New data from a Phase 3 clinical trial indicates that lumateperone (CAPLYTA) 42 mg significantly delays relapse in patients with schizophrenia compared to placebo. The multi-center, multi-national, randomized, double-blind, placebo-controlled trial (Study 304), announced by Intra-Cellular Therapies, offers promising results for the maintenance treatment of schizophrenia.
Lumateperone, an oral, once-daily atypical antipsychotic, is already approved for the treatment of schizophrenia and depressive episodes associated with bipolar disorder. Its mechanism of action is believed to involve antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.
Study 304: Design and Results
The 47-week trial included an 18-week open-label phase where patients with schizophrenia received lumateperone 42 mg daily. Those who met stabilization criteria were then randomized to either lumateperone 42 mg (n = 114) or placebo (n = 114) for up to 26 weeks or until relapse. The primary endpoint was time to first symptom relapse, with time to all-cause discontinuation as the secondary endpoint.
The results demonstrated a significantly longer time to relapse in the lumateperone group compared to placebo (P = .0002). Specifically, 18 relapses (16.4%) occurred in the lumateperone group, while 44 relapses (38.6%) occurred in the placebo group. This translates to a 63% reduction in the risk of relapse with lumateperone (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.22 – 0.65).
Safety and Tolerability
Lumateperone was generally safe and well-tolerated. The most common adverse event during the double-blind phase was headache, reported in ≥ 5% of participants and at twice the rate of placebo. Other previously observed adverse events include somnolence/sedation, dizziness, nausea, and dry mouth.
Clinical Implications
Relapse is a significant concern in schizophrenia, with studies indicating that up to 81.9% of individuals experiencing a relapse within 5 years of diagnosis. Schizophrenia relapse can lead to increased symptom severity, medication non-adherence, job or legal issues, self-harm, and hospitalization. The results of Study 304 suggest that lumateperone can play a crucial role in preventing relapse and improving long-term outcomes for patients with schizophrenia.
"The control of symptoms and the prevention of relapses is critical to improving long-term patient outcomes," said Suresh Durgam, MD, executive vice president and chief medical officer of Intra-Cellular Therapies. "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."
