Efficacy and Safety of Berberine Ursodeoxycholate (HTD1801) in Patients With Type 2 Diabetes Inadequately Controlled With Metformin

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study Evaluating the Efficacy and Safety of HTD1801 in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin

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

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: HTD1801; Drug: Placebo

Detailed Description

This Phase 3, randomized, double-blind, placebo-controlled study will evaluate the safety and efficacy of HTD1801 in two phases, a 24-week double-blind phase followed by a 28-week open-label extension. 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 modifications, concomitant medications, and procedures for self-monitoring of blood glucose. Following this period, patient eligibility will be reassessed. Eligible patients will then be randomized 2:1 to receive HTD1801 1000 mg twice daily (BID) or placebo for 24 weeks.

Patients who complete the double-blind treatment phase will enter an open-label extension period where all patients will receive HTD1801 1000 mg BID for 28 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 555
• Phase: Phase 3

Contacts and Locations

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

Study Locations

• China
  • Baotou, China
    • Recruiting
    • Baogang Hospital of Inner Mongolia
    • Principal Investigator: Ziling Li
  • Beijing, China
    • Recruiting
    • Peking University People's Hospital
    • Principal Investigator: Linong Ji
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Principal Investigator: Weigang Zhao
  • Beijing, China
    • Recruiting
    • Beijing Friendship Hospital, Capital Medical University
    • Principal Investigator: Mingxia Yuan
  • Beijing, China
    • Recruiting
    • Beijing Luhe Hospital Capital Medical University
    • Principal Investigator: Dong Zhao
  • Beijing, China
    • Recruiting
    • Beijing Pinggu Hospital
    • Principal Investigator: yufeng li
  • Changchun, China
    • Recruiting
    • The Second Norman Bethune Hospital of Jilin University
    • Principal Investigator: Hanqing Cai
  • Changde, China
    • Recruiting
    • The First People's Hospital of Changde City
    • Principal Investigator: Shenglian Gan
  • Changsha, China
    • Recruiting
    • The Third Xiangya Hospital of Central South University
    • Principal Investigator: Ping Jin
  • Changsha, China
    • Recruiting
    • Hunan Provincial People's Hospital
    • Principal Investigator: Chi Zhang
  • Chongqing, China
    • Recruiting
    • Chongqing University Three Gorges Hospital
    • Principal Investigator: Lian Guo
  • Datong, China
    • Recruiting
    • The Third People's Hospital of Datong
    • Principal Investigator: Yan Liu
  • Guangzhou, China
    • Recruiting
    • Nanfang Hospital, Southern Medical University
    • Principal Investigator: Yaoming Xue
  • Handan, China
    • Recruiting
    • Handan First Hospital
    • Principal Investigator: Haifang Wang
  • Harbin, China
    • Recruiting
    • The Fourth Affiliated Hospital of Harbin Medical University
    • Principal Investigator: ZhiFeng Cheng
  • Hefei, China
    • Recruiting
    • Anhui Provincial Hospital
    • Principal Investigator: Shandong Ye
  • Hefei, China
    • Recruiting
    • The Second Hospital of Anhui Medical University
    • Principal Investigator: Tianrong Pan
  • Hengshui, China
    • Recruiting
    • Hengshui People's Hospital (Harrison International Peace Hospital)
    • Principal Investigator: Jianlin Geng
  • Heze, China
    • Recruiting
    • Heze Municipal Hospital
    • Principal Investigator: Mingming Yang
  • Huai'an, China
    • Recruiting
    • Huai'an First People's Hospital
    • Principal Investigator: Li Mao
  • Huangshi, China
    • Recruiting
    • Huangshi Central Hospital
    • Principal Investigator: Xiaowen Chen
  • Huizhou, China
    • Recruiting
    • Huizhou Municipal Central Hospital
    • Principal Investigator: Shu Li
  • Huzhou, China
    • Recruiting
    • Huzhou Central Hospital
    • Principal Investigator: Jianping Yao
  • Jinan, China
    • Recruiting
    • Jinan Central Hospital
    • Principal Investigator: Xiaolin Dong
  • Jingzhou, China
    • Recruiting
    • Jingzhou Central Hospital
    • Principal Investigator: Junli Xue
  • Jinzhou, China
    • Recruiting
    • Jinzhou Central Hospital
    • Principal Investigator: Xueying Wang
  • Kashgar, China
    • Recruiting
    • The First People's Hospital of Kashgar
    • Principal Investigator: Adilijiang Abulimiti
