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

AbstractBackgroundAgitation is a prevalent clinical manifestation of Alzheimer’s dementia, and is one of the most stressful aspects of care in patients affected by the disease. However, currently, there are no FDA‐approved pharmacological treatments for agitation in this patient population. Following two prior clinical trials of brexpiprazole in this patient population, the aim of this study was to confirm the efficacy, safety and tolerability of brexpiprazole in patients with agitation in Alzheimer’s dementia.MethodsThis 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 as defined by the International Psychogeriatric Association (IPA). Patients were randomized 2:1 to brexpiprazole or placebo; within the brexpiprazole arm, patients were further randomized 1:2 to fixed‐dose 2 mg/day or 3 mg/day. Stable background medications for the treatment of 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.ResultsA total of 345 patients were randomized to brexpiprazole or placebo. On the primary endpoint, the mean change from baseline to Week 12 in CMAI Total score was statistically significantly greater in the brexpiprazole group (2 mg/day or 3 mg/day) versus the placebo group (p = 0.0026). Statistically significant separation between the brexpiprazole and placebo groups was also observed on the key secondary endpoint of change from baseline to Week 12 in CGI‐S score (p = 0.0055). Aside from headache (6.6%), no other treatment‐emergent adverse events occurred with an incidence ≥5% in the brexpiprazole group.ConclusionIn this Phase 3 study of patients with agitation in Alzheimer’s dementia, treatment with brexpiprazole was associated with a statistically significantly greater reduction in agitation, and improvement in clinical global impression of agitation, compared with placebo, supporting the findings of two prior clinical trials. Brexpiprazole was generally well tolerated, and no new safety signals were observed.