Brexpiprazole treatment for agitation in Alzheimer's dementia: A randomized study

Abstract

Introduction: We evaluated the efficacy and safety of brexpiprazole for the treatment of agitation in Alzheimer's dementia (AAD) in Japanese patients.

Methods: This was a phase 2/3 multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Patients with AAD were randomized to receive brexpiprazole 1 mg/day or 2 mg/day, or placebo (3:4:4) for 10 weeks.

Results: For the primary endpoint (change in Cohen-Mansfield Agitation Inventory [CMAI] total score from baseline to Week 10), both brexpiprazole 1 mg and 2 mg groups demonstrated statistically significant improvement versus placebo (2 mg: least squares [LS] mean difference -7.2 [95% confidence interval (CI): -10.0 to -4.3], p-value < 0.0001, 1 mg: LS mean difference -3.7 [95% CI: -6.8 to -0.7], p-value = 0.0175). The incidences of treatment-emergent adverse events reported in the brexpiprazole 1 mg, 2 mg, and placebo groups were 76.8%, 84.6%, and 73.8%, respectively.

Discussion: Brexpiprazole 1 mg/day and 2 mg/day for 10 weeks was efficacious and well tolerated.

Highlights: Brexpiprazole treatment for 10 weeks improved agitation in Alzheimer's dementia. The efficacy of brexpiprazole 1 mg/day has been confirmed for the first time. The incidence of adverse events was higher compared to the previous studies. Both brexpiprazole 1 mg/day and 2 mg/day were generally well tolerated.

Keywords: Alzheimer's disease; Japan; brexpiprazole; efficacy; safety.

FIGURE 1

Patient disposition. The safety analysis set consisted of patients who were randomized and administered at least one dose of study medication. The full analysis set consisted of patients who were randomized, administered at least one dose of study medication, and had a CMAI total score at baseline and at least one occasion after baseline. CMAI, Cohen‐Mansfield Agitation Inventory.

FIGURE 2

Changes in CMAI and CGI‐S total scores from baseline to Week 10 (FAS). (A) MMRM analysis. The mean (SD) CMAI total scores at baseline were 62.1 (11.3) for brexpiprazole 1 mg, 64.1 (12.9) for brexpiprazole 2 mg, and 62.7 (11.7) for placebo. (B) MMRM analysis. The mean (SD) CGI‐S total scores at baseline were 4.5 (0.8) for brexpiprazole 1 mg, 4.6 (0.9) for brexpiprazole 2 mg, and 4.6 (1.0) for placebo. The scale of CGI‐S is 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = among the most extremely ill patients. *p‐value < 0.05, **p‐value < 0.01, ***p‐value < 0.001. CGI‐S, Clinical Global Impression—Severity of Illness; CMAI, Cohen‐Mansfield Agitation Inventory; FAS, full analysis set; LS, least squares; MMRM, mixed models for repeated measures; SD, standard deviation; SE, standard error.

FIGURE 3

Change in CMAI subscale scores from baseline to Week 10 (FAS). MMRM analysis. Factor 1: aggressive behavior (both physical and verbal). Factor 2: physically nonaggressive behavior (excessive motor activity). Factor 3: verbally agitated behavior. *p‐value < 0.05, **p‐value < 0.01, ***p‐value < 0.001. CMAI, Cohen‐Mansfield Agitation Inventory; FAS, full analysis set; LS, least squares; MMRM, mixed models for repeated measures.