Long-term safety and tolerability of lumateperone 42 mg in patients with stable symptoms of schizophrenia: Results from a 1-year open-label study

BACKGROUND: Antipsychotics with a long-term favorable tolerability profile are needed to improve outcomes in patients with schizophrenia. A 1-year, open-label, Phase 3 study investigated long-term safety and efficacy of lumateperone 42 mg (a simultaneous modulator of serotonin, dopamine, and glutamate) in patients with stable schizophrenia. METHODS: Adult outpatients (≥18 years) with DSM-5-defined schizophrenia with stable pathology received lumateperone 42 mg orally once daily for 368 days. The primary endpoint was safety, assessed by adverse events (AEs) and changes in extrapyramidal symptoms (EPS), cardiometabolic and prolactin parameters, and vital signs. Secondary endpoints included change in Positive and Negative Syndrome Scale (PANSS) Total score and Calgary Depression Scale for Schizophrenia (CDSS). RESULTS: Of 602 patients treated with lumateperone 42 mg, 229 (38.0%) completed 1-year treatment. Treatment-emergent AEs (TEAEs) occurred in 390 patients (64.8%); the most common TEAEs (≥5%) were weight decreased (10.1%), diarrhea (7.6%), dry mouth (7.6%), and headache (7.3%). There were no notable changes in EPS-related scales. Significant improvements occurred for total and low-density lipoprotein cholesterol (P < .001), prolactin (P < .05), and triglycerides (P < .05) at Day 368. Weight, body mass index, and waist circumference significantly decreased throughout the study to Day 368 (P < .001). Lumateperone significantly improved PANSS Total score (mean change = -4.2; 95% CI = -5.6 to -2.8; effect size [ES] = -0.39; P < .001) and CDSS Total score (mean change = -0.6; 95% CI = -0.99 to -0.23; ES = -0.21; P < .01) at Day 368. CONCLUSION: Lumateperone 42 mg demonstrated a favorable safety profile with improvements in cardiometabolic and prolactin parameters and a low EPS risk and maintenance of stable symptoms of schizophrenia over 1-year treatment.