Publication: Clinical Drug Investigation
Abstract
MN-08, a nitrate derivative of memantine, is being developed as a treatment for pulmonary arterial hypertension, a rare and progressive disease with limited therapeutic options. This Phase I, randomized, double-blind, placebo-controlled study evaluated the safety, tolerability, and pharmacokinetics of MN-08 in healthy Chinese volunteers using single ascending dose, multiple ascending dose, and food-effect crossover designs, with pharmacokinetic parameters derived by non-compartmental analysis in Phoenix WinNonlin. MN-08 showed dose-related increases in exposure, a mean half-life of roughly 21-32 hours, drug accumulation on repeated dosing (accumulation index 3.76-4.33), and only a minor food effect on peak concentration. MN-08 was well tolerated across the dose range studied, with all adverse events mild to moderate and no drug-related serious events. These favorable pharmacokinetic and safety findings support advancing MN-08 into Phase II trials for pulmonary arterial hypertension in Chinese patients.
Author(s): Yang E, Chen M, Wu M, Dong Q, Li J, Xu H, Qu B, Zhang H, Jin Z, Li G, Jing M, Zhang Z, Zhang G, Piao H
Published: February 25, 2026
Phoenix WinNonlin: From First-in-Human to Multiple Doses
Phoenix WinNonlin derived the pharmacokinetics behind this MN-08 Phase I study, spanning single ascending dose, multiple ascending dose, and food-effect designs in one program. Phoenix WinNonlin is the gold standard engine for noncompartmental analysis, PK/PD, and toxicokinetic modeling, part of a Phoenix platform built on more than 30 years of PK/PD expertise.
