SUMMARY

• Durgam et al (2025)¹ conducted a phase 3, randomized, multicenter, multinational, double-blind, placebo-controlled, withdrawal study (study 304) to evaluate the efficacy and safety of CAPLYTA 42 mg to prevent relapses in adult patients with schizophrenia.
  • During the double-blind treatment phase, patients receiving CAPLYTA had a significantly longer time to relapse compared to those receiving placebo, with a hazard ratio (HR) of 0.37 (95% confidence interval [CI]: 0.22, 0.65; P=0.0002). The number of relapses reported in the CAPLYTA group was 18 (16.4%) vs 44 (38.6%) in the placebo group.
  • During the double-blind treatment phase, CAPLYTA 42 mg also showed a significant delay in time to all-cause discontinuation (including relapse) vs placebo (HR=0.49; 95% CI: 0.32, 0.75; P=0.0007).
  • The most commonly reported (≥5% of the CAPLYTA group and at more than twice the rate of placebo in the double-blind treatment population) treatment-emergent adverse event (TEAE) was headache in both the open-label (OL) (CAPLYTA, 13.2%) and double-blind treatment phases (CAPLYTA, 8.2%; placebo, 3.5%).

PRODUCT LABELING

CAPLYTA is an atypical antipsychotic indicated for: treatment of schizophrenia in adults; treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate; and adjunctive therapy with antidepressants for the treatment of major depressive disorder (MDD) in adults.²

CLINICAL DATA

Durgam et al (2025)¹ conducted a phase 3, randomized, multicenter, multinational, double-blind, placebo-controlled, withdrawal study (study 304) to evaluate the efficacy and safety of CAPLYTA 42 mg to prevent relapses in adult patients with schizophrenia. The study consisted of: an 18-week OL treatment phase where patients experiencing a current psychotic episode (n=592) received CAPLYTA 42 mg once daily; and a double-blind treatment phase where patients who met stabilization criteria during the OL treatment phase were randomized (1:1) to continue on CAPLYTA 42 mg (n=110) or switch to placebo (n=114) for 26 weeks or until relapse. The primary endpoint was the time to first symptom relapse during the double-blind treatment phase. Relapse was defined as meeting ≥1 of the following criteria:

• Psychiatric hospitalization or increased psychiatric care
• Increase in Positive and Negative Syndrome Scale (PANSS) Total score by ≥30% for patients with PANSS Total score ≥50 at randomization, or a ≥10-point increase in PANSS Total score for patients who scored <50 at randomization
• Increase of 2 or more points in Clinical Global Impression-Severity (CGI-S) score
• Self-injury or aggressive/violent behavior
• Suicidal or homicidal ideation
• PANSS item scores >4 on 1 or more of the following PANSS items: delusions, conceptual disorganization, hallucinatory behavior, suspiciousness, hostility, uncooperativeness, or poor impulse control

Efficacy

• During the double-blind treatment phase, patients receiving CAPLYTA had a significantly longer time to relapse compared to those receiving placebo, with an HR of 0.37 (95% CI: 0.22, 0.65; P=0.0002). The number of relapses reported in the CAPLYTA group was 18 (16.4%) vs 44 (38.6%) in the placebo group.
• During the double-blind treatment phase, CAPLYTA 42 mg also showed a significant delay in time to all-cause discontinuation (including relapse) vs placebo (HR=0.49; 95% CI: 0.32, 0.75; P=0.0007).

Safety

• TEAEs were reported in 52% of patients in the OL treatment phase, and 33.6% of patients in the CAPLYTA group vs 30.7% of patients in the placebo group during the double-blind treatment phase.
• The most commonly reported (≥5% of the CAPLYTA group and at more than twice the rate of placebo in the double-blind treatment population) TEAE was headache in both the OL (CAPLYTA, 13.2%) and double-blind treatment phases (CAPLYTA, 8.2%; placebo, 3.5%).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 10 October 2025.