donepezil one-month depot (GB-5001) / G2GBIO - LARVOL DELTA

Population Pharmacokinetic Modeling and Simulation for Dose Optimization of GB-5001, a Long-Acting Intramuscular Injection of Donepezil, in Healthy Participants. (PubMed, Neurol Ther) - P1 | "The population PK model well explained the PKs of donepezil following administration of both the IM and oral formulations. This model could be applied for the design and dose selection of future BE trials."

Journal • PK/PD data • Alzheimer's Disease • CNS Disorders

Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics From Single Dose of Intramuscular (IM) and Subcutaneous (SC) Donepezil (GB-5001) Injections Versus Donepezil Oral Tablet (Aricept®) in Healthy Male Volunteers (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: G2GBio, Inc.

New P1 trial • Alzheimer's Disease • CNS Disorders

Comparative Pharmacokinetic Studies of One-Month Donepezil IM Depot and Once Daily Oral Tablet in Healthy Male Volunteers (AAIC 2023) - "A single dose of 70mg donepezil IM depot was found to be safe and well tolerated in healthy male volunteers. The pharmacokinetic results of 70mg donepezil IM depot showed stable donepezil blood concentration for more than one month without burst drug release, and showed comparable unit dose drug exposure not lower than that of once daily 10mg oral formulation. Through the PK results for additional higher doses and multiple PK simulations, optimal once monthly dose of donepezil IM depot could be suggested which will be bioequivalent to 10mg once daily tablet."

Clinical • PK/PD data • Alzheimer's Disease

Novel High-Donepezil Loaded One-Month Release Microspheres for Alzheimer’s Disease Treatment (AAIC 2023) - "We have developed novel donepezil microspheres with high drug contents and without initial burst release. These high donepezil-loaded microspheres can improve patient compliance and medication convenience by lowering dosage volume at the injection site. Currently, this novel donepezil formulation is planned for commercialization after clinical trials."

Alzheimer's Disease • CNS Disorders • Pain

Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Donepezil From Single Dose of GB-5001 IM Depot and Aricept® Oral Tablets in Healthy Male Volunteers (clinicaltrials.gov) - P1 | N=48 | Completed | Sponsor: G2GBio, Inc. | Recruiting ➔ Completed | Trial completion date: Sep 2023 ➔ Jun 2023

Trial completion • Trial completion date • Alzheimer's Disease • CNS Disorders

Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Donepezil From Single Dose of GB-5001 IM Depot and Aricept® Oral Tablets in Healthy Male Volunteers (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: G2GBio, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders

Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Donepezil From Single Dose of GB-5001 IM Depot and Aricept® Oral Tablets in Healthy Male Volunteers (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: G2GBio, Inc.

New P1 trial • Alzheimer's Disease • CNS Disorders

Donepezil ameliorates Aβ pathology but not tau pathology in 5xFAD mice. (PubMed, Mol Brain) - "However, neither intraperitoneal/oral injection of donepezil nor oral injection of rivastigmine altered tau phosphorylation at Thr212/Ser214 (AT100), Thr396, and Thr231 in 5xFAD mice. Surprisingly, we observed that intraperitoneal/oral injection of donepezil treatment significantly increased tau phosphorylation at Thr212 in 5xFAD mice. Taken together, these data suggest that intraperitoneal injection of donepezil suppresses Aβ pathology but not tau pathology in 5xFAD mice."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders

Donepezil Regulates LPS and Aβ-Stimulated Neuroinflammation through MAPK/NLRP3 Inflammasome/STAT3 Signaling. (PubMed, Int J Mol Sci) - "The acetylcholinesterase inhibitors donepezil and rivastigmine have been used as therapeutic drugs for Alzheimer's disease (AD), but their effects on LPS- and Aβ-induced neuroinflammatory responses and the underlying molecular pathways have not been studied in detail in vitro and in vivo. In a mouse model of AD (5xFAD mice), donepezil significantly reduced Aβ-induced microglial and astrocytic activation, density, and morphology. Taken together, our findings indicate that donepezil significantly downregulates LPS- and Aβ-evoked neuroinflammatory responses in vitro and in vivo and may be a therapeutic agent for neuroinflammation-associated diseases such as AD."

Journal • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • IL6