New Phase 3 Study Results on Lumateperone, An Adjunctive Therapy to Antidepressants


Lumateperone 42 mg achieved statistically significant and clinically meaningful results in both the primary and the key secondary endpoints of a new phase 3 study.



Positive topline results from study 501 showed that lumateperone (Caplyta) 42 mg was effective as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD).1

Investigators in study 501 found that lumateperone 42 mg, when given once daily as adjunctive therapy to antidepressants, met the primary endpoint by demonstrating a statistically significant and clinically meaningful reduction in the MADRS total score when compared with placebo at week 6. They randomized 485 patients with MDD to lumateperone 42 mg plus antidepressant or placebo plus antidepressant (1:1) in order to evaluate the efficacy and safety of lumateperone as an adjunct to antidepressants. The baseline MADRS total score was 30.4 for lumateperone 42 mg and 30.0 for placebo. In the modified intent-to-treat (mITT) study population, the least squares (LS) mean reduction from baseline for lumateperone 42 mg was 14.7 points, versus 9.8 points for placebo (LS mean difference = -4.9 points; p<0.0001; ES= 0.61).

“The positive phase 3 results in MDD represent a significant step towards our goal of further establishing Caplyta as a first-choice treatment across mood disorders,” said Sharon Mates, PhD, chairman and CEO of Intra-Cellular Therapies. “We believe that these robust efficacy results coupled with its favorable safety and tolerability profile and convenient dosing make Caplyta a compelling option as an adjunctive treatment for MDD, if approved. At Intra-Cellular Therapies, we are committed to bringing improved treatment options to patients with major neuropsychiatric conditions through our efforts to expand Caplyta’s label and advance our pipeline.”

Lumateperone 42 mg also met the key secondary endpoint in the study by demonstrating a statistically significant and clinically meaningful reduction in the CGI-S score when compared with placebo at week 6 (p<0.0001; ES= 0.67). This statistically significant efficacy was seen early at the first time point tested (week 1) and maintained throughout the study in both the primary and the key secondary endpoints.

Additionally, lumateperone 42 mg improved patient-reported depressive symptoms as measured by the Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR-16) (p<0.0001). The QIDS-SR-16 is a 16-item patient-rated scale of symptom severity in depression, which assesses 9 key symptoms of depression: insomnia/hypersomnia, low mood, appetite/weight changes, impaired self-perception, concentration difficulties, loss of interest/pleasure, suicidal ideation, psychomotor agitation, and fatigue.

Lumateperone was generally safe and well-tolerated, with the most commonly reported adverse events were dry mouth (10.8%), fatigue (9.5%), and tremor (5.0%). These were observed at a rate greater than or equal to 5% and at least twice the rate of placebo in the total population, but they were mostly mild to moderate and resolved within a short period of time. Similar adverse events were seen in prior studies of lumateperone as a treatment for bipolar depression and schizophrenia.2

“MDD is a highly prevalent condition and there is a need for efficacious treatments with favorable safety and tolerability profiles given the majority of patients do not benefit from their initial therapy or suffer from side effects associated with existing therapies,” said Suresh Durgam, executive vice president and chief medical officer of Intra-Cellular Therapies. “In this phase 3 study, lumateperone demonstrated a robust effect as an adjunctive treatment to antidepressants in patients with MDD who had inadequate response to antidepressant therapy. This study contributes to the growing body of evidence of lumateperone’s efficacy and safety across mood disorders.”

Topline results from a second phase 3 study, study 502, are anticipated late in the second quarter of this year.


1. Intra-Cellular Therapies announces positive phase 3 topline results from study 501 evaluating lumateperone as adjunctive therapy in patients with major depressive disorder. Intra-Cellular Therapies. News release. April 16, 2024.

2. Kuntz L. Positive results for lumateperone in patients with mixed features in major depressive disorder, bipolar depression. Psychiatric Times. March 29, 2023.

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