S44. LUMATEPERONE (ITI-007) FOR THE TREATMENT OF SCHIZOPHRENIA: PLACEBO-CONTROLLED CLINICAL TRIALS AND AN OPEN-LABEL SAFETY SWITCHING STUDY

• Published in: Schizophrenia bulletin 2018-04, Vol.44 (suppl_1), p.S341-S341
• Main Authors: Vanover, Kimberly, Dmitrienko, Alex, Glass, Steven, Kozauer, Susan, Saillard, Jelena, Weingart, Michal, Satlin, Andrew, Mates, Sharon, Correll, Christoph, Davis, Robert
• Format: Article
• Language: English
• Subjects: Abstracts
• ISSN: 0586-7614; 1745-1701
• DOI: 10.1093/schbul/sby018.831

Abstract Background Lumateperone (ITI-007) is a first-in-class investigational agent in development for the treatment of schizophrenia. Acting synergistically through serotonergic, dopaminergic and glutamatergic systems, lumateperone represents a new approach to the treatment of schizophrenia and other neuropsychiatric disorders. Lumateperone is a potent antagonist at 5-HT2A receptors and exhibits serotonin reuptake inhibition. Lumateperone also binds to dopamine D1 and D2 receptors acting as a mesolimbic/mesocortical dopamine phosphoprotein modulator (DPPM) with pre-synaptic partial agonism and post-synaptic antagonism at D2 receptors and as an indirect glutamatergic (GluN2B) phosphoprotein modulator with D1-dependent enhancement of both NMDA and AMPA currents via the mTOR protein pathway. Methods Lumateperone was evaluated in 3 controlled clinical trials to evaluate efficacy in patients with acute schizophrenia. In Study ITI-007-005, 335 patients were randomized equally across 4 treatment arms: one of two doses of lumateperone, risperidone (active control) or placebo QAM for 4 weeks. In Study ITI-007-301, 450 patients were randomized equally across 3 treatment arms: one of two doses of lumateperone or placebo QAM for 4 weeks. In Study ITI-007-302, 696 patients were randomized equally across 4 treatment arms: one of two doses of lumateperone, risperidone (active control) or placebo QAM for 6 weeks. In all 3 studies, the primary endpoint was change from baseline on the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo. Also, a 6-week open-label safety switching study was conducted. In this ITI-007-303 study 302 patients with stable schizophrenia were switched from standard-of-care (SOC) antipsychotics and treated for 6 weeks with lumateperone QPM outpatient and then switched back to SOC for 2 weeks. Results Two of the 3 randomized studies were positive. In Studies ITI-007-005 and ITI-007-301, lumateperone (60 mg ITI-007, equivalent to 42 mg active base) met the primary endpoint with statistically significant superior efficacy over placebo at Day 28 as measured by the PANSS total score (Study ITI-007-005 p=0.017; Study ITI-007-301 p=0.022). In Study ITI-007-302, neither dose of lumateperone separated from placebo on the primary endpoint in the intent-to-treat population; a high placebo response was observed in this study. Across all 3 efficacy trials, lumateperone improved symptoms of schizophrenia with the same trajectory and sam