Clinical trial NCT06353347: Efficacy and Safety of Berberine Ursodeoxycholate (HTD1801) in Patients With Type 2 Diabetes Inadequately Controlled With Metformin
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: HighTide Biopharma Pty Ltd
Sponsor class: INDUSTRY
First posted: 2024-04-09
Enrollment: 551
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary Endpoint: mean change in HbA1c
timeFrame: 24 Weeks
Secondary outcomes:
measure: Double-blind (DB) Phase: mean change in fasting plasma glucose
timeFrame: 24 Weeks
measure: DB Phase: mean change in 2-hour postprandial glucose
timeFrame: 24 Weeks
measure: DB Phase: proportion of patients achieving HbA1c <7.0%
timeFrame: 24 Weeks
measure: DB Phase: proportion of patients achieving HbA1c <6.5%
timeFrame: 24 Weeks
measure: DB Phase: mean change in insulin sensitivity (HOMA-IR)
timeFrame: 24 Weeks
measure: DB Phase: mean change in low-density lipoprotein cholesterol (LDL-C)
timeFrame: 24 Weeks
Other outcomes:
measure: Open-Label Extension (OLE) Phase: mean change in HbA1c
timeFrame: 52 Weeks
measure: OLE Phase: mean change in 2-Hour postprandial glucose
timeFrame: 52 Weeks
measure: OLE Phase: proportion of patients achieving HbA1c <7.0%
timeFrame: 52 Weeks
measure: OLE Phase: proportion of patients achieving HbA1c <6.5%
timeFrame: 52 Weeks
measure: OLE Phase: mean change in insulin sensitivity (HOMA-IR)
timeFrame: 52 Weeks
measure: OLE Phase: mean change in LDL-C
timeFrame: 52 Weeks
Locations:
city: Baotou
country: China
facility: Baogang Hospital of Inner Mongolia
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Luhe Hospital Capital Medical University
city: Beijing
country: China
facility: Beijing Pinggu Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Peking University People's Hospital
city: Changchun
country: China
facility: The Second Norman Bethune Hospital of Jilin University
city: Changde
country: China
facility: The First People's Hospital of Changde City
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
city: Chongqing
country: China
facility: Chongqing University Three Gorges Hospital
city: Datong
country: China
facility: The Third People's Hospital of Datong
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
city: Handan
country: China
facility: Handan First Hospital
city: Harbin
country: China
facility: The Fourth Affiliated Hospital of Harbin Medical University
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
city: Hengshui
country: China
facility: Hengshui People's Hospital (Harrison International Peace Hospital)
city: Heze
country: China
facility: Heze Municipal Hospital
city: Huai'an
country: China
facility: Huai'an First People's Hospital
city: Huangshi
country: China
facility: Huangshi Central Hospital
city: Huizhou
country: China
facility: Huizhou Municipal Central Hospital
city: Huzhou
country: China
facility: Huzhou Central Hospital
city: Jinan
country: China
facility: Jinan Central Hospital
city: Jingzhou
country: China
facility: Jingzhou Central Hospital
city: Jinzhou
country: China
facility: Jinzhou Central Hospital
city: Kashgar
country: China
facility: The First People's Hospital of Kashgar
city: Langfang
country: China
facility: Hebei Petro China Center Hospital
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology (Jinghua)
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology (Kaiyuan)
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital - The Affiliated Hospital of Nanjing University Medical School
city: Nanjing
country: China
facility: Nanjing First Hospital
city: Nanjing
country: China
facility: Nanjing Jiangning Hospital
city: Nanjing
country: China
facility: Sir Run Run Hospital Nanjing Medical University
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University
city: Nanning
country: China
facility: The First People's Hospital of Nanning
city: Nanyang
country: China
facility: The First Affiliated Hospital of Nanyang Medical College
city: Panjin
country: China
facility: Panjin Liaohe Oilfield Gem Flower Hospital
city: Qiqihar
country: China
facility: The First Hospital of Qiqihar
city: Shanghai
country: China
facility: Shanghai East Hospital of Tongji University
city: Shanghai
country: China
facility: Shanghai Pudong New Area People's Hospital
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
city: Shenyang
country: China
facility: The Sixth People's Hospital of Shenyang
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
city: Shenzhen
country: China
facility: The University of Hong Kong - Shenzhen Hospital
city: Shiyan
country: China
facility: Taihe Hospital
city: Siping
country: China
facility: Siping City Central People's Hospital
city: Suzhou
country: China
facility: The First Affiliated Hospital of Suzhou University
city: Tianjin
country: China
facility: People's Hospital of Tianjin
city: Tonghua
country: China
facility: Tonghua Central Hospital
city: Wuhan
country: China
facility: The Central Hospital of Wuhan
city: Wuhu
country: China
facility: Yijishan Hospital of Wannan Medical College
city: Xiangtan
country: China
facility: The First People's Hospital of Xiangtan City
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
city: Yanan
country: China
facility: Yanan University Affiliated Hospital
city: Yueyang
country: China
facility: Yueyang People's Hospital
city: Yuncheng
country: China
facility: Yuncheng Central Hospital
city: Zhengzhou
country: China
facility: The Second Affiliated Hospital of Zhengzhou University
city: Zhenjiang
country: China
facility: Affiliated Hospital of Jiangsu University
city: Zhumadian
country: China
facility: Zhumadian Central Hospital
city: Zhuzhou
country: China
facility: Zhuzhou Central Hospital
city: Zibo
country: China
facility: Zibo Central Hospital
city: Zunyi
country: China
facility: The First People's Hospital of Zunyi
Study officials:
affiliation: Shenzhen HighTide Biopharmaceutical Ltd.
name: Kui Liu, MD
role: STUDY_DIRECTOR
References: