## Protocol Section
### Identification Module
**NCT ID:** NCT06415773

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

**Official Title:** 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

#### Organization Study ID Info
**ID:** HTD1801.PCT109
#### Organization
**Class:** INDUSTRY
**Full Name:** HighTide Biopharma Pty Ltd
### Status Module
#### Completion Date
**Date:** 2025-09

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-10

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-07

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05

**Type:** ESTIMATED

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-10
**Study First Submit QC Date:** 2024-05-10
### Sponsor Collaborators Module

#### Collaborators

**Class:** UNKNOWN

**Name:** Shenzhen HighTide Biopharmaceutical Ltd.

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** HighTide Biopharma Pty Ltd

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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.

**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.

### Conditions Module

**Conditions:**

- T2DM (Type 2 Diabetes Mellitus)

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** DOUBLE

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 418

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Administered orally twice daily (BID)

**Intervention Names:**

- Drug: HTD1801

**Label:** HTD1801

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Administered orally once daily (QD)

**Intervention Names:**

- Drug: Dapagliflozin

**Label:** Dapagliflozin

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- HTD1801

**Description:** HTD1801 1000 mg BID administered orally BID as four capsules

**Name:** HTD1801

**Other Names:**

- Berberine Ursodeoxycholate

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Dapagliflozin

**Description:** Dapagliflozin 10 mg tablet administered orally QD

**Name:** Dapagliflozin

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Mean change in HbA1c from baseline to Week 24

