Lumateperone Monotherapy for the Treatment of Bipolar Depression Conducted Globally

• Lumateperone (Drug), also known as ITI-007: Lumateperone 42 mg (ITI-007 60 mg tosylate)
• Placebo (Other): Placebo

Primary outcomes

• Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score [Baseline to Day 43]: The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.

Secondary outcomes

• Change From Baseline in Clinical Global Impression Scale, Bipolar Version (CGI-BP-S) Total Score [Baseline to Day 43]: The Clinical Global Impression Scale, Bipolar version (CGI-BP-S) total score is a clinician-rated scale that measures the patient's current illness state on a 3 to 21 point scale where a higher score is associated with greater illness severity.. Each domain (depression, mania, and overall illness) is rated from 1 (not ill at all) to 7 (among the most extremely ill) and the 3 scores are added to obtain the total score.
• Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Percent Score [Baseline to Day 43]: The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 14 item patient self-reported questionnaire that assesses how satisfied a patient is, using a 5-point scale from 1-very poor to 5-very good.

Sex: All, ages: 18 Years to 75 Years

Major Inclusion Criteria:

* male or female subjects of any race, ages 18-75 inclusive, with a clinical diagnosis of Bipolar I or Bipolar II disorder
* experiencing a current major depressive episode
* able to provide written informed consent

Major Exclusion Criteria:

* any female subject who is pregnant or breast-feeding
* any subject judged to be medically inappropriate for study participation

Participant flow

Outcome results

• Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score (Primary), Least squares mean, score on a scale: Lumateperone -16.70 +/- 0.693; Placebo -12.12 +/- 0.677 (p <0.0001)
• Change From Baseline in Clinical Global Impression Scale, Bipolar Version (CGI-BP-S) Total Score (Secondary), Least squares mean, score on a scale: Lumateperone -3.48 +/- 0.170; Placebo -2.54 +/- 0.167 (p <0.0001)
• Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Percent Score (Secondary), Least squares mean, Percent Score: Lumateperone 19.4 +/- 1.49; Placebo 14.9 +/- 1.45 (p 0.005)

Adverse events

Time frame: From signing ICF until end of study procedures (~10 weeks), including 6 weeks of double-blind treatment.

Serious adverse events by term

Other adverse events by term

• Results publication: Durgam S, Lakkis H, Kozauer SG, Chen C, McIntyre RS. Efficacy of Lumateperone in depression associated with bipolar II disorder: a pooled analysis of late-phase clinical trials. CNS Spectr. 2025 Sep 29;30(1):e80. doi: 10.1017/S1092852925100564. PMID 41017591
• Results publication: McIntyre RS, Durgam S, Huo J, Kozauer SG, Stahl SM. The Efficacy of Lumateperone in Patients With Bipolar Depression With Mixed Features. J Clin Psychiatry. 2023 Apr 24;84(3):22m14739. doi: 10.4088/JCP.22m14739. PMID 37103915
• Results publication: Calabrese JR, Durgam S, Satlin A, Vanover KE, Davis RE, Chen R, Kozauer SG, Mates S, Sachs GS. Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial. Am J Psychiatry. 2021 Dec;178(12):1098-1106. doi: 10.1176/appi.ajp.2021.20091339. Epub 2021 Sep 23. PMID 34551584

• Study Protocol (PDF, 2018-11-05)
• Statistical Analysis Plan (PDF, 2019-06-12)

• Susan Kozauer, MD, Study director, Intra-Cellular Therapies, Inc.