Lurasidone Pediatric Bipolar Study
Condition: Bipolar I Depression
MeSH terms: Depression; Depressive Disorder
Intervention: Lurasidone; Placebo
Intervention description: Lurasidone flexibly dosed 20-80 mg once daily; Placebo Comparator 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: 350.0
Sex: All
Minimum age: 10 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Lurasidone, Latuda, Bipolar Depression

Summary:

      A study to evaluate efficacy and safety of flexibly dosed Lurasidone in children and
      adolescents with bipolar I depression
    

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. If
             emancipated, subjects must provide written informed consent. In accordance with
             Institutional Review Board (IRB) requirements, the subject will complete an informed
             assent prior to study participation.

               -  Male or female subjects 10 to 17 years of age, inclusive with bipolar I disorder,
                  most recent episode depressed, with or without rapid cycling disease course (≥ 4
                  episodes of mood disturbance but < 8 episodes in the previous 12 months) and
                  without psychotic features (diagnosed by DSM-V criteria, and confirmation of the
                  bipolar I disorder 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]). Note: The current episode of major depression
                  associated with bipolar I disorder must be confirmed by the investigator and
                  noted in the source records.

               -  Subject has a lifetime history of at least one manic episode. A reliable
                  informant (eg, family member or caregiver) or medical records must be able to
                  confirm this history.

               -  Subject's current major depressive episode is ≥ 4 weeks and less than 12 months
                  in duration.

               -  CDRS-R score ≥ 45 at screening and Baseline.

               -  YMRS score ≤ 15 (with YMRS Item 1 [elevated mood] score ≤ 2) at screening and
                  Baseline.

               -  Within 3rd to 97th percentile for gender specific BMI-for-age growth charts from
                  the World Health Organization (WHO) growth charts

               -  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 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

               -  Willing and able to adhere to protocol-specified meal requirements during dosing.

               -  Subjects may have a lifetime diagnosis of ADHD. If a subject is taking
                  psychostimulants for ADHD, they must have been on a stable treatment regimen of
                  these medication(s) for 30 days prior to screening and the treatment regimen is
                  expected to remain stable throughout the study. This must be confirmed by the
                  investigator and noted in the source records.

        Exclusion Criteria:

          -  Has an Axis I or Axis II (DSM-IV or any DSM-5) diagnosis other than bipolar I disorder
             that has been the primary focus of treatment within 3 months of screening.

          -  Subject has been hospitalized for a bipolar manic or mixed episode within the 30 days
             prior to randomization.

          -  Has a history or current diagnosis of intellectual disability, autism spectrum
             disorder, 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.

          -  CDRS-R total score > 85 at screening or Baseline

          -  Demonstrates a decrease (improvement) of ≥ 25% in the CDRS-R adjusted total score
             between Screening and Baseline visits, or the CDRS-R is below 45 at 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 prior adequate trials (ie,
             adequate dose and duration) of an antipsychotic agent within the current episode of
             depression, or subject has a history of non-response to an adequate (6-week) trial of
             three or more antidepressants (with or without mood stabilizers) during the current
             episode.

          -  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.

          -  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.

          -  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 substance abuse disorder (with the exception of caffeine or
             tobacco) based on DSM-5 criteria within the last 6 months prior to screening.

          -  Positive test results at screening or Baseline for:

               1. Urine drugs of abuse (including amphetamines/methamphetamines, barbiturates,
                  benzodiazepines, cocaine, opioids, phencyclidine, and cannabinoids). A positive
                  test for amphetamines/methamphetamines, barbiturates, opioids, or benzodiazepines
                  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), 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 screening.

          -  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, atomoxetine or alpha 2 agonists (eg,
             guanfacine) 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 all psychotropic medications prior to randomization with the exception of those
             medications explicitly permitted within 3 days prior to randomization (7 days prior to
             randomization for aripiprazole).

          -  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 or has a score of 7 on item 13, Suicidal Ideation, on the CDRS-R.

          -  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.

          -  Subject with newly diagnosed Type 2 diabetes during screening or subject is on
             injectable medication for the treatment of Type 2 diabetes. 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.

          -  The use of concomitant medications that are potent inducers or inhibitors of the
             cytochrome P450 (CYP) 3A4 enzyme system during the trial (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).