Study of Lumateperone in the Acute Treatment of Patients With Bipolar Mania

The study will be conducted in 3 phases:

• Screening Period (up to 1 week) during which patient eligibility will be assessed.
• Double-blind Treatment Period (3 weeks) during which all eligible patients will be randomized to receive lumateperone 42 mg 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 visit

Inclusion criteria

• Able to provide written informed consent before the initiation of any study specific procedures;
• Male or female inpatient, between the ages of 18 and 75 years, inclusive;
• Meets the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM 5) criteria for bipolar I disorder with a current episode of mania or mania with mixed features with or without psychotic symptoms, as confirmed by a trained and Sponsor-approved rater using the modified Structured Clinical Interview for DSM-5, Clinical Trials Version (SCID-5-CT);
• YMRS total score ≥ 20 and a score of at least 4 on two of the following YMRS items: irritability, speech, content, and disruptive/aggressive behavior at Screening and Baseline;
• Hospitalized voluntarily before Screening or admitted to inpatient unit at Visit 1 with a primary diagnosis of mania but not > 14 days before Screening. Hospital admission must be a result of the current manic episode.

Exclusion criteria

• Has a current primary DSM 5 psychiatric diagnosis other than bipolar disorder. These include:

• Schizophrenia, schizoaffective disorder, or other psychotic disorders;
• Dementia or other cognitive disorders;
• Intellectual disability;
• Moderate or severe substance use disorder (excluding for nicotine);
• Experiencing first manic episode;
• In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during the course of his/her participation in the study or

• At Screening, the patient scores "yes" on Items 4 or 5 in the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening; or
• At Screening, the patient has had 1 or more suicidal attempts within 2 years prior to Screening; or
• At Baseline, the patient scores "yes" on Items 4 or 5 in the Suicidal Ideation section of the C-SSRS since the Screening Visit; or
• At Screening or Baseline, scores ≥ 4 on Item 10 (suicidal thoughts) on the rater administered Montgomery-Åsberg Depression Rating Scale (MADRS); or
• Considered to be an imminent danger to himself/herself or others.