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

A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Lumateperone for the Treatment of Major Depressive Episodes (MDEs) Associated With Bipolar I or Bipolar II Disorder (Bipolar Depression) in Pediatric Patients Aged 10 to 17 Years

This is a multicenter, randomized, double-blind, placebo-controlled study in pediatric patients who are experiencing major depressive episodes (MDEs) associated with a primary diagnosis of bipolar I or bipolar II disorder as confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5).

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:

1. Able to provide consent as follows:

   • The Legally Authorized Representative (LAR) must provide written, informed consent.
   • The patient must provide written assent;

2. Male or female patients 10 to 17 years of age, inclusive;

3. 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);

4. Subject has a lifetime history of at least one manic or hypomanic episode.

5. Subject's current major depressive episode is ≥ 4 weeks and less than 12 months in duration;

6. CDRS-R total score ≥ 45 with ≥ 5 on Item 11 (depressed feelings) at Screening and Baseline;

7. Young Mania Rating Scale (YMRS) score ≤ 15 (with YMRS Item 1 [elevated mood] score ≤ 2) at Screening and Baseline.

Exclusion Criteria:

1. 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.

2. Intellectual disability based on Investigator opinion and DSM-5 criteria

3. Patient has been hospitalized for a bipolar manic episode within the 30 days prior to randomization;

4. 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;

5. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during his/her participation in the study or

   1. 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;
   2. At Screening, the patient has had 1 or more suicidal attempts within the 2 years prior to Screening; or
   3. At Screening or Baseline, scores > 3 on Item 13 (suicidal ideation) on the CDRS-R; or
   4. The patient is considered to be an imminent danger to him/herself or others.