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

Abstract

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.

Keywords: Alzheimer's disease; Japan; brexpiprazole; long-term; safety.

Figure 1.

Study design. Eligible patients who provided informed consent were rolled over from the parent double-blind study to this study. Brexpiprazole was initiated at 0.5 mg (Day 1), increased to 1 mg in Week 1 (Day 8), and was flexibly administered at 1 or 2 mg onwards until Week 14 (Day 99). Brexpiprazole was taken orally once daily, preferably at the same time each day, regardless of meals. Visits occurred at Day 1 (Week 10 of the parent study [baseline]), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, or at study discontinuation, and within 28 days after Day 99 or study discontinuation for follow-up assessment. Concomitant medications of antidementia drugs, narcotic analgesics, beta blockers, and sleeping drugs were allowed with restrictions (Supplemental Table 1). Brex: brexpiprazole; DB: double-blind.

Figure 2.

Patient disposition. The safety analysis set consisted of patients who were administered at least one dose of study treatment. The efficacy analysis set consisted of patients who were administered at least one dose of study treatment and had a CMAI total score at baseline and at least one occasion after baseline. Brex: brexpiprazole; CMAI: Cohen-Mansfield Agitation Inventory.