Clinical trial NCT03172494: A Trial Comparing Insulin Degludec/Liraglutide, Insulin Degludec, and Liraglutide in Chinese Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetic Drugs (OADs)
Official title: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec, and Liraglutide in Chinese Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetic Drugs (OADs)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2017-06-01
Enrollment: 720
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Asia. The aim of this trial is to confirm the efficacy of insulin degludec/liraglutide in controlling glycaemia in Chinese subjects with type 2 diabetes mellitus inadequately controlled on oral antidiabetic agents


Eligibility criteria: Inclusion Criteria:

* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
* Type 2 diabetes mellitus (clinically diagnosed)
* Male or female, age at least 18 years at the time of signing informed consent
* HbA1c 7.0-10.0 % (both inclusive) by central laboratory analysis, with the aim of a median of8.3%. When approximately 50% of the randomised subjects have an HbA1c above 8.3%, the remaining subjects randomised must have an HbA1c below or equal to 8.3%; or when approximately 50% of the randomised subjects have an HbA1c below or equal to 8.3%, the remaining subjects randomised must have an HbA1c above 8.3%
* Current treatment for at least 90 calendar days prior to screening with metformin plus/minus one other OAD: α-glucosidase inhibitors, sulphonylureas, glinides or thiazolidinediones. For above or equal to 60 calendar days prior to screening subjects should be on a stable dose of:
* Metformin (above or equal to 1500 mg or max tolerated dose) or
* Metformin (above or equal to 1500 mg or max tolerated dose) and sulphonylureas (above or equal to half of the max approved dose according to local label) or
* Metformin (above or equal to 1500 mg or max tolerated dose) and glinides (above or equal to half of the max approved dose according to local label) or
* Metformin (above or equal to 1500 mg or max tolerated dose) and α-glucosidase inhibitors (above or equal to half of the max approved dose according to local label) or
* Metformin (above or equal to 1500 mg or max tolerated dose) and thiazolidinediones (above or equal to half of the max approved dose according to local label)

Exclusion Criteria:

* Treatment with insulin (except for short-term treatment at the discretion of the investigator)
* Treatment with glucagon-like-peptide-1 receptor agonists or dipeptidyl-peptidase-4 inhibitors within 90 days prior to screening
* Impaired liver function, defined as alanine aminotransferase above or equal to 2.5 times upper normal range
* Impaired renal function defined as serum-creatinine above or equal to 133 μmol/L for males and above or equal to 125 μmol/L for females, or as defined according to local contraindications for metformin
* Screening calcitonin above or equal to 50 ng/L
* Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2)
* Cardiac disorder defined as: congestive heart failure (NYHA class III-IV), diagnosis of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the last 12 months prior to screening and/or planned coronary, carotid or peripheral artery revascularisation procedures
* Severe uncontrolled treated or untreated hypertension (systolic blood pressure above or equal to 180 mmHg or diastolic blood pressure above or equal to 100 mmHg
* Proliferative retinopathy or maculopathy (macular oedema), requiring acute treatment
* History of pancreatitis (acute or chronic)