  • Langfang, China
    • Recruiting
    • Hebei Petro China Center Hospital
    • Principal Investigator: Jie Han
  • Liaocheng, China
    • Recruiting
    • Liaocheng People's Hospital
    • Principal Investigator: Jie Bai
  • Luoyang, China
    • Recruiting
    • The First Affiliated Hospital of Henan University of Science and Technology (Jinghua)
    • Principal Investigator: Liujun Fu
  • Luoyang, China
    • Recruiting
    • The First Affiliated Hospital of Henan University of Science and Technology (Kaiyuan)
    • Principal Investigator: Yujin Ma
  • Nanjing, China
    • Recruiting
    • The Second Affiliated Hospital of Nanjing Medical University
    • Principal Investigator: Yibing Lu
  • Nanjing, China
    • Recruiting
    • Nanjing First Hospital
    • Principal Investigator: Jianhua Ma
  • Nanjing, China
    • Recruiting
    • Nanjing Drum Tower Hospital - The Affiliated Hospital of Nanjing University Medical School
    • Principal Investigator: Yan Bi
  • Nanjing, China
    • Recruiting
    • Nanjing Jiangning Hospital
    • Principal Investigator: Kun Wang
  • Nanjing, China
    • Recruiting
    • Sir Run Run Hospital Nanjing Medical University
    • Principal Investigator: Yu Liu
  • Nanning, China
    • Recruiting
    • The First People's Hospital of Nanning
    • Principal Investigator: Yuanyuan Lin
  • Nanyang, China
    • Recruiting
    • The First Affiliated Hospital of Nanyang Medical College
    • Principal Investigator: Dexue Liu
  • Panjin, China
    • Recruiting
    • Panjin Liaohe Oilfield Gem Flower Hospital
    • Principal Investigator: Xin Zhang
  • Qiqihar, China
    • Recruiting
    • The First Hospital of Qiqihar
    • Principal Investigator: Yang Lin
  • Shanghai, China
    • Recruiting
    • Shanghai East Hospital of Tongji University
    • Principal Investigator: Bo Feng
  • Shanghai, China
    • Recruiting
    • Shanghai Pudong New Area People's Hospital
    • Principal Investigator: Ying Wang
  • Shenyang, China
    • Recruiting
    • Shengjing Hospital of China Medical University
    • Principal Investigator: Xiaoguang Shi
  • Shenyang, China
    • Recruiting
    • The Sixth People's Hospital of Shenyang
    • Principal Investigator: Xiaomei Wang
  • Shenzhen, China
    • Recruiting
    • Shenzhen People's Hospital
    • Principal Investigator: Yan Wu
  • Shenzhen, China
    • Recruiting
    • The University of Hong Kong - Shenzhen Hospital
    • Principal Investigator: Wei Liang
  • Shiyan, China
    • Recruiting
    • Taihe Hospital
    • Principal Investigator: Xuefeng Li
  • Siping, China
    • Recruiting
    • Siping City Central People's Hospital
    • Principal Investigator: Li Sun
  • Suzhou, China
    • Recruiting
    • The first affiliated hospital of suzhou University
    • Principal Investigator: Bimin Shu
  • Tianjin, China
    • Recruiting
    • People's Hospital of Tianjin
    • Principal Investigator: Jingna Lin
  • Tonghua, China
    • Recruiting
    • Tonghua Central Hospital
    • Principal Investigator: Shuping Zhao
  • Wuhan, China
    • Recruiting
    • The Central Hospital of Wuhan
    • Principal Investigator: Zhongjing Wang
  • Wuhu, China
    • Recruiting
    • Yijishan Hospital of Wannan Medical College
    • Principal Investigator: Jialin Gao
  • Xiangtan, China
    • Recruiting
    • The First People's Hospital of Xiangtan City
    • Principal Investigator: Genqing Xie
  • Xuzhou, China
    • Recruiting
    • The Affiliated Hospital Of Xuzhou Medical University
    • Principal Investigator: Juan Sun
  • Yanan, China
    • Recruiting
    • Yanan University Affiliated Hospital
    • Principal Investigator: Sheli Li
  • Yueyang, China
    • Recruiting
    • Yueyang People's Hospital
    • Principal Investigator: Wenli Sun
  • Yuncheng, China
    • Recruiting
    • Yuncheng Central Hospital
    • Principal Investigator: Xiaojing Wang
  • Zhengzhou, China
    • Recruiting
    • The Second Affiliated Hospital of Zhengzhou University
    • Principal Investigator: Dongming Zhang
  • Zhenjiang, China
    • Recruiting
    • Affiliated Hospital of Jiangsu University
    • Principal Investigator: Guoyue Yuan
  • Zhumadian, China
    • Recruiting
    • Zhumadian Central Hospital
    • Principal Investigator: Lianwei Wang
  • Zhuzhou, China
    • Recruiting
    • ZhuZhou Central Hospital
    • Principal Investigator: Lihua Zhou
  • Zibo, China
    • Recruiting
    • Zibo central Hospital
    • Principal Investigator: Xiaodong Zhao
  • Zunyi, China
    • Recruiting
    • The First People's Hospital of Zunyi
    • Principal Investigator: Chengyan Jiang

