Safety, Tolerability, and Efficacy of Brexpiprazole for the Treatment of Agitation Associated with Dementia Due to Alzheimer’s Disease: A 12-week Extension Trial
George Grossberg1, Daniel Lee2, Mary Slomkowski2, Nanco Hefting3, Dalei Chen2, Mary Hobart2, Jeffrey Cummings4
1Department of Psychiatry and Behavioral Neuroscience at Saint Louis University School of Medicine, 2Otsuka Pharmaceutical Development & Commercialization Inc., 3H. Lundbeck A/S, 4Chambers-Grundy Center for Transformative Neuroscience at University of Nevada Las Vegas (UNLV) School of Integrated Health Sciences
Objective:
To assess the long-term safety, tolerability, and efficacy of brexpiprazole in patients with agitation associated with dementia due to Alzheimer’s disease (AD).
Background:
Agitation symptoms are common in AD, and are among the most challenging aspects of care. Brexpiprazole is FDA-approved for the treatment of agitation associated with dementia due to AD, making it the first approved medication for this indication in the US.
Design/Methods:
Study 182 was a 12-week, multicenter, single-arm brexpiprazole extension trial (NCT03594123), which enrolled patients who completed a 12-week, placebo-controlled trial of brexpiprazole 2 or 3 mg/day in patients with agitation associated with dementia due to AD (NCT03548584 [Study 213]). In Study 182, all patients received brexpiprazole 2 or 3 mg/day; dosing was blinded. Assessments of long-term safety and tolerability (primary objective) included treatment-emergent adverse events (TEAEs), suicidality, and body weight. Both studies evaluated efficacy using the Cohen-Mansfield Agitation Inventory (CMAI) and Clinical Global Impression − Severity (CGI-S) as related to agitation.
Results:
A total of 259 patients entered Study 182 (prior brexpiprazole, n=163; prior placebo, n=96). The overall incidence of TEAEs was 25.9% (prior brexpiprazole, 25.2%; prior placebo, 27.1%); 4.6% of patients discontinued due to adverse events. TEAEs with an overall incidence ≥2% were headache (3.5%) and fall (2.3%). There were no deaths in Study 182, and no reports of suicidal behavior/ideation. The mean (standard deviation) change in body weight from Study 182 baseline to Week 12 was 0.2 (5.6) kg. In Study 213, brexpiprazole demonstrated greater improvement (p<0.01) versus placebo in CMAI Total and CGI-S scores at Week 12. In Study 182, continued improvements in CMAI Total and CGI-S scores were observed.
Conclusions:
In patients with agitation associated with dementia due to AD, brexpiprazole 2 or 3 mg/day was well-tolerated and efficacious throughout up to 24 weeks of treatment.