Primary outcomes:
measure: Change in HbA1c
timeFrame: Week 0, week 26
Secondary outcomes:
measure: Change in Body Weight
timeFrame: Week 0, week 26
measure: Number of Treatment Emergent Severe or BG Confirmed Hypoglycaemic Episodes
timeFrame: Weeks 0-26
measure: Insulin Dose
timeFrame: Week 26
measure: Participants Who Achieved HbA1c < 7.0%, American Diabetes Association (ADA) Target (Yes/no)
timeFrame: Week 26
measure: Participants Who Achieved HbA1c ≤ 6.5%, International Diabetes Federation (IDF) Target (Yes/no)
timeFrame: Week 26
measure: Participants Who Achieved HbA1c <7.0% and Change in Body Weight From Baseline Below or Equal to Zero
timeFrame: Week 26
measure: Participants Who Achieved HbA1c ≤ 6.5% and Change From Baseline in Body Weight Below or Equal to Zero
timeFrame: Week 26
measure: Participants Who Achieved HbA1c < 7.0% Without Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes
timeFrame: Week 26
measure: Participants Who Achieved HbA1c ≤ 6.5% Without Severe or BG Confirmed Hypoglycaemic Episodes
timeFrame: Week 26
measure: Participants Who Achieved HbA1c < 7.0% Without Severe or BG Confirmed Episodes, and Change From Baseline in Body Weight Below or Equal to Zero.
timeFrame: Week 26
measure: Participants Who Achieved HbA1c ≤ 6.5% Without Severe or BG Confirmed Episodes and Change From Baseline in Body Weight Below or Equal to Zero.
timeFrame: Week 26
measure: Change in Fasting Plasma Glucose (FPG)
timeFrame: Week 0, week 26
measure: Change in Waist Circumferance
timeFrame: Week 0, week 26
measure: 9-point SMPG Profile
timeFrame: Week 26
measure: Change in Mean of 9-point SMPG Profile
timeFrame: Week 0, week 26
measure: Change in Mean Post-prandial Plasma Glucose (PG) Increments
timeFrame: Week 0, week 26
measure: Change in Fasting C-peptide - Ratio to Baseline
timeFrame: Week 0, week 26
measure: Change in Fasting Human Insulin - Ratio to Baseline
timeFrame: Week 0, week 26
measure: Change in Fasting Glucagon - Ratio to Baseline
timeFrame: Week 0, week 26
measure: Change in HOMA-B (Beta Cell Function)- Ratio to Baseline
timeFrame: Week 0, week 26
measure: Change in Fasting Total Cholesterol - Ratio to Baseline
timeFrame: Week 0, week 26
measure: Change in Fasting High Density Lipoprotein (HDL) Cholesterol- Ratio to Baseline
timeFrame: Week 0, week 26
measure: Change in Fasting Low Density Lipoprotein (LDL) Cholesterol- Ratio to Baseline
timeFrame: Week 0, week 26
measure: Change in Fasting Very Low-density Lipoprotein (VLDL) Cholesterol- Ratio to Baseline
timeFrame: Week 0, week 26
measure: Change in Fasting Triglycerides - Ratio to Baseline.
timeFrame: Week 0, week 26
measure: Change in Fasting Free Fatty Acid - Ratio to Baseline
timeFrame: Week 0, week 26
measure: Number of Treatment-emergent Adverse Events (TEAE)
timeFrame: Weeks 0-26
measure: Number of Treatment Emergent Nocturnal Severe or BG Confirmed Hypoglycaemic Episodes.
timeFrame: Weeks 0-26
measure: Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes.
timeFrame: Weeks 0-26
measure: Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Weeks 0-26
measure: Number of Treatment Emergent Hypoglycaemic Episodes According to ADA Definition
timeFrame: Weeks 0-26
measure: Change in Physical Examination
timeFrame: Week -2, week 26
measure: Eye Examination
timeFrame: Week -2, Week 26
measure: Change in Electrocardiogram (ECG)
timeFrame: Week -2, week 26
measure: Change in Pulse
timeFrame: Week 0, week 26
measure: Change in Blood Pressure (Systolic and Diastolic Blood Pressure)
timeFrame: Week 0, week 26
measure: Change in Biochemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase, Amalyse, Lipase, Creatiine Kinase Serum
timeFrame: Week 0, week 26
measure: Change in Biochemistry Parameters (Albumin Serum, Total Protein)
timeFrame: Week 0, week 26
measure: Change in Biochemistry Parameters: Calcium Serum (Total), Calcium Corrected Serum, Potassium Serum, Sodium Serum, Urea Serum
timeFrame: Week 0, week 26
measure: Change in Biochemistry Parameters: Total Bilirubin Serum, Creatinine Serum
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter: Erythrocytes Blood
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter: Haematocrits
timeFrame: Week 0, week 26
measure: Change in Haemotological Parameter- Eosinophils
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter - Neutrophils
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter: Basophils
timeFrame: Week 0, week 26
measure: Change in Haemotological Parameter- Monocytes
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter - Lymphocytes
timeFrame: Week 0, week 26
measure: Change in Haematology: Haemoglobin Blood
timeFrame: Week 0, week 26
