Pharmacokinetics, pharmacodynamics and safety of vutiglabridin after multiple oral administrations in healthy female and obese subjects.

Abstract

Aims: Vutiglabridin (HSG4112) is a novel drug under clinical development for antiobesity treatment. This study aimed to evaluate the pharmacokinetics (PKs) and safety of vutiglabridin after multiple oral administrations in healthy Korean female and obese subjects and explore short-term pharmacodynamic (PD) responses.

Methods: Two separate randomized, double-blind, placebo-controlled studies were conducted in healthy female and obese subjects. The subjects in each dose group (480 or 720 mg) received vutiglabridin or placebo once daily for 14 days under fed conditions at an 8:2 ratio. Serial blood samples were collected on days 1 and 14 for PK analysis. PD biomarkers related to obesity and inflammation were assessed, and safety and tolerability were evaluated throughout the study.

Results: At steady state, obese subjects exhibited a 9%-13% higher maximum concentration (C_max,ss) and a 17%-19% lower area under the plasma concentration-time curve for a dosing interval at steady state (AUC_τ,ss). This profile reflects altered absorption and distribution due to obesity-related physiological changes. After 14 days of treatment, compared with healthy females, obese subjects had greater decreases in baseline-corrected body weights in the 480 mg, 720 mg and placebo groups. Vutiglabridin was safe and well tolerated in both groups.

Conclusions: Vutiglabridin presented higher peak plasma concentrations but lower systemic exposure in obese subjects than in healthy females. Additionally, a modest downward trend in body weight was observed in obese subjects relative to healthy female subjects. These findings support further long-term phase II clinical trials.