Long-term safety and tolerability of brexpiprazole for Japanese patients with agitation in Alzheimer's disease dementia: A multicenter, open-label study.

Background: The long-term safety and efficacy of brexpiprazole in Asian patients with agitation associated with dementia due to Alzheimer's disease are unknown. Objectives: To evaluate the safety of 14-week treatment with brexpiprazole 1 or 2 mg/day in Japanese patients who completed the 10-week double-blind treatment period in a parent phase 2/3 study, and to explore the efficacy of brexpiprazole. Methods: This was a phase 3 multicenter, open-label study (ClinicalTrials.gov Identifier NCT03724942, registered on 28 October 2018). Patients who had completed 10-week treatment of placebo, 1 or 2 mg/day of brexpiprazole in a parent study were rolled over into this extended study. The primary endpoint was the frequency of adverse events. Results: Of 183 patients with informed consent, 164 were treated with brexpiprazole 1 or 2 mg/day for 14 weeks (prior brexpiprazole subgroup: 102 patients, prior placebo subgroup: 62 patients), and the overall study completion rate was 71.3%. The overall incidence of treatment-emergent adverse events was 90.2% (in each subgroup, 90.2% and 90.3%, respectively). Most treatment-emergent adverse events were mild or moderate in severity, and no new safety signals were observed. Regarding the Cohen-Mansfield Agitation Inventory total score at Week 14 (last observation carried forward), the mean change from baseline (standard deviation) was -4.0 (9.8). Conclusions: The extended 14-week treatment with brexpiprazole 1 or 2 mg/day after 10-week treatment was generally well tolerated in Japanese patients with agitation associated with dementia due to Alzheimer's disease, and the efficacy was maintained.