PII-114 - EVALUATION OF HIGH-DOSE VUTIGLABRIDIN IN HEALTHY PARTICIPANTS: SAFETY, FOOD EFFECT, AND PHARMACOKINETICS AFTER SINGLE AND MULTIPLE ORAL ADMINISTRATIONS

S. Lee¹, H. Kim¹, S. Park¹, J. Chung², S. Loh³, S. Yoo³, K. Yu¹; ¹Seoul National University Hospital, ²Seoul National University Bundang Hospital, ³Glaceum Inc..

Background: Vutiglabridin, a synthetic glabridin derivative, is under clinical development as an obesity treatment that promotes lipolysis in adipose tissues and increases energy expenditure. This study aimed to evaluate the safety and pharmacokinetics (PKs) following single- and multiple-dose of vutiglabridin at doses greater than 720 mg, the highest dose in previous trials. We also evaluated the effect of food in the single-dose study.

Methods: The single-dose study was designed as a randomized, open-label, 2 x 2 crossover study with a 21-day washout between the two periods. Twelve participants were randomized 1:1 to one of two sequences (fasted to fed state, or vice versa) and received a single dose of vutiglabridin 1200 mg in each period. The multiple-dose study was conducted in a randomized, double-blind, placebo-controlled design. Participants in each dose group (800 or 1200 mg, n=8 each) were randomized to receive vutiglabridin or placebo in a 6:2 ratio once daily for 14 days in the fed state. Safety was assessed throughout the study. Serial blood samples for PK assessment were collected up to 192 hours in the single-dose study and 24 and 192 hours after the first and last doses, respectively, in the multiple-dose study. PK parameters were determined by non-compartmental analysis.

Results: A total of 12 and 16 participants completed the single- and multiple-dose studies, respectively. Nine adverse drug reactions (ADRs) occurred in 3 participants; the most common ADRs were headache and dizziness. All ADRs were mild in severity and resolved. In the single-dose study, the area under the plasma concentration‐time curve (AUClast) and the maximum concentration (Cmax) of vutiglabridin were 5.17- and 5.90-fold higher, respectively, in the fed than in the fasted state. The median time to Cmax (Tmax) was delayed from 2 hours in the fasted state to 3 hours in the fed state. In the multiple-dose study, the mean ± standard deviation values of the accumulation ratio of vutiglabridin systemic exposure were 8.28 ± 2.10 and 6.28 ± 1.92 in the 800 mg and 1200 mg dose groups, respectively.

Conclusion: Multiple oral administrations of vutiglabridin up to 1200 mg were safe and well-tolerated. This supports further clinical evaluations at higher exposure levels than before, and provides information for designing other clinical pharmacology studies with vutiglabridin.