Efficacy and Safety of Lurasidone in Phase 2/3 Acute Schizophrenia Trials

Josephine Cucchiaro, PhD; Antony Loebel, MD; Robert Silva, PhD; Debra Philips, MS; Masaaki Ogasa, MS; and Jane Xu, PhD
Dainippon Sumitomo Pharma America, Inc, Fort Lee, New Jersey

This poster presentation was supported by Dainippon Sumitomo Pharma America Inc.

Background: Lurasidone is a novel psychotropic agent with high affinity for D2 and 5-HT2A receptors, as well as for receptors implicated in the enhancement of cognition, mood, and negative symptoms (5-HT7, 5-HT1A and α2c). The objective of the studies discussed here was to assess the efficacy and safety of lurasidone in the treatment of patients hospitalized for an acute exacerbation of schizophrenia.

Methods: Data were obtained from three randomized, double-blind, placebo-controlled trials: two Phase II studies (total N=329) and one Phase III study (total N=500) in which patients meeting DSM-IV criteria for an acute exacerbation of schizophrenia were randomized to six weeks of double-blind treatment with a fixed daily dose of lurasidone 40 mg, 80 mg, or 120 mg. Cohen's d effect sizes were calculated for baseline to week 6 change in Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale-derived (BPRSd) total scores. The potential dose-response of lurasidone was also evaluated using a linear dose-response model.

Results: In the Phase II trials, effect sizes of BPRSd at endpoint were higher on the 120 mg dose of lurasidone (0.78) compared to the 40 mg (0.43) and 80 mg (0.42) doses. Results from the Phase III study support the potential for a greater treatment effect at higher doses. Lurasidone was generally well-tolerated with few discontinuations due to adverse effects and minimal effects on weight, lipids, and glucose.

Conclusions: The results of these placebo-controlled studies in patients with acute schizophrenic illness suggest that lurasidone is efficacious and well-tolerated in a dose range of 40–120 mg/day.

References
Ishiyama T, Tokuda K, Ishibashi T, et al. Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test. Eur J Pharmacol. 2007;572(2–3):160–170.

Enomoto T, Ishibashi T, Tokuda K, et al. Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats. Behav Brain Res. 2008;186(2):197–207.

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