Efficacy and Safety of Berberine Ursodeoxycholate (HTD1801) in Patients With Type 2 Diabetes (SYMPHONY-1)

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Study Evaluating the Efficacy and Safety of HTD1801 in Patients With Type 2 Diabetes Mellitus Who Have Poor Glycemic Control After Dietary and Exercise Interventions

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 diet and exercise alone.

Study Overview

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

Detailed Description

This Phase 3 randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety 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 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 2:1 to receive HTD1801 1000 mg twice daily (BID) or placebo for 24 weeks.

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

• Study Type: Interventional
• Enrollment (Actual): 408
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Xuancheng, Anhui, China
      • Xuancheng People's Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Peking University People's Hospital
    • Beijing, Beijing Municipality, China
      • Peking Union Medical College Hospital
    • Beijing, Beijing Municipality, China
      • Beijing Pinggu Hospital
    • Beijing, Beijing Municipality, China
      • Fuwai Hospital, CAMS & PUMC
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China
      • Chongqing University Three Gorges Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Nanfang Hospital, Southern Medical University
    • Huizhou, Guangdong, China
      • Huizhou Municipal Central Hospital
    • Shenzhen, Guangdong, China
      • ShenZhen People's Hospital
  • Guangxi
    • Liuchow, Guangxi, China
      • Liuzhou people's Hospital
  • Hebei
    • Cangzhou, Hebei, China
      • Cangzhou Central Hospital
    • Handan, Hebei, China
      • Handan First Hospital
    • Hengshui, Hebei, China
      • Hengshui People's Hospital (Harrison International Peace Hospital)
    • Langfang, Hebei, China
      • Hebei Petro China Central Hospital
    • Shijiazhuang, Hebei, China
      • The First Hospital of Hebei Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • The Fourth Affiliated Hospital of Harbin Medical University
    • Qiqihar, Heilongjiang, China
      • The Third Affiliated Hospital of Qiqihar Medical University
    • Qiqihar, Heilongjiang, China
      • The First Hospital of Qiqihar
  • Henan
    • Luoyang, Henan, China
      • The First Affiliated Hospital of Henan University of Science & Technology (Jinghua)
    • Luoyang, Henan, China
      • The First Affiliated Hospital of Henan University of Science & Technology (Kaiyuan)
    • Nanyang, Henan, China
      • The First Affiliated Hospital of Nanyang Medical College
    • Zhumadian, Henan, China
      • Zhumadian Central Hospital
  • Hubei
    • Huangshi, Hubei, China
      • Huangshi Central Hospital
    • Jingzhou, Hubei, China
      • Jingzhou Central Hospital
    • Wuhan, Hubei, China
      • The Central Hospital of Wuhan
  • Hunan
    • Changde, Hunan, China
      • The First People's Hospital of Changde City
    • Changsha, Hunan, China
      • Hunan Provincial People's Hospital
    • Yueyang, Hunan, China
      • Yueyang People's Hospital
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • Baotou City Central Hospital
    • Hohhot, Inner Mongolia, China
      • Inner Mongolia People's Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China
      • The First People's Hospital of Changzhou
    • Huai'an, Jiangsu, China
      • Huai'an First People's Hospital
    • Lianyungang, Jiangsu, China
      • The Second People's Hospital of Lianyungang
    • Nanjing, Jiangsu, China
      • Nanjing First Hospital
    • Nanjing, Jiangsu, China
      • Nanjing Jiangning Hospital
    • Nanjing, Jiangsu, China
      • The Second Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China
      • Nanjing Drum Tower Hospital - The Affiliated Hospital of Nanjing University Medical School
    • Nanjing, Jiangsu, China
      • Sir Run Run Shaw Hospital Nanjing Medical University
    • Xuzhou, Jiangsu, China
      • The Affiliated Hospital of Xuzhou Medical University
    • Zhenjiang, Jiangsu, China
      • Affiliated Hospital of Jiangsu University
  • Jiangxi
    • Pingxiang, Jiangxi, China
      • Pingxiang People's Hospital
  • Jilin
    • Changchun, Jilin, China
      • The Second Hospital of Jilin University
    • Tonghua, Jilin, China
      • Tonghua Central Hospital
  • Liaoning
    • Panjin, Liaoning, China
      • Panjin Liaohe Oilfield GEM Flower Hospital
    • Shenyang, Liaoning, China
      • The Sixth People's Hospital of Shenyang
  • Qinghai
    • Xining, Qinghai, China
      • Qinghai Provincial People's Hospital
  • Shaanxi
    • Xianyang, Shaanxi, China
      • The Second Affiliated Hospital of Shaanxi University of Chinese Medicine
  • Shandong
    • Jinan, Shandong, China
      • Jinan Central Hospital
    • Liaocheng, Shandong, China
      • Liaocheng People's Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Shanghai East Hospital of Tongji University
  • Shanxi
    • Datong, Shanxi, China
      • The Third People's Hospital of Datong
    • Yuncheng, Shanxi, China
      • Yuncheng Central Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • People's Hospital of Tianjin
  • Xinjiang
    • Kashgar, Xinjiang, China
      • The First People's Hospital of Kashi
  • Yunnan
    • Kunming, Yunnan, China
      • The Second Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Huzhou, Zhejiang, China
      • Huzhou Central Hospital

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Have been diagnosed with Type 2 diabetes mellitus
• Have followed dietary and exercise interventions for at least 8 weeks prior to screening
• If used any glucose-lowering drugs 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 ≥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

Key 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 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 values of <7.0% at Week 24	24 Weeks
DB Phase: Proportion of patients achieving HbA1c <6.5%	Proportion of patients achieving HbA1c target values 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 in 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 values of <7.0% at Week 52	52 Weeks
OLE Phase: Proportion of patients achieving HbA1c <6.5%	Proportion of patients achieving HbA1c target values 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
• Collaborators: Shenzhen HighTide Biopharmaceutical Ltd.
• Investigators: Study Director: Kui Liu, MD, Shenzhen HighTide Biopharmaceutical Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2023
• Primary Completion (Actual): December 12, 2024
• Study Completion (Actual): August 4, 2025

Study Registration Dates

• First Submitted: March 27, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 25, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid
• Other Study ID Numbers: HTD1801.PCT105

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
• product manufactured in and exported from the U.S.: No