Intra-Cellular Therapies (ITCI) Study Result summary

Study design and patient population

• Studies 501 and 502 were global, multicenter, randomized, double-blind, placebo-controlled Phase 3 trials evaluating lumateperone 42 mg as adjunctive therapy in adults with MDD who had inadequate response to 1–2 prior antidepressant therapies.

• 480 patients aged 18–65 were randomized 1:1 in Study 502; mean age was 45.6 (lumateperone) and 46.4 (placebo), with about 70% female and majority White (~95%).

• Key inclusion criteria: DSM-5 MDD, MADRS ≥24, CGI-S ≥4, QIDS-SR-16 ≥14, and failure to achieve remission with 1–2 prior antidepressant courses.

• Primary endpoint: mean change in MADRS total score at week 6; key secondary endpoint: mean change in CGI-S at week 6.

Efficacy results

• Lumateperone 42 mg showed a statistically significant and clinically meaningful reduction in MADRS total score at week 6 versus placebo (LS mean difference = -4.5; effect size 0.56; p<0.0001).

• Statistically significant improvement in CGI-S score at week 6 (effect size 0.51; p<0.0001).

• Patient-reported QIDS-SR-16 scores improved significantly with lumateperone (LS mean difference: -2.2 to -7.9, p<0.0001).

• Statistically significant separation from placebo was observed from week 2 and maintained throughout the study.

• Efficacy results were consistent across both pivotal Phase 3 trials (501 and 502), supporting the planned sNDA submission.

Safety and tolerability

• Lumateperone was generally safe and well-tolerated; most adverse events were mild to moderate and resolved during the study.

• Most common adverse events (≥5% and >2x placebo): dizziness, somnolence, dry mouth, nausea, diarrhea, and fatigue.

• One serious adverse event occurred in the lumateperone group, unrelated to the drug.

• No significant metabolic or movement disorder side effects were observed; akathisia rates were similar to placebo.

• Safety profile was consistent with previous lumateperone studies in MDD, bipolar depression, and schizophrenia.