Background and Objective: HPP737, a novel phosphodiesterase 4 (PDE4) inhibitor, was designed to treat chronic obstructive pulmonary disease (COPD). This study aimed to evaluate its pharmacokinetics, safety and tolerability in healthy Chinese participants. Methods: In this randomized, double-blind, placebo-controlled study, 72 healthy Chinese participants received single ascending doses (SAD: 6, 10, 20, 30 mg) or multiple ascending doses (MAD: 10, 20 mg once daily for 7 days) of HPP737 or placebo under a standardized high-fat breakfast. Primary endpoints included pharmacokinetic parameters and the incidence and severity of adverse events (AEs). Results: HPP737 exhibited slow absorption (median T max 11– 15 h) and a long elimination half-life (~21.2 h), supporting once-daily dosing. The increase in C max and AUC 0-t were slightly less than dose-proportional. Steady-state plasma concentrations were achieved within 3 days after once administration, with moderate accumulation (accumulation ratios: 1.4– 2.2). A distinctive dose-dependent reduction in serum uric acid (hypouricemia) was observed, which was asymptomatic and reversible. Treatment-emergent AEs were predominantly mild (Grade 1) and central nervous system (CNS) -related adverse reactions were notably infrequent; no serious AEs or deaths occurred. Conclusion: HPP737 showed a favorable pharmacokinetics profile suitable for once-daily administration and was well-tolerated in healthy Chinese participants, with a notably low incidence of CNS-related effects—a common limitation of existing PDE4 inhibitors. Collectively, these findings support the continued clinical development of HPP737 as a potential treatment for COPD. An infographic detailing a study on HPP737, a novel PDEi, involving 72 healthy Chinese participants in a randomized, double-blind trial. The study highlights the drug’s slow release and long-acting properties, with a time to peak of 11 to 15 hours and an elimination half-life of 21.2 hours, supporting once-daily dosing. The safety profile indicates no serious adverse events, lower central nervous system toxicity and dose-dependent hypouricemia. The study concludes with favorable pharmacokinetics and safety profile for further clinical development in chronic obstructive pulmonary disease.HPP737 study: 72 participants, slow release, safe, favorable pharmacokinetics. Keywords: PDE4 inhibitor, HPP737, pharmacokinetics, phase I clinical trial, healthy volunteers, tolerability
Ye et al. (Fri,) studied this question.