A THREE ARM DOSE FINDING STUDY OF LURASIDONE: EFFICACY AND TOLERABILITY DATA

Abstract

Background: Lurasidone is a new atypical antipsychotic agent that has shown superiority to placebo in several registration trials. This compound has also shown a side effect profile notable for minimal metabolic effects and weight gain. Previous short-term, fixed dose studies have not examined daily doses below 40 mg and have been limited to inpatient samples. We report here an 8-week dose-response study of lurasidone that compared 20, 40, and 80 mg/d in a sample of inpatients and outpatients in Japan. Methods: Atotal of 200 patients with schizophrenia were randomized in double-blind fashion to fixed, single-daily doses of lurasidone for 8 weeks, followed by a 44-week extension period. Assessments included the PANSS, BPRS and CGI. Subjects were switched directly from previous medications without a washout period. If the daily dose of the previous antipsychotic medication exceeded 12 mg/day of haloperidolorits equivalent, the medication was tapered to the 12 mg/day equivalence level prior to switching. Safety assessments included a comprehensive movement disorder measure (DIEPSS), laboratory measures, weight, ECG and vital signs. Results: ANCOVA LOCF analyses demonstrated that single-daily doses of 40 and 80 mg of lurasidone were associated with significant improvements from baseline on the PANSS and the BPRS. The 40 mg/d dose was significantly superior to 20 mg/d on the BPRS. Drop out rates were equivalent across the dose arms, with more dropouts due to lack of efficacy for 20 mg and more for adverse events for the 80 mg dose. Serious adverse events were rare and 5/7 occurred at the 20 mg dose. All three dose arms were associated with decreases in weight that were less than 1.35 kg. In all three arms of the study, 2% or fewer of the patients gained 7% or more in their body weight. In an exploratory analysis for the total sample, patients treated 28 or more days had equivalent improvements across the three medication dosages. In addition, there was a linear apparent dose-response relationship for inpatients, with 80 mg superior, but for outpatients 40 mg appeared to be the optimal dose for clinical response. Discussion: This dose response study indicated that a 40 mg dose of lurasidone had optimal efficacy, but that all three doses had minimal side effects, particularly weight gain.