Effects of Brexpiprazole on Agitation Associated with Dementia Due to Alzheimer’s Disease: Analysis of Pooled Response Data from Two Phase 3 Fixed-dose Trials
Saloni Behl1, Daniel Lee1, Jyoti Aggarwal1, Nanco Hefting2, Dalei Chen1, Denise Chang1
1Otsuka Pharmaceutical Development & Commercialization Inc., 2H. Lundbeck A/S
Objective:
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).
Background:
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.
Design/Methods:
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).
Results:
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).
Conclusions:
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.