Clinical trial NCT04373967: Study to Assess the Efficacy and Safety of Liraglutide in the Treatment of Type 2 Diabetes
Official title: A Phase III,Randomized,Parallel,Open-label,Multicenter Trial to Compare the Efficacy and Safety of Liraglutide and Victoza® in Patients With Type 2 Diabetes Inadequately Controlled by Oral Metformin Alone
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-05-05
Enrollment: 424
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: Liraglutide injection is a glucagon-like peptide-1 (GLP-1) analogue that activates the cyclic adenosine monophosphate (cAMP) and mitogen-activated protein kinase (MAPK) pathway by binding to the GLP-1 receptor (GLP-1R),thus,it has physiological effects such as glucose-dependent insulin synthesis and secretion, inhibition of β-cell apoptosis, promotion of β-cell proliferation and regeneration, inhibition of glucagon secretion, reduction of food intake, delay of gastric emptying, enhancement of glucose utilization in peripheral tissues and reduction of glycogen output. Liraglutide injection,developed and marketed as Victoza® by Novo Nordisk,is indicated for the treatment of patients with type 2 diabetes and was approved by the U.S. Food and Drug Administration in 2010.This 26-week trial compares the effectivity on glycaemic control,safety and immunogenicity of liraglutide injection and Victoza® in patients with type 2 diabetes inadequately controlled by oral metformin alone.


Eligibility criteria: Inclusion Criteria:

* Diagnosed as type 2 diabetes.
* Stably daily dose of metformin alone\[between the dose of 1500mg and 2000mg inclusive\] for at least 12 weeks prior to day of screening .
* HbA1c(glycosylated haemoglobin) of 7-11%(both inclusive).
* Body mass index (BMI) of 18.5-45 kg/m2(both inclusive).
* The patient must give informed consent to the study before the trial and voluntarily sign the informed consent form.
* The patient can communicate well with the researcher and complete the study in accordance with the research regulations.

Exclusion Criteria:

* Diagnosed as type 1 or other types of diabetes.
* Treatment with glucagon-like peptide-1 (GLP-1) receptor agonist, dipeptidyl peptidase-4 (DPP-4) inhibitor and insulin treatment within 3 months before screening.\[short term (cumulative use ≤7 days) insulin therapy due to intermittent disease is excluded\]
* Treatment with systemic glucocorticoid therapy within 3 months before screening\[topical medication or inhaled product is excluded\] .
* Treatment with Chinese medicine preparations having hypoglycemic effects within 1 month before screening.
* Patients with recurrent severe or unconscious hypoglycemia within 3 months before screening.
* Patients with acute metabolic complications (ketoacidosis, lactic acidosis or hypertonic coma, etc.) within 6 months before screening.
* History of chronic pancreatitis or idiopathic acute pancreatitis, or suffering from acute or chronic pancreatitis during screening, or blood amylase ≥ 3 times of the upper limit of normal value, or triglycerides ≥ 8.0 mmol / L.
* Fasting blood-glucose(FBG)≥15.0 mmol / L on the day of screening.
* Personal or family history of medullary thyroid carcinoma (MTC) or type 2 multiple endocrine adenoma (MEN2).
* Patients with obvious liver and kidney dysfunction (alanine aminotransferase (ALT)\> 2.5 × upper normal value (ULN), aspartate aminotransferase (AST)\> 2.5 ULN, glomerular filtration rate \<60 Milliliter(mL) / min / 1.73m2
* Hemoglobin \<lower limit of normal value.
* Hyperthyroidism is being treated or the dosage of hypothyroidism is not stable within 6 months.
* Uncontrolled or poorly treated hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg).
* Patients with decompensated heart failure (NYHA grades III and IV), unstable angina, stroke or transient ischemic attack, myocardial infarction, severe arrhythmia, cardiac surgery or vascular reconstruction performed (including coronary artery bypass grafting or percutaneous coronary intervention) within 6 months before screening.
* Proliferative retinopathy or macular disease (macular edema) that requires urgent treatment.
* Malignant tumors (except basal cell carcinoma or phosphorous cell skin cancer) diagnosed within the past 5 years.
* Patients with severe chronic gastrointestinal disease (such as active peptic ulcer) and severe infections.
* People who are allergic to any of the ingredients in metformin, liraglutide injection and Victoza®.
* Participated in any other clinical trials within 3 months before screening.
* Pregnant women, lactating women and women of reproductive age who did not take appropriate contraception (sterilization, intrauterine devices, oral contraceptives or barrier contraception) during the trial.
* History of psychotropic substance abuse, alcohol abuse or drug addiction.
* Patients judged as unsuitable participants of the trial by researchers or with poor compliance.
* According to the investigators' judgment, there are seriously concomitant diseases endanger the safety of the patient or prevent the patient from completing the study.

