ArticleAlzheimer's & dementia (New York, N. Y.)2019
A 24-week double-blind placebo-controlled study of the efficacy and safety of the AMPA modulator S47445 in patients with mild to moderate Alzheimer's disease and depressive symptoms.
Article in Alzheimer's & dementia (New York, N. Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02626572 (Efficacy and Safety of 3 Doses of S47445 Versus Placebo in Patients With Alzheimer's Disease at Mild to Moderate Stages With Depressive Symptoms. A 24-week International, Multi-centre, Randomized, Double-blind, Placebo-controlled Phase II Study in Monotherapy Followed by an Optional 28-week Extension Period in Co-administration With Donepezil.), which is not on this map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Efficacy and Safety of 3 Doses of S47445 Versus Placebo in Patients With Alzheimer's Disease at Mild to Moderate Stages With Depressive Symptoms. A 24-week International, Multi-centre, Randomized, Double-blind, Placebo-controlled Phase II Study in Monotherapy Followed by an Optional 28-week Extension Period in Co-administration With Donepezil.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effect of N-methyl-D-aspartate receptor enhancing agents on cognition in dementia: an exploratory systematic review and meta-analysis of randomized controlled trials.Scientific reports · 2021Pooled it
- Neuropsychological, neuropsychiatric, and quality-of-life assessments in Alzheimer's disease patients treated with plasma exchange with albumin replacement from the randomized AMBAR study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Trial
- Positive AMPA and Kainate Receptor Modulators and Their Therapeutic Potential in CNS Diseases: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Amplification of the therapeutic potential of AMPA receptor potentiators from the nootropic era to today.Pharmacology, biochemistry, and behavior · 2025Review
- Efficacy of medications in controlling cognitive dysfunction in Alzheimer's : a systematic review.Dementia & neuropsychologia · 2025Review
- Bridging rapid and sustained antidepressant effects of ketamine.Trends in molecular medicine · 2023Review
- Dysfunction of Glutamatergic Synaptic Transmission in Depression: Focus on AMPA Receptor Trafficking.Biological psychiatry global open science · 2023Review
- Diversity of AMPA Receptor Ligands: Chemotypes, Binding Modes, Mechanisms of Action, and Therapeutic Effects.Biomolecules · 2022Review
- Positive AMPA receptor modulation in the treatment of neuropsychiatric disorders: A long and winding road.Drug discovery today · 2021Review
- Allosteric modulation of AMPA receptors counteracts Tau-related excitotoxic synaptic signaling and memory deficits in stress- and Aβ-evoked hippocampal pathology.Molecular psychiatry · 2021Article
- Chronic Stress and Oxidative Stress as Common Factors of the Pathogenesis of Depression and Alzheimer's Disease: The Role of Antioxidants in Prevention and Treatment.Antioxidants (Basel, Switzerland) · 2021Review
- NMDA and AMPA Receptor Autoantibodies in Brain Disorders: From Molecular Mechanisms to Clinical Features.Cells · 2021Review
- Acetylation of AMPA Receptors Regulates Receptor Trafficking and Rescues Memory Deficits in Alzheimer's Disease.iScience · 2020Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
introductionS47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors that may emerge as a favorable candidate for the symptomatic treatment of cognitive and depressive disorders in patients suffering from Alzheimer's disease (AD) of mild to moderate severity and with depressive symptoms.
methodsFor this double-blind, placebo-controlled 24-week phase II trial, 520 outpatients aged between 55 and 85 years, with probable AD at mild to moderate stages (a Mini-Mental State Examination score of 24-15 inclusive) and exhibiting depressive symptoms (Cornell Scale for Depression in Dementia [CSDD] ≥ 8) were recruited in twelve countries and randomized to 3 doses of S47445 (5-15-50 mg) or placebo. The primary end point was the change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) total score at week 24. Secondary measures included the Disability Assessment for Dementia, Mini-Mental State Examination, ADAS-Cog 13-item, CSDD, Clinical Global Impression of Change (Alzheimer's Disease Cooperative Study-CGIC), Neuropsychiatric Inventory (NPI), and safety criteria.
resultsBaseline characteristics were comparable between the 4 groups. After 24 weeks, no statistically significant treatment difference was demonstrated between S47445 (5, 15 or 50 mg/d) and placebo on cognition (ADAS-Cog), function (Disability Assessment for Dementia), or depressive symptoms (CSDD). An improvement on neuropsychiatric symptoms assessed by NPI was evidenced at the lower dose 5 mg/d (Δ -2.55, DISCUSSION: S47445 administered for 24 weeks was safe and well tolerated by patients with mild to moderate AD; the compound did not show significant benefits over placebo on cognition, function, or depressive symptoms.
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