Effectiveness of lurasidone vs. quetiapine XR for relapse prevention in schizophrenia: a 12-month, double-blind, noninferiority study.

To evaluate the relapse prevention efficacy of lurasidone compared with quetiapine XR (QXR) in adults patients with schizophrenia. This double-blind study evaluated the relapse prevention efficacy of 12 months of flexible-dose treatment with lurasidone (40-160 mg/day) compared with QXR (200-800 mg/day), in outpatients with an acute exacerbation of chronic schizophrenia who had recently completed a 6-week placebo-controlled trial of treatment with either lurasidone or QXR. The primary endpoint, time-to-relapse, was analyzed using a Cox proportional hazards model in this noninferiority trial. The Kaplan-Meier estimate of the probability of relapse over 12 months was 23.7% for subjects receiving lurasidone vs. 33.6% for QXR. The hazard ratio [95% CI] for probability of relapse was 0.728 [0.410, 1.295] (log-rank p=0.280). Since the upper limit of the hazard ratio (1.295) was smaller than the prespecified noninferiority margin (1.93), noninferiority of lurasidone compared with QXR was demonstrated in this study. The probability of hospitalization at 12 months was lower for the lurasidone group compared with the QXR group (9.8% vs. 23.1%; log-rank p=0.049). A significantly higher proportion of lurasidone subjects achieved remission at study endpoint compared with the QXR group (61.9% vs. 46.3%; p=0.043). Discontinuation rates due to AEs were similar for lurasidone and QXR (7% vs. 5%). Treatment with lurasidone was not associated with clinically significant changes in weight or metabolic parameters. Twelve months of treatment with lurasidone met noninferiority criteria, and was associated with higher rates of remission, and reduced risk of hospitalization compared with QXR. No clinically significant effects on weight or metabolic parameters were observed during maintenance treatment with lurasidone.

Loebel A ，Cucchiaro J ，Xu J ，Sarma K ，Pikalov A ，Kane JM ... -  《-》

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.

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. 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). 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). 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.

Loebel A ，Cucchiaro J ，Sarma K ，Xu L ，Hsu C ，Kalali AH ，Pikalov A ，Potkin SG ... -  《-》

Annual cost of relapses and relapse-related hospitalizations in adults with schizophrenia: results from a 12-month, double-blind, comparative study of lurasidone vs quetiapine extended-release.

Rajagopalan K ，O'Day K ，Meyer K ，Pikalov A ，Loebel A ... -  《-》

Daytime sleepiness associated with lurasidone and quetiapine XR: results from a randomized double-blind, placebo-controlled trial in patients with schizophrenia.

Loebel AD ，Siu CO ，Cucchiaro JB ，Pikalov AA ，Harvey PD ... -  《-》

Long-term safety and tolerability of lurasidone in schizophrenia: a 12-month, double-blind, active-controlled study.

Citrome L ，Cucchiaro J ，Sarma K ，Phillips D ，Silva R ，Tsuchiya S ，Loebel A ... -  《-》