Pharmacokinetics, Safety and Tolerability of HPP737, a Novel PDE4 Inhibitor, in Healthy Chinese Participants: Phase I Study.

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 Tmax 11-15 h) and a long elimination half-life (~21.2 h), supporting once-daily dosing. The increase in Cmax and AUC0-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.