A phase 3 trial has been initiated to further study masupirdine’s effect on agitation in patients with Alzheimer dementia.
Findings from the phase 2a multicenter, randomized, double-blind, proof-of-concept trial (NCT02580305) were presented at the 14th Clinical Trials on Alzheimer’s Disease Conference (CTAD), November 9-12, 2021. The study spanned a total of 26 weeks, with patients receiving a 50-mg dose of masupirdine, a 100-mg dose of masupirdine, or placebo.
Investigators, led by Ramakrishna Nirogi, PhD, vice president, Suven Life Sciences, conducted subgroup analyses on the agitation/aggression domain of the 12-item neuropsychiatric inventory scale (NPI-A/A), based on independent patient subgroups and baseline symptoms. Patients who had a baseline NPI-A/A score of 1 point or greater were randomized to receive placebo (n = 57), masupirdine 50 mg (n = 54), or masupirdine 100 mg (n = 48). A significant mean change from baseline was identified in both the 50 mg (P <.001) and 100 mg (P = .007) groups when compared with placebo at week 26.
Similarly, in the group of patients with a baseline NPI-A/A score of 3 points or higher, investigators observed a significant mean change from baseline in the masupirdine 50-mg group (n = 30) at both week 13 (P = .012) and week 26 (P = .031) when compared with placebo. A significant change was also seen in the masupirdine 100-mg group (n = 21) at week 26, when compared with placebo (P = .024). Also noted were sustained effects of masupirdine for the entirety of the 26-week study, with no evidence of sedation in relation to treatment observed.
A phase 3 study has been initiated to further study masupirdine’s effect on agitation with Alzheimer dementia, enrolling approximately 387 patients for a study period of 36 months. Topline results are anticipated to be presented by the end of 2024.2
Masupirdine demonstrated a significant attenuation of psychosis in patients with dementia, representing a potential new treatment option for this patient population. In a separate presentation at CTAD, investigators presented additional findings the phase 2a study, which included 564 patients with moderate AD. While the study did not meet its primary end point, 2 potential beneficial effects on cognitive and behavioral outcomes were observed, providing motivation for additional sub-analyses considering combinations of patients’ age, memantine regimen, memantine plasma concentration, memantine treatment duration, and AD duration.
Patients in each group were evaluated on domains of the NPI-12. Using a mixed-effects model for repeated measures, the effect size (Cohen d) on psychosis in the masupirdine treatment groups were 0.31-0.58 at the end of week 13 and between 0.24-0.35 at the conclusion of the 26-week treatment period.
The study authors concluded that the treatment "may have potential to address limitations of current pharmacological interventions." At baseline, those in the 50- and 100-mg groups had Alzheimer’s Disease Assessment Scale for Cognitive Behavior scores of 29.62 (standard deviation [SD], 8.14) and 31.40 (SD, 9.17), respectively. At the end of the 26-week treatment period, the effect size on cognition with masupirdine treatment was between 0.48-0.57.3
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