Effects of Berberine Ursodeoxycholate (HTD1801) Versus Dapagliflozin in Patients With Type 2 Diabetes Inadequately Controlled With Metformin

A Phase 3, Multicenter, Randomized, Double-Blind, Active-Controlled (Dapagliflozin), Parallel Group Efficacy and Safety Study of HTD1801 in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin Alone

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

Study Overview

• Status: Recruiting
• Conditions: T2DM (Type 2 Diabetes Mellitus)
• Intervention / Treatment: Drug: HTD1801; Drug: Dapagliflozin

Detailed Description

This Phase 3 randomized, double-blind, active-controlled, parallel-group study will evaluate the efficacy and safety of HTD1801 compared to dapagliflozin after 24 weeks of treatment. All patients will remain on a stable dose of metformin throughout the study.

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 then be randomized 1:1 to receive HTD1801 1000 mg BID or dapagliflozin 10 mg QD.

• Study Type: Interventional
• Enrollment (Estimated): 418
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yi Huang; Phone Number: 86 13512789816; Email: huangyi@hightidetx.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University People's Hospital
  • Beijing, China
    • Recruiting
    • Beijing Pinggu Hospital
  • Binzhou, China
    • Recruiting
    • Binzhou Medical University Hospital
  • Changchun, China
    • Recruiting
    • The Second Norman Bethune Hospital of Jilin University
  • Changchun, China
    • Recruiting
    • Jilin Province FAW General Hospital
  • Changde, China
    • Recruiting
    • The First People's Hospital of Changde City
  • Changsha, China
    • Recruiting
    • The Third Xiangya Hospital of Central South University
  • Changsha, China
    • Recruiting
    • The First Hospital of Changsha
  • Changsha, China
    • Recruiting
    • The Second Xiangya Hospital of Central South University
  • Changsha, China
    • Recruiting
    • The Fourth Hospital of Changsha
  • Chongqing, China
    • Recruiting
    • Bishan Hospital of Chongqing
  • Deyang, China
    • Recruiting
    • Deyang People's Hospital
  • Handan, China
    • Recruiting
    • Handan First Hospital
  • Harbin, China
    • Recruiting
    • The Fourth Affiliated Hospital of Harbin Medical University
  • Huai'an, China
    • Recruiting
    • Huai'an Second People's Hospital
  • Huanggang, China
    • Recruiting
    • Huanggang Central Hospital
  • Huangshi, China
    • Recruiting
    • Huangshi Central Hospital
  • Huizhou, China
    • Recruiting
    • Huizhou Municipal Central Hospital
  • Huzhou, China
    • Recruiting
    • Huzhou central hospital
  • Jincheng, China
    • Recruiting
    • Jincheng General Hospital
  • Langfang, China
    • Recruiting
    • Hebei Petro China Center Hospital
  • Lianyungang, China
    • Recruiting
    • The Second People's Hospital of Lianyungang
  • Liaocheng, China
    • Recruiting
    • Liaocheng People's Hospital
  • Luoyang, China
    • Recruiting
    • Luoyang Third People's Hospital
  • Luoyang, China
    • Recruiting
    • The First Affiliated Hospital of Henan University of Science and Technology (Jinghua)
  • Luoyang, China
    • Recruiting
    • The First Affiliated Hospital of Henan University of Science and Technology (Kaiyuan)
  • Nanchang, China
    • Recruiting
    • The First Affiliated Hospital of Nanchang University
  • Nanchang, China
    • Recruiting
    • The Second Affiliated Hospital of Nanchang University
  • Nanjing, China
    • Recruiting
    • The Second Affiliated Hospital of Nanjing Medical University
  • Nanjing, China
    • Recruiting
    • Nanjing Drum Tower Hospital - The Affiliated Hospital of Nanjing University Medical School
  • Nantong, China
    • Recruiting
    • Affiliated Hospital of Nantong University
  • Nanyang, China
    • Recruiting
    • The First Affiliated Hospital of Nanyang Medical College
  • Panjin, China
    • Recruiting
    • Panjin Liaohe Oilfield Gem Flower Hospital
  • Pingxiang, China
    • Recruiting
    • Pingxiang People's Hospital
  • Qiqihar, China
    • Recruiting
    • The First Hospital of Qiqihar
  • Sanmenxia, China
    • Recruiting
    • Sanmenxia Central Hospital
  • Shanghai, China
    • Recruiting
    • Shanghai Sixth People's Hospital
  • Shanghai, China
    • Recruiting
    • Huadong Hospital
  • Shenyang, China
    • Recruiting
    • Shengjing Hospital of China Medical University
  • Shenyang, China
    • Recruiting
    • The People's Hospital of Liaoning Province
  • Wuhan, China
    • Recruiting
    • Wuhan Third Hospital
  • Xi'an, China
    • Recruiting
    • The Second Affiliated Hospital of Xi'an Jiaotong University
  • Xi'an, China
    • Recruiting
    • The First Affiliated Hospital of Xi'an Jiaotong Univerity
  • Xiangtan, China
    • Recruiting
    • The First People's Hospital of Xiangtan City
  • Xiangtan, China
    • Recruiting
    • Xiangtan Central Hospital
  • Xianyang, China
    • Recruiting
    • Xianyang Hospital of Yan'an University
  • Xuzhou, China
    • Recruiting
    • Xuzhou Cancer Hospital
  • Yibin, China
    • Recruiting
    • The Second People's Hospital of Yibin
  • Yiyang, China
    • Recruiting
    • Yiyang Central Hospital
  • Yueyang, China
    • Recruiting
    • Yueyang People's Hospital
  • Zaozhuang, China
    • Recruiting
    • Shandong Healthcare Group Zaozhuang Central Hospital
  • Zhengzhou, China
    • Recruiting
    • The Second Affiliated Hospital of Zhengzhou
  • Zhenjiang, China
    • Recruiting
    • Affiliated Hospital of Jiangsu University
  • Zhumadian, China
    • Recruiting
    • Zhumadian Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have been diagnosed with type 2 diabetes
• Have received a stable dose of metformin monotherapy for at least 8 weeks prior to screening
• If used any glucose-lowering drugs other than metformin within the 8 weeks prior to screening such use was ≤7 days and was discontinued at least 4 weeks prior to screening
• Have HbA1c ≥7.5% to ≤11.0% (screening) and HbA1c ≥7.0% to ≤10.5% (pre-randomization)
• Have fasting plasma glucose ≤13.9 mmol/L (screening and pre-randomization)
• Have a body mass index ≥19.0 kg/m^2 and ≤35.0 kg/m^2

