Safety and Effectiveness of Lurasidone in Patients with Schizophrenia: A 12-Week, Open-Label Extension Study

Abstract

The goal of this study was to evaluate the safety and effectiveness of lurasidone among patients with schizophrenia in a 12-week open-label extension study. Patients and Methods: Patients who completed a 6-week, double-blind, placebo-controlled study were enrolled in a 12-week open-label extension study with flexible dosing of lurasidone at 40 or 80 mg/day. Safety assessments included adverse events, vital signs, laboratory tests, and electrocardiogram (ECG) parameters. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score, Clinical Global Impression-Severity Scale (CGI-S), Calgary Depression Scale for Schizophrenia (CDSS) and quality of life measure. Results: A total of 289 patients were enrolled in the open-label extension study. Rates of treatment-emergent adverse events (TEAEs) were low; akathisia was the most common TEAE with an incidence of 6.6%. There were 54 patients (18.7%) who discontinued the extension study, with 17 (5.9%) discontinuing due to adverse events. Minimal or no effects of lurasidone on weight, body mass index, metabolic parameters, prolactin, and ECG parameters were evident. There was continued improvement to week 12 in PANSS and CGI-S scores beyond the initial gains made during the prior 6-week double-blind study. Nonresponders to lurasidone 40 mg/day in the prior 6-week study showed a mean (standard deviation) improvement from open-label baseline of 10.7 (13.8) points on the PANSS total score after lurasidone dose was increased to a modal dose of 80 mg/day during the extension study. Changes from double-blind baseline in CDSS and quality of life were maintained in the extension study. Conclusion: Treatment with lurasidone 40 or 80 mg once daily (flexibly dosed) continued to be well tolerated with patients demonstrating further improvement in symptoms over the course of a 12-week open-label extension study in patients with schizophrenia.

Effectiveness of Lurasidone 80 mg in Patients with Schizophrenia: Results of an Open-Label, 12-Week Extension Study

“…Regarding efficacy, patients with schizophrenia who Similarly, greater improvement was also observed in both the subgroup that did not meet more stringent doubleblind response criteria (≥30% reduction in PANSS total score) and the subgroup with an open-label baseline PANSS total score ≥80. 16 In the ITT population, the positive, negative, and general psychopathology subscales of the PANSS all showed continued improvements during the extension phase in the modal 80 mg/d group. Both doses of lurasidone improved positive symptoms more than negative symptoms which is consistent with previous short-term double-blind trials.…”

“…Similarly, greater improvement was also observed in both the subgroup that did not meet more stringent double-blind response criteria (≥30% reduction in PANSS total score) and the subgroup with an open-label baseline PANSS total score ≥80. 16 …”

“…The data for present analysis were collected from the JEWEL Extension Study of lurasidone in people with schizophrenia (clinical trial registration: EudraCT Number: 2016–000061-23). 16 The JEWEL Extension Study was 12-week open-label extension study to evaluate the safety and effectiveness of lurasidone flexibly dosed at 40 mg/d or 80 mg/d. The JEWEL Extension Study followed a multicenter, randomized, double-blind, placebo-controlled, parallel-group 6-week study that was designed to evaluate the efficacy and safety of lurasidone 40 mg/d administered to patients (age 18–74) with acute schizophrenia (clinical trial registration: EudraCT number: 2016–000060-42).…”

“…13 Lurasidone is a drug with a pharmacological profile that acts as an antagonist for dopamine D2, serotonin (5-HT)7 and 5-HT2A receptors, and as a partial agonist for 5-HT1A receptors, with minimal binding affinity for histamine H1 and muscarinic M1 receptors. 14 In 2020, lurasidone 40 mg/d to 80 mg/d was approved in Japan for the treatment of schizophrenia based on the results of a 6-week double-blind, placebo-controlled study of the treatment of schizophrenia in some countries including Japan (JEWEL study; EudraCT number: 2016-000060-42), 15 a 12-week open-label extension study (JEWEL extension study; EudraCT number: 2016-000061-23), 16 and other clinical trials conducted in the USA and Europe countries. [17][18][19] Lurasidone has also been approved in Japan for the treatment of bipolar depression.…”

“…[20][21][22] A previous paper reported safety data for all patients (40 mg/d and 80 mg/d combined) during the open-label JEWEL extension study, and provided efficacy data on change in total symptomatology from open-label baseline for patients who received a modal dose of 40 mg/d or 80 mg/d during the 12-week extension phase. 16 Because the clinical decision of an increase to 80 mg/ d must be mindful of tolerability and safety, it is critical to examine tolerability and safety parameters for those who receive 80 mg/d separately from those who receive a lower dose. Moreover, the fact that negative symptoms adversely affect long-term functional outcomes in schizophrenia, 23 the impact of a dosage increase to 80 mg/d on a broad range of outcomes, including negative symptoms, is particularly relevant to decisions about dosage increases during longer-term treatment.…”