Caplyta Reduced Bipolar Mania Symptoms in Phase 3 Trial

Lumateperone (Caplyta, Johnson & Johnson) significantly reduced manic symptoms compared with placebo in adults with bipolar I disorder, according to topline phase 3 results announced by Johnson & Johnson. Improvement was observed by day 3 and sustained through week 3. The findings were presented at the 2026 Psych Congress Annual Meeting.

Study 451 (NCT06462586) was a randomized, double-blind, placebo-controlled trial evaluating once-daily lumateperone 42mg for 3 weeks in adults experiencing manic episodes, with or without mixed features, associated with bipolar I disorder. The primary endpoint was change in Young Mania Rating Scale (YMRS) total score at week 3. Change in Clinical Global Impression–Severity (CGI-S) score was a key secondary endpoint.

At week 3, lumateperone produced a 4.8-point greater reduction in YMRS total score than placebo (effect size, −0.69; P<0.0001). A clinical response, defined as a reduction of at least 50% in YMRS total score, occurred in 45.8% of patients receiving lumateperone and 20.9% receiving placebo. CGI-S scores also favored lumateperone (least-squares mean difference, −0.5; P<0.0001).

Johnson & Johnson reported low discontinuation rates and said the safety findings were consistent with the drug’s established profile. The most common treatment-related adverse events occurring in at least 5% of lumateperone-treated patients and at least twice as often as with placebo were dry mouth (7.9% vs 3.4%) and nausea (7.9% vs 2.3%). Approved labeling includes boxed warnings concerning increased mortality in older adults with dementia-related psychosis and suicidal thoughts and behaviors in people aged 24 years or younger when the drug is used with antidepressants.

Caplyta is not approved for manic episodes associated with bipolar I disorder. Johnson & Johnson said a second pivotal phase 3 trial, Study 452, has been completed and data analysis is underway. The current findings are topline results reported by the company from a conference presentation.

Source: Johnson & Johnson. CAPLYTA (lumateperone) shows significant and rapid improvement in bipolar mania in pivotal phase 3 study. Press release. Johnson & Johnson; September 21, 2026. Accessed September 23, 2026.