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Randomized Controlled Trial
. 2016 Jan;30(1):69-77.
doi: 10.1177/0269881115620460. Epub 2015 Dec 8.

A double-blind, placebo-controlled, randomized withdrawal study of lurasidone for the maintenance of efficacy in patients with schizophrenia

Rajiv Tandon  1 , Josephine Cucchiaro  2 , Debra Phillips  2 , David Hernandez  2 , Yongcai Mao  2 , Andrei Pikalov  2 , Antony Loebel  2
Affiliations
Randomized Controlled Trial

A double-blind, placebo-controlled, randomized withdrawal study of lurasidone for the maintenance of efficacy in patients with schizophrenia

Rajiv Tandon et al. J Psychopharmacol. 2016 Jan.

Abstract

Objective: To evaluate the effectiveness of lurasidone as maintenance treatment for schizophrenia.

Method: Adults experiencing an acute exacerbation of schizophrenia initially received 12-24 weeks of open-label treatment with lurasidone (40-80 mg/d, flexibly dosed). Patients who maintained clinical stability for ⩾12 weeks were randomized in double-blind fashion to placebo or lurasidone (40-80 mg/d, flexibly dosed) for an additional 28-week treatment period. The primary efficacy endpoint was time to relapse (based on Kaplan-Meier survival analysis).

Results: A total of 676 patients enrolled in the open-label phase; 285 met protocol-specified stabilization criteria and were randomized to lurasidone (N=144) or placebo (N=141). During the open-label phase, mean Positive and Negative Syndrome Scale total score decreased from 90.1 to 54.4 in patients who met clinical stability criteria and were randomized. In the double-blind phase, lurasidone significantly delayed time to relapse compared with placebo (log-rank test, p=0.039), reflecting a 33.7% reduction in risk of relapse (Cox hazard ratio (95% confidence interval), 0.663 (0.447-0.983); p=0.041). Probability of relapse at the double-blind week 28 endpoint (based on Kaplan-Meier analysis) was 42.2% in the lurasidone group and 51.2% in the placebo group. Minimal changes in weight, lipid, glucose, and prolactin were observed throughout the study.

Conclusions: This multicenter, placebo-controlled, randomized withdrawal study demonstrated the efficacy of lurasidone for the maintenance treatment of patients with schizophrenia.

Keywords: Lurasidone; antipsychotic agents; drug therapy; maintenance treatment; relapse prevention; schizophrenia.

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Conflict of interest statement

Declaration of Conflicting Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Rajiv Tandon has served as an honorary consultant for Sunovion Pharmaceuticals, Inc.

Josephine Cucchiaro, Debra Phillips, David Hernandez, Yongcai Mao, Andrei Pikalov, and Antony Loebel are employees of Sunovion Pharmaceuticals, Inc.

Figures

Figure 1.
Figure 1.
Study design.
Figure 2.
Figure 2.
Patient disposition. AE: adverse event.
Figure 3.
Figure 3.
Kaplan–Meier survival curve of time to relapse. Time to relapse was censored at the time of study completion or early termination for patients who discontinued from or completed the double-blind phase without experiencing a relapse event.
Figure 4.
Figure 4.
Change in PANSS total score (a) and CGI-S score (b) in the open-label phase and double-blind phase (ANCOVA, LOCF) among patients who met criteria for clinical stability and were randomized. *p<0.05. **p<0.01. ***One patient in the lurasidone group did not have a post-baseline assessment. ANCOVA: analysis of covariance; BL: baseline; CGI-S: Clinical Global Impression-Severity; DB: double-blind; LOCF: last observation carried forward; LS: least-squares; OL: open-label; PANSS: Positive and Negative Syndrome Scale.
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