Results From a 12-Month Open-Label Safety Study of Lumateperone (ITI-007) in Patients With Stable Symptoms of Schizophrenia

Introduction: Lumateperone (ITI-007) is in development for the treatment of schizophrenia and bipolar depression. Lumateperone has a unique mechanism of action that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. In 2 placebo-controlled trials in patients with acute schizophrenia, lumateperone 42mg improved schizophrenia symptoms with a safety profile similar to placebo. This open-label study evaluated the long-term safety and efficacy of lumateperone 42mg.

Methods: Patients with schizophrenia were treated up to 1 year with lumateperone 42mg. Safety assessments included treatment-emergent adverse events (TEAEs), body weight, laboratory parameters, and extrapyramidal symptoms (EPS). Efficacy analyses included changes in Positive and Negative Syndrome Scale (PANSS) Total score and the Calgary Depression Scale for Schizophrenia (CDSS).

Results: In this interim analysis, 602 patients received ≥1 dose of lumateperone 42mg; 107 patients completed 1 year of treatment. TEAEs occurring in ≥5% of patients were weight decrease, dry mouth, headache, and diarrhea; most TEAEs were mild or moderate in intensity. Most metabolic parameters, mean prolactin levels, mean body weight, and BMI decreased from SOC baseline. Based on TEAE reporting and EPS scales, lumateperone was associated with minimal EPS risk. Lumateperone was associated with significant reductions in PANSS Total score from baseline. In patients with moderate-to-severe depression symptoms at baseline (CDSS>5), mean CDSS scores decreased from 7.4 (baseline) to 3.1 (Day 300).

Conclusion: In long-term treatment, lumateperone was associated with minimal metabolic, EPS, and cardiovascular safety issues relative to current SOC therapy. Lumateperone improved schizophrenia symptoms with continued long-term treatment. This interim analysis extends results from placebo-controlled studies.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.