Lumateperone Treatment of Manic Episodes With or Without Mixed Features in Bipolar I Disorder: Results From a Double-Blind, Placebo-Controlled, Randomized, Phase 3 Trial - Digital PLS

Authors: Andrew J. Cutler,¹ Willie R. Earley,² Robert Hayes,² Changzheng Chen,² Hassan Lakkis,² Maxine Chen,² David Brown,³ Michael E. Thase⁴

 

What do the results mean for individuals with Bipolar I disorder? 

In a clinical trial, lumateperone 42 mg was evaluated for the treatment of manic episodes with or without mixed features in adult patients with bipolar I disorder. Results showed a statistically significant and clinically meaningful change in Young Mania Rating Scale (YMRS) total score from baseline, starting at Day 3 and up until Day 22, compared with placebo.

 

What was the purpose of this study?

To understand the efficacy and safety of lumateperone for treatment of manic episodes in adults with bipolar I disorder, including those with mixed features.

 

 

How was the study conducted and what was the design?

The study was a Phase 3, randomized, double-blind, placebo-controlled trial in which patients were assigned 1:1 to receive either lumateperone 42 mg or placebo once daily for 3 weeks followed by a 1-week safety follow-up. Adult hospitalized patients diagnosed with bipolar I disorder according to DSM-5 criteria, who were experiencing a current manic episode, with or without mixed features, that began ≤4 weeks before Visit 1 were included. Patients were required to have a YMRS total score ≥20, with marked symptoms (score ≥4) in at least two key areas (irritability, speech, thought content, or disruptive/aggressive behavior) and a Clinical Global Impression–Severity (CGI-S) score ≥4 at Visits 1 and 2.

 

 

What were the results of the analysis?

There were 177 patients treated with lumateperone and 177 treated with a placebo. The average age of patients was 46.6 years, 58.8% of patients had experienced ≤5 manic episodes in their lifetime, and 15.3% of patients had mixed features. YMRS total scores at baseline indicated that most patients were experiencing severe mania (lumateperone group: 33.2; placebo group: 32.1).

Results showed a statistically significant change in YMRS total score from baseline through to Day 22 compared to placebo with a least square mean difference (LSMD) of -4.8 (p<0.0001) and improvements as early as Day 3.

More patients receiving lumateperone showed significantly greater response (YMRS total score ≥50% decrease; p<.0001) and remission (YMRS total score ≤12; p=.0009) compared with those who received placebo. Statistically significant improvements in CGI-S score were achieved from baseline through to Day 22 compared with placebo, with a LSMD -0.5 (p<0.0001).

 

 

Less than 2% of patients in the lumateperone group discontinued treatment due to adverse events.

 

 

References

¹Department of Psychiatry, SUNY Upstate Medical University, Lakewood Ranch, FL, USA; ²Johnson & Johnson, Titusville, NJ, USA; ³Community Clinical Research, Inc., Austin, TX, USA; ⁴Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

 

Presented at Psych Congress, September 15–19, 2026; New Orleans, Louisiana

 

Scan the QR Code for the full poster

 

This material is distributed for scientific purposes by Johnson & Johnson Innovative Medicine and is not for promotional use.

 

AI was used in the preparation of this summary