A first-in-human study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of KM-819 (FAS-associated factor 1 inhibitor), a drug for Parkinson's disease, in healthy volunteers.

BACKGROUND: KM-819 is a novel FAS-associated factor 1 (FAF1) inhibitor, and a neuroprotective agent, under clinical development for the treatment of Parkinson's disease as a disease-modifying drug. METHODS: This first-in-human, single and multiple ascending dose study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of KM-819 in healthy volunteers. Additionally, the effect of age on safety and pharmacokinetics were assessed. The starting dose was determined considering the no observed adverse effect level based on preclinical studies, and the dose escalations in subsequent cohorts were decided based on safety, tolerability, and pharmacokinetic data from previous dose cohorts. RESULTS: After a single dose, the KM-819 plasma exposure showed a less than dose-proportional increase across a dose range of 10-400 mg. After repeated dosing, KM-819 plasma exposure increased in an approximately dose-proportional manner across the evaluated dose range (30-400 mg once daily for 7 days). The mean elimination half-life was 1.8 to 4.8 h with the lower KM-819 doses (≤30 mg), which increased to around 9 h with the higher doses (100-400 mg). When administered to the elderly population, KM-819 plasma exposure increased to 102% after a 200 mg once-daily dosing for 7 days. No clear treatment-related effects on the estimated pharmacodynamic variables were observed. Single or multiple doses of KM-819 were generally well tolerated. CONCLUSION: The data from this study can be used to guide rational drug dosing and choose therapeutic regimens in subsequent clinical studies.

Palladium Nanoparticle-Decorated Porous Carbon Nanoflakes as High-Activity Catalyst for Electrooxidation of Alcohol.

A facile technique for the preparation of a multicomponent electrocatalyst that shows promising activity for the electrooxidation of alcohol has been demonstrated. The synthesis involves the preparation of hyper-crosslinked polydichloroxylene solid nanoflakes that are hybridized with PdCl2. The hybrid is reduced in an aqueous NaBH4 solution to fabricate Pd nanoparticle-decorated hyper-crosslinked polydichloroxylene. Finally, the polymer-supported palladium nanoparticles are subjected to thermal pyrolysis to form Pd-decorated carbon nanoflakes. The unique porous construction of these carbon nanoflakes result in high surface area and robust stability. The evaluation of the Pd-decorated carbon nanoflakes electrocatalyst shows improved performance and stability with high reaction efficiency for the electrooxidation of alcohols such as methanol.