-S ≥ 4.

          -  Within 5th to 95th percentile for gender specific Growth Charts from Centers for
             Disease Control (CDC).

          -  No clinically relevant abnormal laboratory values.

          -  No clinically relevant abnormal vital sign values/findings

               1. 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 7 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 (eg,
        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 7 days after the last dose of study
             drug has been taken.

          -  In the judgment of the investigator, the subject is able to swallow the size and
             number of study drug tablets specified per protocol (See Table 4 for study drug tablet
             size).

          -  Able to adhere to protocol-specified meal requirements during dosing.

          -  Have a stable living arrangement for at least 3 months prior to screening.

          -  Non-pharmacologic therapy (eg, behavior modification) must be stable for at least 4
             weeks before screening and consistent throughout the study.

        Exclusion Criteria:

          -  Subjects with profound intellectual disability.

          -  Current diagnosis of bipolar disorder, psychosis, schizophrenia or major depression,
             or childhood disintegrative disorder as confirmed by the MINI-Kid (as appropriate) at
             screening. Confirmed genetic disorders with cognitive and behavioral disturbances are
             also exclusionary.

          -  Clinically significant neurological, metabolic (including type 1 and type 2 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.

          -  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.

          -  If the subject has a history of seizures, the subjects must not currently be taking
             any antiepileptic drugs (AEDs) and be seizure-free for at least 6 months.

          -  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, severe dystonia, or moderate to severe tardive dyskinesia.

          -  Clinically significant alcohol abuse/dependence or drug abuse/dependence based on Mini
             International Neuropsychiatric Interview for children and adolescents (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 4
             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 test results at screening for:

               1. Urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine,
                  opiates, phencyclidine, cannabinoids, methamphetamine, 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).

               2. Pregnancy test (only in female subjects ≥ 11 years old).

          -  Lifetime history of human immunodeficiency virus (HIV) positive or acquired immune
             deficiency syndrome (AIDS), or history of Hepatitis B or C.

          -  Participated in another interventional clinical trial or receiving an investigational
             product within 30 days prior to study drug administration.

          -  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.

          -  Subject has received treatment with antidepressants within 3 days, fluoxetine
             hydrochloride at any time within 21 days, an MAO inhibitor within 21 days of
             randomization or clozapine within 120 days of randomization. Depot neuroleptics must
             be discontinued at least one treatment cycle prior to randomization.

          -  Use of any antipsychotic medication (other than study drug), carbamazepine,
             oxcarbazepine or fluvoxamine, within 3 days prior to randomization.

          -  Females who are pregnant, lactating, or likely to become pregnant during the study.

          -  Donation of whole blood within 60 days prior to randomization.

          -  Has a prolactin concentration greater than or equal to 100 ng/mL at screening.

          -  Subject is considered by the investigator to be at imminent risk of suicide 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.

          -  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.