LAUSR

Abstract Introduction Lumateperone (LUMA) is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. An open-label study (Study 303) evaluated the safety and tolerability of LUMA in outpatients with stable schizophrenia who switched from previous antipsychotic (AP) treatment. This post hoc analysis of Study 303 investigated the safety and tolerability of LUMA stratified by previous AP in patients who switched to LUMA treatment for 6 weeks. Methods Adult outpatients (≥18 years) with stable schizophrenia were switched from previous AP to LUMA 42 mg once daily for 6 weeks followed by switching to another approved AP for 2 weeks follow-up. Post hoc analyses were stratified by most common previous AP: risperidone or paliperidone (RIS/PAL); quetiapine (QET); aripiprazole or brexpiprazole (ARI/BRE); olanzapine (OLA). Safety analyses included adverse events (AE), vital signs, and laboratory tests. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impressions-Severity (CGI-S) scale. Results The safety population comprised 301 patients, of which 235 (78.1%) were previously treated with RIS/PAL (n=95), QET (n=60), ARI/BRE (n=43), or OLA (n=37). Rates of treatment-emergent AEs (TEAEs) while on LUMA were similar between previous AP groups (44.2%-55.8%). TEAEs with incidences of ≥5% in any AP group were dry mouth, somnolence, sedation, headache, diarrhea, cough, and insomnia. Most TEAEs were mild or moderate in severity for all groups. Rates of serious TEAEs were low and similar between groups (0%–7.0%). Statistically significant (P<.05) decreases from baseline were observed in the OLA group that switched to LUMA in total cholesterol and low-density lipoprotein cholesterol with significant decreases thereafter on LUMA. Statistically significant decreases in prolactin levels were observed in both the RIS/PAL (P<.0001) and OLA (P<.05) groups. Patients switched from RIS/PAL to LUMA showed significant (P<.05) decreases for body mass index, waist circumference, and weight. At follow-up, 2 weeks after patients switched back from LUMA to another AP, none of the decreases in laboratory parameters or body morphology observed while on LUMA maintained significance. Those switching from QET had significant improvements from baseline at Day 42 in PANSS Total score (mean change from baseline −3.47; 95% confidence interval [CI] −5.27, −1.68; P<.001) and CGI-S Total score (mean change from baseline −0.24; 95% CI, −0.38, −0.10; P<.01). Conclusion In outpatients with stable schizophrenia, LUMA 42 mg treatment was well tolerated in patients switching from a variety of previous APs. Patients switching from RIS/PAL or OLA to LUMA had significant improvements in cardiometabolic and prolactin parameters. These data further support the favorable safety, tolerability, and efficacy of LUMA in patients with schizophrenia. Funding Intra-Cellular Therapies, Inc.