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[P2–034]: ARE ALZHEIMER's DRUG FAILURES DUE TO INACTIVE COMPOUNDS OR ARE WE DOING SOMETHING WRONG?
Author(s) -
Hendrix Suzanne,
Ellison Noel
Publication year - 2017
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 - 10.1016/j.jalz.2017.06.682
Subject(s) - blame , population , medicine , clinical trial , clinical endpoint , disease , homogeneous , equivalence (formal languages) , intensive care medicine , psychology , econometrics , clinical psychology , psychiatry , mathematics , environmental health , discrete mathematics , combinatorics
Background:SUVN-502 is a pure 5-HT6 receptor antagonist. It has good ADME properties and demonstrated robust efficacy in preclinical studies. SUVN-502 has excellent margin of safety in long-term preclinical toxicity studies. In healthy human subjects, SUVN-502 was well tolerated following single or multiple oral administrations. There were no clinically relevant or serious adverse events. Methods:SUVN-502 is being evaluated in a phase 2, proof of concept, 26 week, double blind, multicenter, randomized, parallel group, placebo controlled study. This study is regulated by US FDA. A total of 537 subjects with moderate Alzheimer’s disease receiving stable doses of Donepezil and Memantine are being recruited. Subjects will receive placebo or SUVN-502 (low or high dose) on top of donepezil and memantine for 26 weeks Rationale for phase 2 study: The effect of SUVN-502 + Donepezil + Memantine combination was evaluated for procognitive property (object recognition task), acetylcholine modulation (microdialysis) and theta modulation (electrophysiology). Results: Co-treatment of SUVN-502 with donepezil andmemantine significantly potentiated the procognitive effects when compared with memantine and donepezil treatment group in the object recognition task. These effects were seen even after repeated treatment for 14 days. SUVN-502 potentiated the effects of donepezil and memantine combination, in hippocampal acetylcholine levels and brain oscillatory activity. There were no significant changes in the exposures of SUVN-502 or donepezil or memantine. Conclusions: SUVN-502 + Donepezil + Memantine (Triple combination) represents a promising new approach for symptomatic treatment of Alzheimer’s disease.