To evaluate the effect of masupirdine on Behavioral and Psychological Symptoms of Dementia (BPSD) in moderate AD patients.

Neuropsychiatric symptoms (NPS) are core features of Alzheimer’s disease (AD) and are distressing for patients and their caregivers. NPS are generally associated with risk and negative outcomes including early institutionalization. There are no FDA approved medications for the treatment of behavioral and psychotic symptoms.

Masupirdine (SUVN-502) is a selective 5-hydroxytryptamine-6 (5-HT6) receptor antagonist being investigated for the treatment of moderate AD.

Masupirdine was studied in a phase-2, multicenter, randomized, double-blind, parallel group, 26-week, placebo-controlled proof-of-concept study in subjects with moderate AD, receiving stable doses of donepezil and memantine. Participants received placebo or masupirdine (50 or 100 mg) with donepezil and memantine for 26 weeks. Behavioral outcomes were monitored with the Neuropsychiatric Inventory (NPI).

The mean (SD) NPI baseline score was 9.9 (10.2) consistent with the other studies not enriched for the neuropsychiatric symptoms. Treatment groups with masupirdine achieved better outcomes than placebo in the NPI scores. Masupirdine showed statistically significant reduction in the NPI agitation/aggression scores in the modified intent to treat population. In the subgroup of population who had baseline agitation/aggression, masupirdine showed statistically significant reduction in the agitation/aggression scores with respect to placebo at the end of 26 weeks. The treatment difference was above the minimum clinically important difference (0.4 SD). Similar outcome was also observed in the subgroup of population who had severe baseline agitation/aggression score (treatment difference was above the minimum clinically important difference). The effect observed with masupirdine on aggression/agitation sustained for the entire study duration of 26 weeks.

Masupirdine is generally well tolerated. Compared with placebo, masupirdine treatment improved behavioral symptoms as measured by NPI scores, agitation/aggression and delusions. Masupirdine may have a potential utility in the management of BPSD in AD.