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Masupirdine (SUVN‐502): Novel treatment option for the management of behavioral and psychological symptoms in patients with Alzheimer’s disease
Author(s) -
Nirogi Ramakrishna,
Jayarajan Pradeep,
Shinde Anil K,
Abraham Renny,
Goyal Vinod Kumar,
Benade Vijay,
Ravulu Jyothsna,
Jasti Venkat
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.039303
Subject(s) - memantine , psychosis , donepezil , psychology , placebo , randomized controlled trial , medicine , psychiatry , disease , dementia , alternative medicine , pathology
Background 5‐hydroxytryptamine‐6 (5‐HT 6 ) receptors are G‐protein coupled receptors localized in the brain regions primarily involved in cognition and behavior i.e., cortex, dorsal hippocampus and striatum. Evidence from the studies in animal models suggests that 5‐HT 6 receptor antagonist may have a potential role in controlling behavior and psychosis. Masupirdine is a pure 5‐HT 6 receptor antagonist under clinical development for the management of AD and behavioral and psychological symptoms. Method Triple therapy with masupirdine added to background dual combination treatment with donepezil and memantine was evaluated in a phase‐2 proof‐of‐concept, 26‐week, randomized, double‐blind, placebo‐controlled, multicenter, parallel groups study conducted across several sites in the United States. In this study, effects of masupirdine on the neuropsychiatric symptoms and cognition were evaluated using the Neuropsychiatric Inventory (NPI‐12) and Alzheimer's Disease Assessment Scale–Cognitive subscale (ADAS‐Cog 11), respectively in patients with moderate AD. Result Out of 564 randomized patients, 183 patients received placebo, 184 patients received 50 mg of masupirdine and 176 patients received 100 mg of masupirdine. Masupirdine attenuated the agitation/aggression scores in the subgroup of patients who had baseline agitation/aggression. The effect observed was above the minimum clinically important difference (0.4 SD). In another subgroup of patients, masupirdine attenuated the psychotic symptoms (delusions and hallucinations) and also emergence of psychotic symptoms. Significant reduction in the cognitive decline was also noticed with masupirdine treatment in the subgroups of patients having psychotic symptoms. Masupirdine was generally safe and well tolerated in this study. Conclusion Masupirdine treatment significantly reduced the behavioral and psychological symptoms i.e., agitation/aggression and psychotic symptoms (delusions and hallucinations) with positive effect on cognition. Masupirdine could be a differentiated novel therapeutic treatment option for the management of behavioral and psychological symptoms in patients with AD.