Lumateperone for the Prevention of Relapse in Patients with Schizophrenia:" Results from a double-blind, placebo-controlled, randomized withdrawal, phase 3 trial
Abstract: Background: Lumateperone is an FDA-approved antipsychotic for treating schizophrenia and bipolar depression. This Phase 3, multicenter, multinational, double-blind, placebo-controlled, randomized withdrawal trial (Study 304, NCT04959032) investigated the efficacy and safety of lumateperone 42mg for relapse prevention in adults with schizophrenia.
Methods: Eligible adults had DSM-5 diagnosed schizophrenia for ≥1 year and Positive and Negative Syndrome Scale Total score 70-120. Patients received open-label lumateperone 42mg for 18 weeks (6-week run-in phase, 12-week stabilization phase). Stable patients were randomized 1:1 to double-blind treatment with lumateperone 42 mg or placebo for 26 weeks or until relapse. Primary and key secondary endpoints were time to first symptom relapse and time to all-cause discontinuation, respectively, during double-blind treatment. Safety was assessed.
Results: Of 592 patients treated with lumateperone 42mg in the open-label run-in phase, 228 patients meeting stabilization criteria were randomized to double-blind treatment (lumateperone, n=114; placebo, n=114). Lumateperone met the primary endpoint, significantly delaying time to relapse vs placebo (hazard ratio=0.37; 95%CI, 0.22-0.65; P=.0002). Fewer relapses occurred with lumateperone (n=18 [16.4%]) than placebo (n=44 [38.6%]) with a number needed to treat of 5. Lumateperone also significantly delayed time to all-cause discontinuation vs placebo (P=.0007). Lumateperone was generally safe and well tolerated. Headache was the most common treatment-emergent adverse event (≥5%; or ≥5% with lumateperone and >2x placebo) during the open-label phase (lumateperone, n=78 [13.2%]) and double-blind treatment phase (lumateperone, n=9 [8.2%]; placebo, n=4 [3.5%]).
Conclusion: Lumateperone 42mg was effective, safe, and well tolerated as maintenance treatment supporting its long-term use in adults with schizophrenia.
