S117. Favorable Long-Term Safety Profile of Lumateperone Iiti-007): Results From a 12 Month Open Label Safety Study for Lumateperone in Patients With Stable Symptoms of Schizophrenia

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

“…A 1-year open-label study assessing the effect of lumateperone treatment taken in the morning vs the evening found a lower incidence of somnolence/sedation (5.8%) with evening administration. This suggests that nightly administration may reduce somnolence and sedation ( Vanover et al ., 2019 ).…”

“…Additionally, there were no notable mean changes in EPS, including akathisia and dyskinesia, on the BARS total, AIMS and SAS clinician-rated scales. The limited EPS and motor adverse effects of lumateperone may arise from the low striatal D 2 receptor occupancy (D 2 RO) of lumateperone at therapeutically relevant doses, with approximately 40% D 2 RO at its recommended therapeutic dose of 42 mg in patients with schizophrenia ( Vanover et al ., 2019 ). This D 2 RO is notably lower than most other antipsychotics which are associated with 65–80% D 2 RO at therapeutically relevant doses, other than clozapine (48–61% occupancy) ( Vanover et al ., 2019 ).…”

“…The limited EPS and motor adverse effects of lumateperone may arise from the low striatal D 2 receptor occupancy (D 2 RO) of lumateperone at therapeutically relevant doses, with approximately 40% D 2 RO at its recommended therapeutic dose of 42 mg in patients with schizophrenia ( Vanover et al ., 2019 ). This D 2 RO is notably lower than most other antipsychotics which are associated with 65–80% D 2 RO at therapeutically relevant doses, other than clozapine (48–61% occupancy) ( Vanover et al ., 2019 ). The MoA at the D 2 receptor as a presynaptic partial agonist and postsynaptic antagonist may contribute to the action of lumateperone at lower D 2 occupancy than other atypical antipsychotics ( Snyder et al ., 2015 ).…”

The role of lumateperone in the treatment of schizophrenia

“…In the second part of this study, 602 patients with schizophrenia were moved from SOC to 42 mg lumateperone once daily for up to 1 year. 48,49,68 The mean change in the Calgary Depression Scale for Schizophrenia score 69 from the baseline was −0.6 ( p = 0.01) and the mean change from SOC baseline in the PANSS total score 63 was −4.0 ( p < 0.001) at day 368. In patients with moderate to severe depression, improvements were more noticeable at baseline.…”

“…Multiple clinical trials conducted by the pharmaceutical company marketing lumateperone have reported beneficial effects without safety issues. 39,[45][46][47][48][49] Key clinical trials for lumateperone for schizophrenia are summarized in Table 1.…”