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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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In the citing paper
“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
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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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FTIR and MS Evidence for Heavy Metal Binding to Anti-amyloidal NAP-Like Peptides
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“Aβ-metal interactions accelerate the formation of toxic oligomers responsible for the synaptic dysfunctions (Bush 2003; Roberson and Mucke 2006; Vellas et al. 2011).”
BackgroundLi, J., Guo, L., Cai, W., Mei, J., Liu, J., & Liu, Y. (2026) · Drug Delivery · doi:10.1080/10717544.2026.2645830 · Cited by 16
“An early clinical trial (NCT00880412) evaluated the oral α-secretase stimulant etazolate as an adjunctive therapy (Vellas et al. 2011; Singh et al. 2022), but oral administration is associated with gastrointestinal side effects and low BBB penetration.”
Amyloid cascade hypothesis, tau synthesis, and role of oxidative stress in AD
Vyas, J., Raytthatha, N., & Prajapati, B. G. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13205-6.00023-6 · Cited by 13
Receptor Targets in Alzheimer’s Disease Drug Discovery
Wallach, J. V., Colestock, T., & Adejare, A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802810-0.00006-4 · Cited by 11
Novel disease-modifying therapeutics for the treatment of Alzheimer’s disease
Léger, G. C., & Massoud, F. (2013) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.2013.811237 · Cited by 10
Pirolla, N. F. F., Batista, V. S., Viegas, F. P. D., Gontijo, V. S., McCarthy, C. R., Viegas, C., & Nascimento-Júnior, N. M. (2020) · Current Drug Targets · doi:10.2174/1389450121999200819144544 · Cited by 11
Targeting the awry Aβ pathway in Alzheimer’s disease: hype and hurdles
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“A clinical trial illustrated that etazolate was safe, well tolerated, and effective in treating AD (Vellas et al. 2011).”
Elsaman, T., Farès, M., Abdel‐Aziz, H. A., et al. (2013) · Journal of Chemistry · doi:10.1155/2013/463515 · Cited by 8
Maqbool, M., Rajvansh, R., Srividya, K., & Hoda, N. (2020) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2020.115640 · Cited by 8
Synthesis of Novel Pyrazolo[3,4-b]pyridines with Affinity for β-Amyloid Plaques
Vidali, V. P., Nigianni, G., Athanassopoulou, G. D., Canko, A., Mavroidi, B., Matiadis, D., Pelecanou, M., & Sagnou, M. (2022) · Molbank · doi:10.3390/m1343 · Cited by 9
Keshk, R. M. (2022) · Journal of Heterocyclic Chemistry · doi:10.1002/jhet.4517 · Cited by 8
Enfermedad de Alzheimer: nuevas estrategias terapéuticas
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Targeted Development of Pyrazoline Derivatives for Neurological Disorders: A Review
Chauhan, A., Salahuddin, S., Mazumder, A., et al. (2024) · ChemistrySelect · doi:10.1002/slct.202400738 · Cited by 7
Cunningham, E. L., & Passmore, A. P. (2013) · Maturitas · doi:10.1016/j.maturitas.2013.04.013 · Cited by 7
Alzheimer’s Disease Pharmacology
Plascencia‐Villa, G., & Perry, G. L. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00018-9 · Cited by 6
Amyloid β Hypothesis in the Development of Therapeutic Agents for Alzheimer’s Disease
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Wang, C., Wang, Z., Li, M., Li, C., Yu, H., Zhou, D.-S., & Chen, Z. (2017) · InTech eBooks · doi:10.5772/intechopen.69154 · Cited by 6
Alzheimer's disease: New therapeutic strategies
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Metadata
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › 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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