Multicenter Study of Lumateperone for the Treatment of Bipolar Depression in Pediatric Patients

The study will be conducted in 3 phases:

• Screening Period (up to 2 weeks) during which patient eligibility will be assessed
• Double-blind Treatment Period (6 weeks) during which all patients will be randomized to receive lumateperone or placebo in 1:1 ratio.
• Safety Follow-up Period (1 week) during which all patients will return to the clinic for a safety follow-up (SFU) visit approximately one week after the last dose of study drug.

Inclusion criteria

• Able to provide consent as follows:

• The Legally Authorized Representative (LAR) must provide written, informed consent.
• The patient must provide written assent;
• Male or female patients 10 to 17 years of age, inclusive;
• Have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Text Revision (DSM-5-TR) primary diagnosis of bipolar I or bipolar II disorder with a current MDE without psychosis as confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL);
• Subject has a lifetime history of at least one manic or hypomanic episode.
• Subject's current major depressive episode is ≥ 4 weeks and less than 12 months in duration;
• CDRS-R total score ≥ 45 with ≥ 5 on Item 11 (depressed feelings) at Screening and Baseline;
• Young Mania Rating Scale (YMRS) score ≤ 15 (with YMRS Item 1 [elevated mood] score ≤ 2) at Screening and Baseline.

Exclusion criteria

• Has a primary psychiatric diagnosis other than bipolar I or bipolar II disorder. Exception includes:

• Attention deficit hyperactivity disorder (ADHD). If a subject is taking medications 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.
• Intellectual disability based on Investigator opinion and DSM-5 criteria
• Patient has been hospitalized for a bipolar manic episode within the 30 days prior to randomization;
• Demonstrates a ≥ 25% decrease (improvement) in the CDRS-R total score between Screening and Baseline visits, or the CDRS-R is below 45 at Baseline;
• In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during his/her participation in the study or

• At Screening, the patient scores "yes" on Suicidal Ideation Items 3, 4, or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening or, at Baseline, the patient scores "yes" on Suicidal Ideation Items 3, 4, or 5 since the Screening Visit;
• At Screening, the patient has had 1 or more suicidal attempts within the 2 years prior to Screening; or
• At Screening or Baseline, scores > 3 on Item 13 (suicidal ideation) on the CDRS-R; or
• The patient is considered to be an imminent danger to him/herself or others.