To evaluate the effect of masupirdine on agitation/aggression and psychosis sub-domains of the 12-item neuropsychiatric inventory (NPI-12) scale in patients with dementia of the Alzheimer’s type (AD).

AD is the most common type of neurodegenerative disorder in older people. Cognitive and neuropsychiatric symptoms are the cardinal clinical features of the disease. Masupirdine has beenevaluated in arandomized, double-blind, 26-week, placebo-controlled proof of concept Phase-2 clinical trial in subjects with moderate AD (NCT02580305).

Subgroup analyses were carried out on the agitation/aggression, and psychosis domains of the NPI-12 scale.Analyses were based on the independent patient subgroups with baseline symptoms. A mixed-effects model for repeated measures was used to determine the effect of masupirdine in modified intention to treat population.

A statistically significant (p<0.01) reduction in agitation/aggression scores was observed in patients treated with masupirdine (50 & 100 mg) at Week 13 andthe effect sustained till the end of treatment (Week26). Clinically meaningful effect(Cohen's d - 0.66) wasobserved in the masupirdine 50 mg treatment arm at Week 26.

In the subgroup of population with baseline psychotic symptoms and/or symptoms emergence, a significant reduction (p<0.05) in psychosis score was observed in the masupirdine 50 mg arm at Week 4 & 13. A trend was observed in the masupirdine 100 mg (p<0.1) arm (Week 26). Effect size (Cohen's d) observed with masupirdine (50 & 100 mg) was 0.32 - 0.50 and 0.25 - 0.39 at the end of 13 and 26 weeks, respectively. Masupirdine had also showed beneficial effects on cognition in patients with psychosis.

Further exploration of masupirdine is warranted to confirm the beneficial effects on agitation and psychosis. Currently, a Phase-3 study evaluating the effect of masupirdine on agitation in patients with dementia of the Alzheimer's type is in progress.