Efficacy and safety of lurasidone 80 mg/day and 160 mg/day in the treatment of schizophrenia: A randomized, double-blind, placebo- and active-controlled trial

Objective: This study was designed to evaluate the short-term efficacy and safety of once-daily lurasidone (80 mg/day and 160 mg/day) in the treatment of an acute exacerbation of schizophrenia. Methods: Participants, who were recently admitted inpatients with schizophrenia with an acute exacerbation of psychotic symptoms, were randomly assigned to 6 weeks of fixed-dose, double-blind treatment with lurasidone 80 mg (n = 125), lurasidone 160 mg (n = 121), quetiapine XR 600 mg (QXR-600 mg; n = 119; active control included to test for assay sensitivity), or placebo (n = 121), all dosed once daily in the evening. Efficacy was evaluated using a mixed-model repeated-measures analysis of the change from Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total score (the primary efficacy measure) and Clinical Global Impressions severity (CGI-S) score (the key secondary efficacy measure). Results: Treatment with both doses of lurasidone or with QXR-600 mg was associated with significantly greater improvement at Week 6 on PANSS total score, PANSS positive and negative subscale scores, and CGI-S score compared with placebo. The endpoint responder rate (>= 20% improvement in PANSS total score) was higher in subjects treated with lurasidone 80 mg (65%; p<0.001), lurasidone 160 mg (79%; p<0.001), and QXR-600 mg (79%; p<0.001) compared with placebo (41%). The proportion of patients experiencing >= 7% weight gain was 4% for each lurasidone group, 15% for the QXR-600 mg group, and 3% for the placebo group. Endpoint changes in levels of cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol were comparable for both lurasidone groups and placebo, while the QXR-600 mg group showed a significant median increase compared with the placebo group in levels of cholesterol (p<0.001), LDL cholesterol (p<0.01), and triglycerides (p<0.05). Conclusions: Lurasidone 80 mg and 160 mg doses administered once-daily in the evening, were safe and effective treatments for subjects with acute schizophrenia, with increased response rates observed at the higher dose. Dose-related adverse effects were limited, and both doses were generally well-tolerated. (C) 2013 Elsevier B. V. All rights reserved.