PII-018 - THE PHARMACODYNAMICS, PHARMACOKINETICS, AND SAFETY OF VUTIGLABRIDIN, A SYNTHETIC GLABRIDIN DERIVATIVE, AFTER MULTIPLE ADMINISTRATION IN OBESE SUBJECTS.

H. Kim¹, J. Oh², S. Seong³, Y. Yoon³, S. Yoo⁴, S. Lee⁴, Y. Kim⁴, K. Yu¹; ¹Seoul National University Bundang Hospital, Seoul, Republic of Korea, ²Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea, ³Kyungpook National University Hospital, Daegu, Republic of Korea, ⁴Glaceum Inc., Gyeonggi-do, Republic of Korea.

Background: Vutiglabridin is under clinical development as an obesity treatment that promotes lipolysis in adipose tissues by improving inflammation-related indicators in immune cells. This study aimed to evaluate the pharmacodynamics, pharmacokinetics (PKs), and safety of vutiglabridin after multiple administration in obese subjects.

Methods: A dose-block randomized, double-blind, placebo-controlled, multiple dose study was conducted in obese subjects with a body mass index of 30 kg/m2 or greater. Subjects in each dose group (480 mg or 720 mg; n=10, each) randomly received vutiglabridin or placebo once daily for 14 days under fed conditions at a ratio of 8:2. Body weight and waist circumference were evaluated up to 21 days after the first dose. Serial blood samples for PK assessment were collected after the first and last dose. Safety profiles were assessed throughout the study.

Results: A total of 9 and 10 subjects completed the study in the 480 mg and 720 mg dose groups, respectively. After treatment of the study drug for 14 days, the mean ± standard deviation values of changes from baseline for body weight were -1.81 ± 1.93 kg in the 480 mg dose group, -1.08 ± 1.20 kg in the 720 mg dose group, and -0.90 ± 1.67 kg in the placebo group. The corresponding values for waist circumference were -1.20 ± 1.89 cm, -1.39 ± 2.08 cm, and 0.30 ± 1.78 cm. At steady-state, the maximum concentration of vutiglabridin was approximately 10% higher in obese subjects than in healthy subjects, but the area under the time-concentration curve within the dosing interval was approximately 20% lower. Multiple doses of vutiglabridin were well tolerated up to 720 mg.

Conclusion: Vutiglabridin was well tolerated and induced reduction of body weight and waist circumference in obese subjects. This supports further clinical trials with longer-term administrations in obese patients.