measure: Change in Haematologcal Parameter: Leukocytes
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter: Thrombocytes
timeFrame: Week 0, week 26
measure: Change in Calcitonin
timeFrame: Week 0, week 26
measure: Urinalysis (Protein, Glucose, Erythrocytes and Ketones)
timeFrame: Week 0, week 26
measure: Occurence of Anti-insulin Degludec Specific Antibodies
timeFrame: Week 27
measure: Occurence of Antibodies Cross-reacting to Human Insulin
timeFrame: Week 27
measure: Occurence of Total Insulin Antibodies
timeFrame: Week 27
measure: Occurence of Anti-liraglutide Antibodies
timeFrame: Week 27
measure: Occurence of Antibodies Cross-reacting to Native Glucagon-like Peptide (GLP-1)
timeFrame: Week 27
measure: Occurence of Neutralising Liraglutide Antibodies
timeFrame: Week 27
measure: Occurence of Neutralising Antibodies Cross-reacting to Native GLP-1
timeFrame: Week 27
measure: Serum Concentrations of Insulin Degludec
timeFrame: Week 0, week 26
measure: Plasma Concentration of Liraglutide
timeFrame: Week 0, week 26
Other outcomes:
Locations:
city: Hefei
country: China
facility: Novo Nordisk Investigational Site
state: Anhui
city: Beijing
country: China
facility: Novo Nordisk Investigational Site
state: Beijing
city: Beijing
country: China
facility: Novo Nordisk Investigational Site
state: Beijing
city: ChongQing
country: China
facility: Novo Nordisk Investigational Site
state: Chongqing
city: Fuzhou
country: China
facility: Novo Nordisk Investigational Site
state: Fujian
city: Fuzhou
country: China
facility: Novo Nordisk Investigational Site
state: Fujian
city: Guangzhou
country: China
facility: Novo Nordisk Investigational Site
state: Guangdong
city: Guangzhou
country: China
facility: Novo Nordisk Investigational Site
state: Guangdong
city: Guangzhou
country: China
facility: Novo Nordisk Investigational Site
state: Guangdong
city: Cangzhou
country: China
facility: Novo Nordisk Investigational Site
state: Hebei
city: Shijiazhuang
country: China
facility: Novo Nordisk Investigational Site
state: Hebei
city: Shijiazhuang
country: China
facility: Novo Nordisk Investigational Site
state: Hebei
city: Changzhou
country: China
facility: Novo Nordisk Investigational Site
state: Jiangsu
city: Huai'an
country: China
facility: Novo Nordisk Investigational Site
state: Jiangsu
city: Huai'an
country: China
facility: Novo Nordisk Investigational Site
state: Jiangsu
city: Nanjing
country: China
facility: Novo Nordisk Investigational Site
state: Jiangsu
city: Nanjing
country: China
facility: Novo Nordisk Investigational Site
state: Jiangsu
city: Nanjing
country: China
facility: Novo Nordisk Investigational Site
state: Jiangsu
city: Zhenjiang
country: China
facility: Novo Nordisk Investigational Site
state: Jiangsu
city: Nanchang
country: China
facility: Novo Nordisk Investigational Site
state: Jiangxi
city: Changchun
country: China
facility: Novo Nordisk Investigational Site
state: Jilin
city: Dalian
country: China
facility: Novo Nordisk Investigational Site
state: Liaoning
city: Yinchuan
country: China
facility: Novo Nordisk Investigational Site
state: Ningxia
city: Xi'an
country: China
facility: Novo Nordisk Investigational Site
state: Shaanxi
city: Jinan
country: China
facility: Novo Nordisk Investigational Site
state: Shandong
city: Pudong New District
country: China
facility: Novo Nordisk Investigational Site
state: Shanghai
city: Shanghai
country: China
facility: Novo Nordisk Investigational Site
state: Shanghai
city: Shanghai
country: China
facility: Novo Nordisk Investigational Site
state: Shanghai
city: Shanghai
country: China
facility: Novo Nordisk Investigational Site
state: Shanghai
city: Shanghai
country: China
facility: Novo Nordisk Investigational Site
state: Shanghai
city: Shanghai
country: China
facility: Novo Nordisk Investigational Site
state: Shanghai
city: Shanghai
country: China
facility: Novo Nordisk Investigational Site
state: Shanghai
city: Shanghai
country: China
facility: Novo Nordisk Investigational Site
state: Shanghai
city: Tianjin
country: China
facility: Novo Nordisk Investigational Site
state: Tianjin
city: Kunming
country: China
facility: Novo Nordisk Investigational Site
state: Yunnan
city: Fuzhou
country: China
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR,1452)
role: STUDY_DIRECTOR
References:
citation: Wang W, Agner BFR, Luo B, Liu L, Liu M, Peng Y, Qu S, Stachlewska KA, Wang G, Yuan G, Zhang Q, Ning G. DUAL I China: Improved glycemic control with IDegLira versus its individual components in a randomized trial with Chinese participants with type 2 diabetes uncontrolled on oral antidiabetic drugs. J Diabetes. 2022 Jun;14(6):401-413. doi: 10.1111/1753-0407.13286.