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

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