Safety and tolerability of lumateperone for the treatment of schizophrenia: a pooled analysis of late-phase placebo- and active-controlled clinical trials

Abstract

Lumateperone, an antipsychotic that is US Food and Drug Administration-approved for the treatment of schizophrenia, has a novel mechanism of action that may confer beneficial effects with improved tolerability. This pooled analysis of three randomized, double-blind, placebo-controlled trials was conducted to evaluate the safety and tolerability of lumateperone 42 mg. The pooled population comprised 1073 patients with an acute exacerbation of schizophrenia randomized to placebo (n = 412), lumateperone 42 mg (n = 406) or risperidone 4 mg (n = 255). Treatment-emergent adverse events (TEAEs) were predominantly mild and rates of discontinuation due to TEAEs with lumateperone 42 mg (0.5%) were similar to placebo (0.5%) and lower than risperidone (4.7%). The only TEAEs that occurred at a rate of ≥5% and twice placebo for lumateperone were somnolence/sedation and dry mouth. Mean change from baseline in metabolic parameters and prolactin were similar to or reduced in lumateperone 42 mg relative to placebo-treated patients and were smaller than risperidone. Mean change in weight and rates of extrapyramidal symptoms-related TEAEs were similar for lumateperone 42 mg and placebo-treated patients and less than for risperidone-treated patients. This pooled analysis demonstrates the safety and favorable tolerability profile of lumateperone 42 mg.

Fig. 1

Patient disposition. TEAE, treatment-emergent adverse events.

Fig. 2

Least-squares mean difference of lumateperone vs. risperidone for mean change in key safety parameters. ***P <  0.001 LSMD for lumateperone vs. risperidone from an ANCOVA analysis of least-squares mean change from baseline to last on-treatment value. ANCOVA, analysis of covariance; CI, confidence interval; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LSMD, least-squares mean difference.