EHT0202 in Alzheimers Disease: A 3-Month, Randomized, Placebo- Controlled, Double-Blind Study
Abstract
BACKGROUND: EHT0202 (etazolate hydrochloride) is a new compound exhibiting both potential disease-modifying and symptomatic treatment properties in Alzheimer's Disease increasing alpha-secretase activity and sAPP alpha secretion, as well as acting as a GABA-A receptor modulator and as a PDE-4 inhibitor. METHODS: This pilot, randomized, double-blind, placebo-controlled, parallel group, multicentre, Phase IIA study was conducted in 159 randomized patients suffering from mild to moderate Alzheimer's Disease. EHT0202 (40 or 80 mg bid) or placebo was administered as adjunctive therapy to one acetylcholinesterase inhibitor over a 3-month period. This study was designed to assess the clinical safety and tolerability of EHT0202 as a primary objective, with secondary endpoints (cognitive function, daily living activities, behaviour, caregiver burden and global functioning) included to explore clinical efficacy of EHT0202 versus placebo. RESULTS: EHT0202 was shown to be safe and generally well tolerated. Dose-dependent numbers of early withdrawal and central nervous system related adverse events were observed. As expected, since the study was not powered and not designed to show drug efficacy, and except for ratings on the ADCS-ADL scale, no significant differences were seen between treatment groups. CONCLUSIONS: These first encouraging safety results do support further development of EHT0202 in order to assess its clinical efficacy and to confirm its tolerability in a larger cohort of Alzheimer patients and for a longer period.
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Etazolate (EHT0202) is an α-secretase modulator that acts as a selective GABA receptor modulator and was reported to have a safety profile with good tolerance in Alzheimer's disease patients.
“Etazolate (EHT0202) is listed as another α-secretase modulators which acts as a selective GABA receptor modulator. The agent was reported to have a safety profile with a good tolerance in AD patients (Vellas et al., 2011).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Vellas et al., 2011
A previous phase 2 trial showed etazolate was safe and well tolerated in patients with mild to moderate Alzheimer disease.
“A previous, phase 2 trial has showed that the agent was safe and well tolerated in patients with mild to moderate AD.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [48]
Etazolate (EHT0202) stimulates the nonamyloidogenic α-secretase pathway acting as a selective modulator of GABA receptors.
“Etazolate (EHT0202) stimulates the nonamyloidogenic α-secretase pathway acting as a selective modulator of GABA receptors.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [48]
Further evaluation of etazolate in phase 3 trials has not progressed.
“However, further evaluation of etazolate in phase 3 trials has not progressed.48”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [48]
Restricted knowledge assumes that α-secretase activation is promoted through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and may be through γ-aminobutyric acid (GABA) receptor signaling; thus, agents that activate the PI3K/Akt pathway or act as selective GABA receptor modulators are suggested as potential therapeutic drugs for Alzheimer disease.
“Restricted, nowadays, knowledge assumes that α-secretase activation is promoted through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and may be through γ-aminobutyric acid (GABA) receptor signaling; thus, agents that activate the PI3K/Akt pathway or act as selective GABA receptor modulators are suggested as potential therapeutic drugs for AD.47,48”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [48]
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- Authors
- Vellas, B., Sol, O., J. Snyder, P., Ousset, P.-J., Haddad, R., Maurin, M., Lemarie, J.-C., Desire, L., & P. Pando, M.
- Affiliations
- Inserm (FR)
- Venue
- Current Alzheimer Research
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2011-03-01
- Volume
- 8
- Issue
- 2
- Pages
- 203-212
- ISSN
- 1567-2050 (ISSN-L)
- OpenAlex
- W2101276626
- Cited by
- 133
- References
- 0
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 7 · 2023: 5 · 2022: 13 · 2021: 10 · 2020: 11 · 2019: 6 · 2018: 11 · 2017: 11 · 2016: 7 · 2015: 5 · 2014: 12 · 2013: 10 · 2012: 8
- Type
- conference abstract
- Language
- en
- Open access
- closed
- Locations
- Current Alzheimer Research (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, alpha-secretase, GABA-A receptor modulation, adjunctive therapy, acetylcholinesterase inhibitors, drug safety and tolerability, cognitive function, activities of daily living, behavior, caregiver burden, clinical efficacy
- MeSH terms
- Aged, Alzheimer Disease, Double-Blind Method, Etazolate, Female, Humans, Male, Phosphodiesterase Inhibitors, Pilot Projects, Time Factors
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