**Measure:** Primary Endpoint: Mean change in HbA1c

**Time Frame:** 24 Weeks

#### Secondary Outcomes

**Description:** Mean change in fasting plasma glucose from baseline to Week 24

**Measure:** Mean Change in Fasting Plasma Glucose

**Time Frame:** 24 Weeks

**Description:** Mean change in 2-hour postprandial glucose from baseline to Week 24

**Measure:** Mean Change in 2-Hour Postprandial Glucose

**Time Frame:** 24 Weeks

**Description:** Proportion of patients achieving HbA1c \<7.0% after 24 weeks of treatment

**Measure:** Proportion of Patients Achieving HbA1c <7.0%

**Time Frame:** 24 Weeks

**Description:** Proportion of patients achieving HbA1c \<6.5% after 24 weeks of treatment

**Measure:** Proportion of Patients Achieving HbA1c <6.5%

**Time Frame:** 24 Weeks

**Description:** Mean change in homeostatic model assessment for insulin resistance (HOMA-IR) from baseline to Week 24

**Measure:** Mean Change in Insulin Sensitivity (HOMA-IR)

**Time Frame:** 24 Weeks

**Description:** Mean change in LDL-C from baseline to Week 24

**Measure:** Mean Change in Low-Density Lipoprotein Cholesterol (LDL-C)

**Time Frame:** 24 Weeks

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** huangyi@hightidetx.com

**Name:** Yi Huang

**Phone:** 86 13512789816

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Beijing

**Country:** China

**Facility:** Beijing Pinggu Hospital

**Status:** RECRUITING

**Location 2:**

**City:** Beijing

**Country:** China

**Facility:** Peking University People's Hospital

**Status:** RECRUITING

**Location 3:**

**City:** Binzhou

**Country:** China

**Facility:** Binzhou Medical University Hospital

**Status:** RECRUITING

**Location 4:**

**City:** Changchun

**Country:** China

**Facility:** Jilin Province FAW General Hospital

**Status:** RECRUITING

**Location 5:**

**City:** Changchun

**Country:** China

**Facility:** The Second Norman Bethune Hospital of Jilin University

**Status:** RECRUITING

**Location 6:**

**City:** Changde

**Country:** China

**Facility:** The First People's Hospital of Changde City

**Status:** RECRUITING

**Location 7:**

**City:** Changsha

**Country:** China

**Facility:** The First Hospital of Changsha

**Status:** RECRUITING

**Location 8:**

**City:** Changsha

**Country:** China

**Facility:** The Fourth Hospital of Changsha

**Status:** RECRUITING

**Location 9:**

**City:** Changsha

**Country:** China

**Facility:** The Second Xiangya Hospital of Central South University

**Status:** RECRUITING

**Location 10:**

**City:** Changsha

**Country:** China

**Facility:** The Third Xiangya Hospital of Central South University

**Status:** RECRUITING

**Location 11:**

**City:** Chongqing

**Country:** China

**Facility:** Bishan Hospital of Chongqing

**Status:** RECRUITING

**Location 12:**

**City:** Deyang

**Country:** China

**Facility:** Deyang People's Hospital

**Status:** RECRUITING

**Location 13:**

**City:** Handan

**Country:** China

**Facility:** Handan First Hospital

**Status:** RECRUITING

**Location 14:**

**City:** Harbin

**Country:** China

**Facility:** The Fourth Affiliated Hospital of Harbin Medical University

**Status:** RECRUITING

**Location 15:**

**City:** Huai'an

**Country:** China

**Facility:** Huai'an Second People's Hospital

**Status:** RECRUITING

**Location 16:**

**City:** Huanggang

**Country:** China

**Facility:** Huanggang Central Hospital

**Status:** RECRUITING

**Location 17:**

**City:** Huangshi

**Country:** China

**Facility:** Huangshi Central Hospital

**Status:** RECRUITING

**Location 18:**

**City:** Huizhou

**Country:** China

**Facility:** Huizhou Municipal Central Hospital

**Status:** RECRUITING

**Location 19:**

**City:** Huzhou

**Country:** China

**Facility:** Huzhou Central Hospital

**Status:** RECRUITING

**Location 20:**

**City:** Jincheng

**Country:** China

**Facility:** Jincheng General Hospital

**Status:** RECRUITING

**Location 21:**

**City:** Langfang

**Country:** China

**Facility:** Hebei Petro China Center Hospital

**Status:** RECRUITING

**Location 22:**

**City:** Lianyungang

**Country:** China

**Facility:** The Second People's Hospital of Lianyungang

**Status:** RECRUITING

**Location 23:**

**City:** Liaocheng

**Country:** China

**Facility:** Liaocheng People's Hospital

**Status:** RECRUITING

**Location 24:**

**City:** Luoyang

**Country:** China

**Facility:** Luoyang Third People's Hospital

**Status:** RECRUITING

**Location 25:**

**City:** Luoyang

**Country:** China

**Facility:** The First Affiliated Hospital of Henan University of Science and Technology (Jinghua)

**Status:** RECRUITING

**Location 26:**

**City:** Luoyang

**Country:** China

**Facility:** The First Affiliated Hospital of Henan University of Science and Technology (Kaiyuan)

**Status:** RECRUITING

**Location 27:**

**City:** Nanchang

**Country:** China

**Facility:** The First Affiliated Hospital of Nanchang University

**Status:** RECRUITING

**Location 28:**

**City:** Nanchang

**Country:** China

**Facility:** The Second Affiliated Hospital of Nanchang