A recent Phase 3 trial, Study 304, has revealed that lumateperone (Caplyta; Intra-Cellular Therapies), a second-generation antipsychotic, is effective in preventing relapse in adult patients with schizophrenia. The multicenter, randomized, double-blind, placebo-controlled trial offers hope for individuals who struggle with the burden of relapses and have not responded well to other medications.
The study, lasting 47 weeks, included an 18-week open-label phase where patients received lumateperone 42 mg daily. Those who met stabilization criteria then entered a double-blind treatment phase, randomized to either continue lumateperone 42 mg or switch to placebo for up to 26 weeks or until relapse.
The primary endpoint, time to relapse during the double-blind treatment phase, was significantly longer in the lumateperone group compared to the placebo group. Specifically, only 18 patients (16.4%) in the lumateperone group experienced a relapse, compared to 44 patients (38.6%) in the placebo group. This translates to a 63% reduction in the risk of relapse with lumateperone (HR: 0.37; 95% CI, 0.22-0.65).
Key Secondary Endpoint Met
Lumateperone also met a key secondary endpoint: time to all-cause discontinuation during the double-blind phase. The treatment was generally well-tolerated, with headache being the most commonly reported adverse event in the double-blind phase, observed at a rate greater than or equal to 5% and twice the rate of placebo.
Expert Commentary
Suresh Durgam, MD, Executive Vice President and Chief Medical Officer of Intra-Cellular Therapies, stated, "We are very pleased that the results from Study 304, a randomized withdrawal trial, demonstrated efficacy along with favorable safety and tolerability which support the benefit of continued long-term treatment with lumateperone."
Durgam emphasized the importance of relapse prevention in schizophrenia management: "Schizophrenia is a chronic, serious mental illness characterized by the occurrence of acute psychotic episodes that cumulatively worsen disease prognosis. The control of symptoms and the prevention of relapses is critical to improving long-term patient outcomes."
Implications for Treatment
These findings suggest that lumateperone could be a valuable option for patients who have not responded well to other second-generation antipsychotics. However, further clinical trials are needed to fully evaluate its role in this context. Pharmacists should be aware of potential adverse reactions and carefully consider which patients may benefit most from lumateperone, keeping in mind contraindications for individuals with known hypersensitivity to the drug or its components.
