A Phase 2 Study of Berberine Ursodeoxycholate (HTD1801) in Patients With Type 2 Diabetes Inadequately Controlled With Diet and Exercise

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Evaluate the Efficacy and Safety of HTD1801 in Patients With Type 2 Diabetes Mellitus (T2DM) Inadequately Controlled With Diet and Exercise

The goal of this clinical trial is to evaluate the efficacy and safety of berberine ursodeoxycholate (HTD1801) compared to placebo in patients with type 2 diabetes inadequately controlled with diet and exercise alone.

This Phase 2 randomized, double-blind, placebo-controlled trial will evaluate the efficacy and safety of HTD1801 compared to placebo after 12-weeks of treatment.

To ensure stabilization of glycemic control, eligible patients will first participate in a 4-week single-blind run-in period where investigators will provide guidance on lifestyle modification, concomitant medications, and procedures for self-monitoring of blood glucose. Following this period, patient eligibility will be reassessed. Eligible patients will be randomized 1:1:1 to receive HTD1801 500 mg twice daily (BID), HTD1801 1000 mg BID, or placebo BID.

Key Inclusion Criteria:

• Have been diagnosed with type 2 diabetes mellitus according to the 1999 World Health Organization (WHO) criteria
• Have followed dietary and exercise interventions for at least 8 weeks prior to screening
• Have HbA1c ≥7.5% to ≤11.0% (screening) and ≥7.0% to ≤10.5% (pre-randomization)
• Have fasting plasma glucose <13.9 mmol/L (screening and pre-randomization)
• Have a body mass index ≥18 kg/m^2 to ≤40 kg/m^2

Key Exclusion Criteria:

• Have type 1 diabetes mellitus or specific type of diabetes mellitus (pancreatic injury-induced diabetes mellitus, diabetes mellitus caused by Cushing's syndrome or acromegaly, etc.)
• Have had diabetic ketoacidosis or hyperglycemic hyperosmolar state within 6 months prior to screening
• Have had 2 or more Grade 3 hypoglycemic events within 12 months prior to screening
• Have unstable or treatment-requiring proliferative retinopathy or macular degeneration, severe diabetic neuropathy, diabetic foot, or intermittent claudication within 6 months prior to screening
• Have been taking any weight loss medication or dietary supplement, have participated in a weight loss program, or have adhered to a special diet within 4 weeks prior to screening
• Have continuously used insulin or an insulin analogue for more than 14 days within 12 months prior to screening
• Have used 2 or more classes of hypoglycemic medications for more than 8 weeks within 12 months prior to screening
• Have used any glucose-modifying medications within 8 weeks prior to screening
• Have had weight gain or loss ≥5% from screening to randomization