To explore response rates using pooled data from two fixed-dose trials of brexpiprazole in patients with agitation associated with dementia due to Alzheimer’s disease (AD).

Agitation symptoms are prevalent clinical manifestations of dementia due to AD, and reductions in agitation behavior frequency are considered reflective of meaningful improvement. Responder analyses – used here in relation to change in agitation – can support evaluation of clinical meaningfulness of clinical trial data.

The two brexpiprazole trials were Phase 3, 12-week, placebo-controlled, fixed-dose trials in patients with agitation associated with dementia due to AD (NCT01862640 [Study 283], NCT03548584 [Study 213]). In both trials, the Cohen-Mansfield Agitation Inventory (CMAI) (primary efficacy endpoint) and Clinical Global Impression – Improvement (CGI-I) as related to agitation (secondary endpoint) were assessed. Other pre-defined secondary/exploratory endpoints included CMAI response rate (≥40%, ≥30%, or ≥20% reduction from baseline to Week 12), and CGI-I response rate (score of 1 [very much improved] or 2 [much improved]). In this post hoc analysis, data for brexpiprazole 2 or 3 mg/day (FDA-approved recommended-to-maximum dose) were pooled from Studies 283 and 213, and compared with pooled placebo data (last observation carried forward).

This analysis included 363 patients randomized to brexpiprazole 2 or 3 mg/day, and 247 patients randomized to placebo. In the pooled sample, CMAI response rates for brexpiprazole versus placebo at Week 12 were: ≥40% reduction, 25.1% versus 14.2% (p=0.0003); ≥30% reduction, 42.7% versus 30.8% (p=0.0023); ≥20% reduction, 65.3% versus 50.6% (p=0.0014). CGI-I response rates at Week 12 were 51.2% with brexpiprazole versus 43.3% with placebo (p=0.047).

Across two fixed-dose trials of patients with agitation associated with dementia due to AD, a greater proportion of patients treated with brexpiprazole 2 or 3 mg/day versus placebo achieved pre-defined criteria for agitation response.