A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics of BGT-002, a Novel ATP-Citrate Lyase Inhibitor, in Healthy Chinese Subjects

Objective: This Phase I study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BGT-002, a novel ATP-citrate lyase (ACLY) inhibitor, in healthy Chinese adults. Methods: This study included three parts: Part I (single-ascending-dose study), Part II (multiple-ascending-dose study), and Part III (food effect study). A total of 104 healthy subjects were enrolled in the study and were given BGT-002 tablet or placebo per protocol requirements. Blood samples were collected for pharmacokinetic and pharmacodynamic analysis. Safety was assessed by clinical examinations and adverse events. Results: In Part I, BGT-002 demonstrated rapid absorption with a Tmax of 0.67 to 1.75 hours, and slow elimination with a T1/2 of 24.53 to 72.86 hours, prolonged with increased dosages. Cmax and AUC0-infinity ranged from 1.55 to 48.39 mu g/mL, and 31.09 to 2930.69 h<middle dot>mu g/mL, respectively. In Part II, the accumulation index (Rac) of Cmax and AUCtau following 14 days of consecutive administration were 3.53 to 3.62 and 5.29 to 5.59, respectively, with a dose-proportionality PK profile. The levels of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), and low-density lipoprotein cholesterol (LDL-C) were maximally decreased by 15.80%, 18.50%, and 22.37%, respectively. In Part III, the geometric mean ratio (90% CI) of fed to fasting condition in Cmax and AUC0-infinity of BGT-002 were 73.11% and 98.36%, respectively, indicating a minor food effect on the absorption rate. Across the study, two cases of Grade 3 adverse events (elevated blood triglycerides) were reported, both of which were assessed as not related to BGT-002. No serious adverse events were observed. Conclusion: BGT-002 demonstrated favorable safety, tolerability, and lipid-lowering effects, supporting its potential for further clinical development.