Efficacy, Safety and Tolerability of Brexpiprazole for the Treatment of Agitation in Alzheimer’s Dementia: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial

Abstract: Background: Agitation is common in Alzheimer’s dementia, and one of the most stressful aspects of care. The aim of this study was to confirm the efficacy, safety and tolerability of brexpiprazole in patients with agitation in Alzheimer’s dementia. Methods: This was a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm study (NCT03548584). Eligible patients were aged 55–90 years, in a care facility or community-based setting, had a diagnosis of probable Alzheimer’s disease, and met criteria for agitation (International Psychogeriatric Association [IPA] criteria). Patients were randomized 2:1 to brexpiprazole (further randomized 1:2 to fixed-dose 2 mg/day or 3 mg/day) or placebo. Stable background medications for Alzheimer’s disease were permitted. The primary endpoint was change from baseline to Week 12 in Cohen–Mansfield Agitation Inventory (CMAI) Total score. The key secondary endpoint was change from baseline to Week 12 in Clinical Global Impression − Severity of illness (CGI-S) score, as related to agitation. Safety was also assessed. Results: 345 patients were randomized. The mean change from baseline to Week 12 in CMAI Total score was greater with brexpiprazole (2 mg/day or 3 mg/day) versus placebo (p=0.0026). Separation between brexpiprazole and placebo was also observed on the key secondary endpoint (p=0.0055). Aside from headache (6.6%), no other treatment-emergent adverse events had an incidence ≥5% in the brexpiprazole group. Conclusion: In patients with agitation in Alzheimer’s dementia, brexpiprazole was associated with reduced agitation versus placebo, supporting the findings of two prior clinical trials. Brexpiprazole was generally well tolerated, and no new safety signals were observed.Short Description: This Phase 3, randomized, double-blind, placebo-controlled, parallel-arm study (NCT03548584) evaluated the efficacy, safety and tolerability of brexpiprazole 2 or 3 mg/day in patients with agitation in Alzheimer’s dementia. Brexpiprazole separated from placebo on the primary endpoint of mean change from baseline to Week 12 in Cohen–Mansfield Agitation Inventory Total score (p=0.0026). Brexpiprazole was generally well tolerated, and no new safety signals were observed.Name of Sponsoring Organization(s): Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, NJ, USA, and H. Lundbeck A/S, Valby, Denmark