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

A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Lumateperone in the Acute Treatment of Patients With Manic Episodes or Manic Episodes With Mixed Features Associated With Bipolar I Disorder (Bipolar Mania)

This is a multicenter, randomized, double-blind, placebo-controlled, study in the acute treatment of patients with a diagnosis of bipolar I disorder with manic episodes or manic episodes with mixed features (bipolar mania), with or without psychotic symptoms, 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 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:

1. Able to provide written informed consent before the initiation of any study specific procedures;
2. Male or female inpatient, between the ages of 18 and 75 years, inclusive;
3. 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);
4. 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;
5. 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:

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

   1. Schizophrenia, schizoaffective disorder, or other psychotic disorders;
   2. Dementia or other cognitive disorders;
   3. Intellectual disability;
   4. Moderate or severe substance use disorder (excluding for nicotine);

2. Experiencing first manic episode;

3. 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

   1. 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
   2. At Screening, the patient has had 1 or more suicidal attempts within 2 years prior to Screening; or
   3. 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
   4. At Screening or Baseline, scores ≥ 4 on Item 10 (suicidal thoughts) on the rater administered Montgomery-Åsberg Depression Rating Scale (MADRS); or
   5. Considered to be an imminent danger to himself/herself or others.