Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Positive Modulator of HGF/MET, Fosgonimeton, in Healthy Volunteers and Subjects with Alzheimer's Disease: Randomized, Placebo-Controlled, Double-Blind, Phase I Clinical Trial.
Background: Fosgonimeton (ATH-1017) is being developed as a first-in-class regenerative therapy for people with Alzheimer's disease (AD) and dementia; potentially improving dementia symptoms and altering disease progression by reversing synaptic disconnection and neuronal loss.Objective: This random...
| Publicado en: | Journal of Alzheimer's Disease Vol. 86; no. 3; pp. 1399 - 1414 |
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| Autores principales: | , , , , , , , |
| Formato: | clinical trial research randomized controlled trial Journal Article |
| Publicado: |
Sage Publications Inc.
2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=156157750&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 156157750 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 13872877 FLR jtl: Journal of Alzheimer's Disease issn: 13872877 maglogo: N pubinfo: dt: 2022 vid: 86 iid: 3 pid: 20732 pub: Sage Publications Inc. place: Thousand Oaks, California artinfo: ui: 156157750 156157750 NLM35180125 156157750 10.3233/JAD-215511 NLM35180125 156157750 ppf: 1399 ppct: 15 formats: tig: atl: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Positive Modulator of HGF/MET, Fosgonimeton, in Healthy Volunteers and Subjects with Alzheimer's Disease: Randomized, Placebo-Controlled, Double-Blind, Phase I Clinical Trial. aug: au: Hua, Xue Church, Kevin Walker, William L'Hostis, Philippe Viardot, Geoffrey Danjou, Philippe Hendrix, Suzanne Moebius, Hans J. affil: Athira Pharma, Inc., Bothell, WA, USA sug: subj: Alzheimer's Disease Drug Therapy Human Double-Blind Studies Pharmacokinetics Cytokines Therapeutic Use Male Aged Research Subjects Dose-Response Relationship, Drug Clinical Trials Comparative Studies Multicenter Studies Randomized Controlled Trials Evaluation Research Validation Studies Aged: 65+ years Male ab: Background: Fosgonimeton (ATH-1017) is being developed as a first-in-class regenerative therapy for people with Alzheimer's disease (AD) and dementia; potentially improving dementia symptoms and altering disease progression by reversing synaptic disconnection and neuronal loss.Objective: This randomized, double-blind, placebo-controlled phase I trial (NCT03298672) evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of fosgonimeton.Methods: Fosgonimeton was administered once daily via subcutaneous injection to 88 subjects. The single ascending dose study enrolled healthy young male subjects (n = 48; age, 33.4±6.3 years; dose, 2, 6, 20, 40, 60, or 90 mg); the multiple ascending dose study enrolled healthy elderly subjects (n = 29; age, 63.8±4.0 years; dose, 20, 40, 60, or 80 mg; 9-day duration); and the fixed-dose study enrolled AD subjects (n = 11; age, 69.2±7.1 years; dose, 40 mg; 9-day duration). Quantitative electroencephalogram (qEEG) and event-related potential (ERP) P300 measured neurophysiological signals following fosgonimeton treatment, supporting brain penetration and target engagement.Results: Fosgonimeton and placebo were shown to be safe and well-tolerated across all doses. Pharmacokinetic results for fosgonimeton were dose-proportional, with no sex effect or accumulation over 9 days. The main effect of fosgonimeton on qEEG was acute and sustained gamma power induction. In AD subjects, there was a significant effect toward ERP P300 latency normalization compared with placebo (p = 0.027; n = 7 at 40 mg fosgonimeton versus n = 4 placebo).Conclusion: These results support the continued development of fosgonimeton as a novel therapeutic for people with AD and dementia. The fast-onset normalization of ERP P300 latency in AD subjects suggests enhancement of synaptic function and potential procognitive effects. pubtype: Academic Journal doctype: clinical trial research randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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