Primary outcomes:
measure: glycated hemoglobin (HbA1c)
timeFrame: week 0,week 26
Secondary outcomes:
measure: Body weight
timeFrame: week 0,week 26
measure: Proportion of achieving HbA1c target (<7.0% or ≤6.5%)
timeFrame: week 0,week 26
measure: HbA1c change from baseline
timeFrame: week 0,week 14
measure: Changes in fasting venous blood glucose (FPG).
timeFrame: week 0,week 14,week 26
measure: Changes in 2h-Postprandial Blood Glucose(2h-PBG).
timeFrame: week 0,week 14,week 26
measure: Changes in fasting insulin.
timeFrame: week 0,week 14,week 26
measure: Changes in fasting C peptide.
timeFrame: week 0,week 14,week 26
measure: Changes in systolic blood pressure.
timeFrame: week 0,week 14,week 26
measure: Changes in diastolic blood pressure.
timeFrame: week 0,week 14,week 26
measure: Number of adverse events and serious adverse events during exposure to trail product.
timeFrame: week 0-26
measure: Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes during exposure to trail product.
timeFrame: week 0-26
measure: Positive rate of liraglutide anti-drug antibody(ADA).
timeFrame: week 0-26
measure: Percentage of participants with clinically significant change from baseline in vital signs.
timeFrame: week 0-26
measure: Percentage of participants with clinically significant change from baseline in laboratory parameters.
timeFrame: week 0-26
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The Second People's Hospital of Heifei
state: Anhui
city: Ma'anshan
country: China
facility: Ma'anshan People's Hospital
state: Anhui
city: Wuhu
country: China
facility: Yijishan Hospital of Wannan Medical College
state: Anhui
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: The Ninth People's Hospital of Chongqing
state: Chongqing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Zhanjiang
country: China
facility: Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou People's Hospital
state: Guangxi
city: Nanning
country: China
facility: The First People's Hospital of Nanning
state: Guangxi
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: The Fourth Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Harbin
country: China
facility: The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Xinxiang
country: China
facility: Xinxiang Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: People's Hospital of Zhengzhou
state: Henan
city: Wuhan
country: China
facility: The Third People's Hospital of Hebei
state: Hubei
city: Lianyungang
country: China
facility: The Second People's Hospital of Lianyungang
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Jiangning Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Third People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Nanchang First Hospital
state: Jiangxi
city: Changchun
country: China
facility: Affiliated Hospital of Changchun University of Chinese Medicine
state: Jilin
city: Changchun
country: China
facility: Jilin Province FAW General Hospital
state: Jilin
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Tonghua
country: China
facility: Meihekou Central Hospital
state: Jilin
city: Dalian
country: China
facility: Dalian Municipal Central Hospital Affiliated of Dalian Medical University
state: Liangning
city: Yinchuan
country: China
facility: People's Hospital of Ningxia Hui Autonomous Region
state: Ningxia
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Weifang
country: China
facility: Weifang Traditional Chinese Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Pudong Hospital
state: Shanghai
city: Changzhi
country: China
facility: Changzhi People's Hospital
state: Shanxi
city: Changzhi
country: China
facility: Peace Hospital Affiliated to Changzhi Medical College
state: Shanxi
city: Jincheng
country: China
facility: Jincheng General Hospital
state: Shanxi
city: Taiyuan
country: China
facility: Second Hospital of Shanxi Medical University
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong Univesity
state: Shanxi
city: Xian
country: China
facility: The First Affiliated Hospital of The Fourth Military Medical University
state: Shanxi
city: Xian
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital)
state: Shanxi
city: Yuncheng
country: China
facility: Yuncheng Central Hospital
state: Shanxi
city: Tianjin
country: China
facility: General Hospital of Tianjin Medical University
state: Tianjin
city: Tianjin
country: China
facility: Tianjin First Central Hospital
state: Tianjin
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou First People's Hospital
state: Zhejiang
Study officials:
References: