Clinical trial NCT03175120: A Trial Comparing Insulin Degludec/Liraglutide and Insulin Degludec in Combination With Metformin in Chinese Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Basal Insulin Therapy and Metformin With or Without One Other Oral Antidiabetic Drug (OAD)
Official title: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide and Insulin Degludec in Combination With Metformin in Chinese Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Basal Insulin Therapy and Metformin With or Without One Other OAD
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: 2017-06-05
Enrollment: 453
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 superiority of insulin degludec/liraglutide versus insulin degludec in controlling glycaemia in Chinese subjects with type 2 diabetes mellitus after 26 weeks of treatment


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 procedures to determine suitability for the trial - Male or female, age at least 18 years at the time of signing inform consent - Type 2 diabetes mellitus (clinically diagnosed) - HbA1c (glycosylated haemoglobin) above or equal to 7.5% by central laboratory analysis, with the aim of a median of 8.5%. When approximately 50% of the randomised subjects have an HbA1c above 8.5%, the remaining subjects randomised must have an HbA1c below or equal to 8.5% or when approximately 50% of the subjects randomised have an HbA1c below or equal to 8.5%, the remaining subjects randomised must have an HbA1c above 8.5% - Current treatment for at least 90 calendar days prior to screening with basal insulin plus metformin plus/minus α-glucosidase inhibitors, sulphonylureas, glinides or thiazolidinediones. Subjects should be on a stable dose for at least 60 calendar days prior to screening of: Basal insulin 20-50 units (U)/day (both inclusive) ( Individual fluctuations of plus/minus 5U during the 60 day period prior to the day of screening are acceptable.) on the day of screening in combination with: - 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 glinide (at least 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 (AGI) (at least half of the max approved dose according to local label) or - Metformin (above or equal to 1500 mg or max tolerated dose) and thiazolidinediones (at least half of the max approved dose according to local label) - Body mass index (BMI) above or equal to 24 kg/m\^2 Exclusion Criteria: Current use of any antidiabetic drug (except for basal insulin, metformin, α-glucosidase inhibitors, sulphonylureas, glinides or thiazolidinediones) or anticipated change in concomitant medication, that in the investigator´s opinion could interfere with glucose level (e.g. systemic corticosteroids) - Treatment with glucagon like peptide -1 receptor agonists, or dipeptidyl-peptidase-4 inhibitors or insulin (except for basal insulin) within 90 days prior to Visit 1 - 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 mm Hg or diastolic blood pressure above or equal to 100 mm Hg) - 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 Blood Glucose (BG) Confirmed Hypoglycaemic Episodes
timeFrame: Up to 26 weeks
measure: Change in Fasting Plasma Glucose (FPG)
timeFrame: Week 0, week 26
measure: Change in Waist Circumference
timeFrame: Week 0, week 26
measure: Change in Mean of the 9-point Self-measured Plasma Glucose (SMPG) Profile
timeFrame: Week 0, week 26
measure: Change in SMPG-mean Post Prandial Increments
timeFrame: Week 0, week 26
measure: Insulin Dose
timeFrame: Week 26
measure: SMPG-9-point Profile (Individual Points in the Profile)
timeFrame: 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 Total 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 Acids- Ratio to Baseline
timeFrame: Week 0, week 26
measure: Change in Fasting C-peptide- Ratio to Baseline
timeFrame: Week 0, week 26
measure: Change in Fasting 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: Participants Who Achieved HbA1c < 7.0%, ADA Target (Yes/no)
timeFrame: Week 26
measure: Participants Who Achieved HbA1c ≤ 6.5%, American Association of Clinical Endocrinologists (AACE) Target (Yes/no)
timeFrame: Week 26
measure: Participants Who Achieved HbA1c < 7.0% and Change From Baseline in Body Weight 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 Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes
timeFrame: Week 26
measure: Participants Who Achieved HbA1c ≤ 6.5% Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes
timeFrame: Week 26
