Cardiometabolic Safety of Lumateperone (ITI-007): Post Hoc Analyses of Short-Term Randomized Trials and an Open-Label Long-Term Study

Background: Antipsychotic treatment of schizophrenia is often associated with increased rates of metabolic syndrome (MetSy), as defined by criteria for waist circumference, triglycerides, high density lipoprotein cholesterol, blood pressure, and fasting glucose. Lumateperone (lumateperone tosylate, ITI-007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia. This post hoc analysis evaluated MetSy in 2 placebo-controlled studies and an open-label 1-year trial of lumateperone in schizophrenia.

Methods: Incidence and shifts in MetSy were analyzed in data pooled from 2 short-term placebo- and active-controlled (risperidone 4mg) studies of lumateperone 42mg. Data from an open-label trial evaluated MetSy in patients switched from prior antipsychotic (PA) treatment to lumateperone 42mg.

Results: In short-term studies, MetSy rates were similar between groups at baseline (16% lumateperone, 19% risperidone). At the end of treatment (EOT), MetSy was less common with lumateperone than risperidone (13% vs 25%). More lumateperone patients (46%) compared with risperidone (25%) improved from having MetSy at baseline to no longer having MetSy EOT. In the long-term study, 33% of patients had MetSy at PA baseline. Of patients with MetSy at baseline, 36% improved to no longer meeting criteria at EOT. Fewer than half that percentage shifted from not meeting MetSy criteria to having MetSy (15%).

Conclusion: In this post hoc analysis, lumateperone patients had reduced rates of MetSy compared with risperidone and had reduction in the risk of MetSy when switched from a PA. These results suggest that lumateperone 42mg has a favorable metabolic profile.