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
• 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 to ≤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

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 administered orally BID as four capsules; Other Names: berberine ursodeoxycholate
Placebo Comparator: Placebo; Administered orally BID	Drug: Placebo; Matching placebo administered orally BID as four capsules

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
Double-blind (DB) Phase: mean change in fasting plasma glucose	Mean change in fasting plasma glucose from baseline to Week 24	24 Weeks
DB Phase: mean change in 2-hour postprandial glucose	Mean change in 2-hour postprandial glucose from baseline to Week 24	24 Weeks
DB Phase: proportion of patients achieving HbA1c <7.0%	Proportion of patients achieving HbA1c target value of <7.0% at Week 24	24 Weeks
DB Phase: proportion of patients achieving HbA1c <6.5%	Proportion of patients achieving HbA1c target value of <6.5% at Week 24	24 Weeks
DB Phase: 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
DB Phase: mean change in low-density lipoprotein cholesterol (LDL-C)	Mean change in LDL-C from baseline to Week 24	24 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Open-Label Extension (OLE) Phase: mean change in HbA1c	Mean change HbA1c from baseline to Week 52	52 Weeks
OLE Phase: mean change in 2-Hour postprandial glucose	Mean change in 2-Hour postprandial glucose from baseline to Week 52	52 Weeks
OLE Phase: proportion of patients achieving HbA1c <7.0%	Proportion of patients achieving HbA1c target value of <7.0% at Week 52	52 Weeks
OLE Phase: proportion of patients achieving HbA1c <6.5%	Proportion of patients achieving HbA1c target value of <6.5% at Week 52	52 Weeks
OLE Phase: mean change in insulin sensitivity (HOMA-IR)	Mean change in HOMA-IR from baseline to Week 52	52 Weeks
OLE Phase: mean change in LDL-C	Mean change in LDL-C from baseline to Week 52	52 Weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: April 3, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 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; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid
• Other Study ID Numbers: HTD1801.PCT106

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