measure: Participants Who Achieved HbA1c < 7.0% and Change From Baseline in Body Weight Below or Equal to Zero and Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes
timeFrame: Week 26
measure: Participants Who Achieved HbA1c ≤ 6.5% and Change From Baseline in Body Weight Below or Equal to Zero and Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes
timeFrame: Week 26
measure: Number of Treatment-emergent Adverse Events (TEAEs)
timeFrame: Weeks 0-27
measure: Number of Treatment-emergent Nocturnal Severe or BG Confirmed Hypoglycaemic Episodes
timeFrame: Weeks 0-27
measure: Number of Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Weeks 0-27
measure: Number of Treatment-emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Weeks 0-27
measure: Number of Treatment-emergent Hypoglycaemic Episodes According to ADA Definition
timeFrame: Weeks 0-27
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 Biochemical Parameter- Amylase, Lipase, Creatinine Kinase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP)
timeFrame: Week 0, week 26
measure: Change in Biochemical Parameter-calcium (Total), Albumin Corrected Calcium, Potassium, Sodium, Urea
timeFrame: Week 0, week 26
measure: Change in Albumin
timeFrame: Week 0, week 26
measure: Change in Total Bilirubin
timeFrame: Week 0, week 26
measure: Change in Creatinine
timeFrame: Week 0, week 26
measure: Change in Total Protein
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter- Haematocrit
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter- Haemoglobin
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter- Leukocytes and Thrombocytes
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter- Erythrocytes
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter- Basophils
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter- Eosinophils
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter- Lymphocytes
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter- Monocytes
timeFrame: Week 0, week 26
measure: Change in Haematological Parameter- Neutrophils
timeFrame: Week 0, week 26
measure: Change in Calcitonin
timeFrame: Week 0, week 26
measure: Urinalysis (Erythrocytes, Protein, Glucose and Ketones)
timeFrame: Week 0, week 26
measure: Anti-insulin Degludec Specific Antibodies
timeFrame: Week 27
measure: Antibodies Cross-reacting to Human Insulin
timeFrame: Week 27
measure: Total Insulin Antibodies
timeFrame: Week 27
measure: Occurrence of Anti-liraglutide Antibodies (Yes/no)
timeFrame: Week 27
measure: Occurrence of Anti-liraglutide Antibodies Cross Reacting Native Glucagon-like Peptide-1 (GLP-1)
timeFrame: Week 27
measure: Occurrence of Neutralising Liraglutide Antibodies
timeFrame: Week 27
measure: Occurrence of Neutralising Liraglutide Antibodies Cross Reacting Native GLP-1
timeFrame: Week 27
Other outcomes:
Locations:
city: Hefei
country: China
facility: Novo Nordisk Investigational Site
state: Anhui
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: 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: Guangzhou
country: China
facility: Novo Nordisk Investigational Site
state: Guangdong
city: Guangzhou
country: China
facility: Novo Nordisk Investigational Site
state: Guangdong
city: Hengshui
country: China
facility: Novo Nordisk Investigational Site
state: Hebei
city: Shijiazhuang
country: China
facility: Novo Nordisk Investigational Site
state: Hebei
city: Tangshan
country: China
facility: Novo Nordisk Investigational Site
state: Hebei
city: Harbin
country: China
facility: Novo Nordisk Investigational Site
state: Heilongjiang
city: Yueyang
country: China
facility: Novo Nordisk Investigational Site
state: Hunan
city: Huhehaote
country: China
facility: Novo Nordisk Investigational Site
state: Inner Mongolia
city: Huhhot
country: China
facility: Novo Nordisk Investigational Site
state: Inner Mongolia
city: Changzhou
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: Changchun
country: China
facility: Novo Nordisk Investigational Site
state: Jilin
city: Siping
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: 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: Taiyuan
country: China
facility: Novo Nordisk Investigational Site
state: Shanxi
city: Tianjin
country: China
facility: Novo Nordisk Investigational Site
state: Tianjin
city: Kunming
country: China
facility: Novo Nordisk Investigational Site
state: Yunnan
city: Shatin, New Territories
country: Hong Kong
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR,1452)
role: STUDY_DIRECTOR
References: