2001-LB: Symphony 1—A Randomized, Placebo-Controlled Phase 3 Study of Berberine Ursodeoxycholate as Monotherapy in Patients with Type 2 Diabetes

Introduction and Objective: HTD1801 is a gut liver anti-inflammatory metabolic modulator that activates AMPK and inhibits the NLRP3 inflammasome. The objective of this study was to evaluate the efficacy and safety of HTD1801 compared to placebo in patients with T2D inadequately controlled with diet and exercise alone. Methods: This Phase 3 randomized, double-blind, placebo-controlled study was conducted at 56 sites in China (NCT06350890). Following a 4-week run-in period, eligible patients with T2D and HbA1c between 7.0%-10.5% were randomized 2:1 to HTD1801 1000 mg BID (N=271) or placebo (N=136). The primary endpoint was the change from baseline in HbA1c at Week 24. Results: Baseline characteristics were balanced across groups. The primary endpoint was achieved at Week 24, HTD1801 treated patients achieved an LS mean change in HbA1c of -1.26% compared to -0.61% with placebo (LS mean diff: -0.65, p<0.0001). Significant improvements were also observed in other key glycemic, lipid, and inflammatory parameters including, 2-hr PPG, FPG, LDL-c, and hs-CRP. Adverse events (AEs) occurred in 75% vs 67% of patients while serious AEs occurred in 3% vs 6% of patients with HTD1801 vs placebo, respectively. One HTD1801-treated patient experienced a mild AE of hypoglycemia. Conclusion: HTD1801 has been shown to be an effective monotherapy for T2D by improving glycemic/cardiometabolic control and was generally safe and well tolerated. Disclosure L. Ji: None. J. Ma: None. Z. Cheng: None. D. Liu: None. H. Cai: None. S. Wang: None. X. Wang: None. Y. Ma: None. X. Wang: None. J. Han: None. G. Yuan: None. Y. Zhang: None. F. Yu: None. K. Liu: Employee; HighTide Therapeutics, Inc. Stock/Shareholder; HighTide Therapeutics, Inc. M. Yu: Employee; HighTide Therapeutics, Inc. Stock/Shareholder; HighTide Therapeutics, Inc. L. Liu: Employee; HighTide Therapeutics, Inc. Stock/Shareholder; HighTide Therapeutics, Inc.