University

**Status:** RECRUITING

**Location 29:**

**City:** Nanjing

**Country:** China

**Facility:** Nanjing Drum Tower Hospital - The Affiliated Hospital of Nanjing University Medical School

**Status:** RECRUITING

**Location 30:**

**City:** Nanjing

**Country:** China

**Facility:** The Second Affiliated Hospital of Nanjing Medical University

**Status:** RECRUITING

**Location 31:**

**City:** Nantong

**Country:** China

**Facility:** Affiliated Hospital of Nantong University

**Status:** RECRUITING

**Location 32:**

**City:** Nanyang

**Country:** China

**Facility:** The First Affiliated Hospital of Nanyang Medical College

**Status:** RECRUITING

**Location 33:**

**City:** Panjin

**Country:** China

**Facility:** Panjin Liaohe Oilfield Gem Flower Hospital

**Status:** RECRUITING

**Location 34:**

**City:** Pingxiang

**Country:** China

**Facility:** Pingxiang People's Hospital

**Status:** RECRUITING

**Location 35:**

**City:** Qiqihar

**Country:** China

**Facility:** The First Hospital of Qiqihar

**Status:** RECRUITING

**Location 36:**

**City:** Sanmenxia

**Country:** China

**Facility:** Sanmenxia Central Hospital

**Status:** RECRUITING

**Location 37:**

**City:** Shanghai

**Country:** China

**Facility:** Huadong Hospital

**Status:** RECRUITING

**Location 38:**

**City:** Shanghai

**Country:** China

**Facility:** Shanghai Sixth People's Hospital

**Status:** RECRUITING

**Location 39:**

**City:** Shenyang

**Country:** China

**Facility:** Shengjing Hospital of China Medical University

**Status:** RECRUITING

**Location 40:**

**City:** Shenyang

**Country:** China

**Facility:** The People's Hospital of Liaoning Province

**Status:** RECRUITING

**Location 41:**

**City:** Wuhan

**Country:** China

**Facility:** Wuhan Third Hospital

**Status:** RECRUITING

**Location 42:**

**City:** Xi'an

**Country:** China

**Facility:** The First Affiliated Hospital of Xi'an Jiaotong Univerity

**Status:** RECRUITING

**Location 43:**

**City:** Xi'an

**Country:** China

**Facility:** The Second Affiliated Hospital of Xi'an Jiaotong University

**Status:** RECRUITING

**Location 44:**

**City:** Xiangtan

**Country:** China

**Facility:** The First People's Hospital of Xiangtan City

**Status:** RECRUITING

**Location 45:**

**City:** Xiangtan

**Country:** China

**Facility:** Xiangtan Central Hospital

**Status:** RECRUITING

**Location 46:**

**City:** Xianyang

**Country:** China

**Facility:** Xianyang Hospital of Yan'an University

**Status:** RECRUITING

**Location 47:**

**City:** Xuzhou

**Country:** China

**Facility:** Xuzhou Cancer Hospital

**Status:** RECRUITING

**Location 48:**

**City:** Yibin

**Country:** China

**Facility:** The Second People's Hospital of Yibin

**Status:** RECRUITING

**Location 49:**

**City:** Yiyang

**Country:** China

**Facility:** Yiyang Central Hospital

**Status:** RECRUITING

**Location 50:**

**City:** Yueyang

**Country:** China

**Facility:** Yueyang People's Hospital

**Status:** RECRUITING

**Location 51:**

**City:** Zaozhuang

**Country:** China

**Facility:** Shandong Healthcare Group Zaozhuang Central Hospital

**Status:** RECRUITING

**Location 52:**

**City:** Zhengzhou

**Country:** China

**Facility:** The Second Affiliated Hospital of Zhengzhou

**Status:** RECRUITING

**Location 53:**

**City:** Zhenjiang

**Country:** China

**Facility:** Affiliated Hospital of Jiangsu University

**Status:** RECRUITING

**Location 54:**

**City:** Zhumadian

**Country:** China

**Facility:** Zhumadian Central Hospital

**Status:** RECRUITING

#### Overall Officials

**Official 1:**

**Affiliation:** Shenzhen HighTide Biopharmaceutical Ltd.

**Name:** Kui Liu, MD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000044882

- Term: Glucose Metabolism Disorders

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000004700

- Term: Endocrine System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M7115

- Name: Diabetes Mellitus

- Relevance: HIGH

- As Found: Diabetes Mellitus

- ID: M7119

- Name: Diabetes Mellitus, Type 2

- Relevance: HIGH

- As Found: Type 2 Diabetes

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M25403

- Name: Glucose Metabolism Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003920

- Term: Diabetes Mellitus

- ID: D000003924

- Term: Diabetes Mellitus, Type 2

### Intervention Browse Module - Ancestors

- ID: D000077203

- Term: Sodium-Glucose Transporter 2 Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000007004

- Term: Hypoglycemic Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Gast

- Name: Gastrointestinal Agents

### Intervention Browse Module - Browse Leaves

- ID: M348449

- Name: Dapagliflozin

- Relevance: HIGH

- As Found: COPD

- ID: M11667

- Name: Metformin

- Relevance: LOW

- As Found: Unknown

- ID: M17329

- Name: Ursodeoxycholic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M1691

- Name: Sodium-Glucose Transporter 2 Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000529054

- Term: Dapagliflozin

### Misc Info Module

- Version Holder: 2024-05-31