Exclusion Criteria:

• Have type 1 diabetes
• Have had any acute diabetic complications within 12 months prior to screening
• Have had any Grade 3 hypoglycemic event within 12 months prior to screening
• Have had proliferative retinopathy or macular degeneration, severe diabetic neuropathy, or diabetic foot
• 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 12 weeks prior to screening
• Have used insulin or an insulin analogue for more than 14 days within 12 months prior to screening
• Have used any hypoglycemic drug other than metformin during the 4-week run-in period prior to randomization
• Have had weight gain or loss ≥5% during the 4-week run-in period prior to randomization
• Have a history of refractory or recurrent urinary tract infections or genital infections

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HTD1801; Administered orally twice daily (BID)	Drug: HTD1801; HTD1801 1000 mg BID administered orally BID as four capsules; Other Names: Berberine Ursodeoxycholate
Active Comparator: Dapagliflozin; Administered orally once daily (QD)	Drug: Dapagliflozin; Dapagliflozin 10 mg tablet administered orally QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Endpoint: Mean change in HbA1c	Mean change in HbA1c from baseline to Week 24	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Fasting Plasma Glucose	Mean change in fasting plasma glucose from baseline to Week 24	24 Weeks
Mean Change in 2-Hour Postprandial Glucose	Mean change in 2-hour postprandial glucose from baseline to Week 24	24 Weeks
Proportion of Patients Achieving HbA1c <7.0%	Proportion of patients achieving HbA1c <7.0% after 24 weeks of treatment	24 Weeks
Proportion of Patients Achieving HbA1c <6.5%	Proportion of patients achieving HbA1c <6.5% after 24 weeks of treatment	24 Weeks
Mean Change in Insulin Sensitivity (HOMA-IR)	Mean change in homeostatic model assessment for insulin resistance (HOMA-IR) from baseline to Week 24	24 Weeks
Mean Change in Low-Density Lipoprotein Cholesterol (LDL-C)	Mean change in LDL-C from baseline to Week 24	24 Weeks

Collaborators and Investigators

• Sponsor: HighTide Biopharma Pty Ltd
• Collaborators: Shenzhen HighTide Biopharmaceutical Ltd.
• Investigators: Study Director: Kui Liu, MD, Shenzhen HighTide Biopharmaceutical Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: May 10, 2024
• First Submitted That Met QC Criteria: May 10, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: HTD1801.PCT109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No