The journal of prevention of Alzheimer's disease · 2022
Oral Tau Aggregation Inhibitor for Alzheimer's Disease: Design, Progress and Basis for Selection of the 16 mg/day Dose in a Phase 3, Randomized, Placebo-Controlled Trial of Hydromethylthionine Mesylate.
Рандомизированное исследованиеКлиническое исследование III фазыСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Wischik C M, Bentham P, Gauthier S, Miller S, Kook K, Schelter B O
Аннотация
BACKGROUND: Hydromethylthionine mesylate is a tau aggregation inhibitor shown to have exposure-dependent pharmacological activity on cognitive decline and brain atrophy in two completed Phase 3 trials in mild/moderate Alzheimer's disease (AD).
OBJECTIVES: The present report summarises the basis for selection of 16 mg/day as monotherapy as the optimal treatment regime and the design rationale of a confirmatory Phase 3 trial (LUCIDITY).
DESIGN: The trial comprises a 12-month double-blind, placebo-controlled phase followed by a 12-month modified delayed-start open-label treatment phase.
SETTING: 76 clinical research sites in North America and Europe.
PARTICIPANTS: 545 patients with probable AD or MCI-AD in the final version of the protocol.
INTERVENTION: Participants were assigned randomly to receive hydromethylthione mesylate at doses of 16 mg/day, 8 mg/day or placebo at a 4:1:4 ratio during the double-blind phase. All participants in the open-label phase receive the 16 mg/day dose.
MEASUREMENTS: Co-primary clinical outcomes are the 11-item Alzheimer's Disease Assessment Scale (ADAS-cog11) and the 23-item Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23). Secondary biomarker measures include whole-brain atrophy and temporal lobe 18F-fluorodeoxyglucose positron emission tomography.
RESULTS: 446 participants are expected to complete the 12-month placebo-controlled phase in March 2022.
CONCLUSIONS: If the primary end points are met, the data will provide confirmatory evidence of the clinical and biomarker benefits of hydromethylthionine mesylate in minimal to moderate AD. As low-dose oral hydromethylthionine mesylate is simple to use clinically, does not cause amyloid-related imaging abnormalities and has a benign safety profile, it would likely improve AD management.
OBJECTIVES: The present report summarises the basis for selection of 16 mg/day as monotherapy as the optimal treatment regime and the design rationale of a confirmatory Phase 3 trial (LUCIDITY).
DESIGN: The trial comprises a 12-month double-blind, placebo-controlled phase followed by a 12-month modified delayed-start open-label treatment phase.
SETTING: 76 clinical research sites in North America and Europe.
PARTICIPANTS: 545 patients with probable AD or MCI-AD in the final version of the protocol.
INTERVENTION: Participants were assigned randomly to receive hydromethylthione mesylate at doses of 16 mg/day, 8 mg/day or placebo at a 4:1:4 ratio during the double-blind phase. All participants in the open-label phase receive the 16 mg/day dose.
MEASUREMENTS: Co-primary clinical outcomes are the 11-item Alzheimer's Disease Assessment Scale (ADAS-cog11) and the 23-item Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23). Secondary biomarker measures include whole-brain atrophy and temporal lobe 18F-fluorodeoxyglucose positron emission tomography.
RESULTS: 446 participants are expected to complete the 12-month placebo-controlled phase in March 2022.
CONCLUSIONS: If the primary end points are met, the data will provide confirmatory evidence of the clinical and biomarker benefits of hydromethylthionine mesylate in minimal to moderate AD. As low-dose oral hydromethylthionine mesylate is simple to use clinically, does not cause amyloid-related imaging abnormalities and has a benign safety profile, it would likely improve AD management.