Safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel AChE inhibitor: a single-center, phase I study in healthy young and elderly Chinese subjects

Background: Acetylcholinesterase (AChE) inhibitors attempt to reduce the breakdown of acetylcholine levels in the brain of patients with Alzheimer’s disease (AD) by inhibiting the responsible enzyme AChE in the synaptic cleft. This study evaluated the safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel AChE inhibitor under development for the treatment of AD in healthy young and elderly Chinese subjects. Methods The study on young subjects were divided into two arms: the multiple ascending-dose (MAD) arm (double-blind, randomized, placebo-controlled, multiple ascending-dose, 2 and 6 mg, N = 24), and the food effect arm (three-period, self-crossover, open-labeled, fasting/standard diet/high-fat diet administration, 4 mg, N = 12). A two-period, self-crossover, open-labeled, single ascending-dose study was designed for elderly subjects (2 and 4 mg, N = 11). Results For young subjects’ study: In the MAD arm, the accumulation ratios of DC20 in vivo were 2.29 and 2.15, respectively. In the food effect arm, compared with fasting administration, area under the concentration-time curve from zero to t (AUC 0-t ) orally after a standard diet and high-fat diet slightly increased by about 19% and 29% and the T max were delayed by around 1 hour. For elderly subjects’ study, T max were 1.5 and 1.25 hour, t 1/2 were 77.1 and 74.2 hour, respectively. After oral administration of DC20 in healthy young and elderly subjects, no serious adverse events occurred, the most common adverse events associated with the study drug were gastrointestinal reactions. Conclusion We predicted the safety risks of DC20 in the clinical treatment of AD, which were well tolerated by the healthy young and elderly subjects. The elimination of DC20 from the body was slower in elderly subjects than in young subjects. Trial registration numbers: CTR20181428, CTR20190664, CTR20191878, CTR20192724 approved by the Center for Drug Evaluation, National Medical Products Administration.