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

Novo Nordisk A/S1 site in 1 country453 target enrollmentMay 26, 2017

ConditionsDiabetes Diabetes Mellitus, Type 2

InterventionsInsulin degludec/liraglutide Insulin degludec

DrugsInsulin degludec/liraglutide Insulin degludec

Overview

Phase: Phase 3
Intervention: Insulin degludec/liraglutide
Conditions: Diabetes
Sponsor: Novo Nordisk A/S
Enrollment: 453
Locations: 1
Primary Endpoint: Change in HbA1c
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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

Registry

clinicaltrials.gov

Start Date

May 26, 2017

End Date

April 4, 2019

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novo Nordisk A/S

Responsible Party

Sponsor

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)

Arms & Interventions

Insulin degludec/liraglutide

Intervention: Insulin degludec/liraglutide

Insulin degludec

Intervention: Insulin degludec

Outcomes

Primary Outcomes

Change in HbA1c

Time Frame: Week 0, week 26

Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 26 is presented.

Secondary Outcomes

Change in Fasting Plasma Glucose (FPG)(Week 0, week 26)
Change in Body Weight(Week 0, week 26)
Number of Treatment-emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes(Up to 26 weeks)
Change in Mean of the 9-point Self-measured Plasma Glucose (SMPG) Profile(Week 0, week 26)
Insulin Dose(Week 26)
SMPG-9-point Profile (Individual Points in the Profile)(Week 26)
Change in Fasting High-density Lipoprotein (HDL) Cholesterol- Ratio to Baseline(Week 0, week 26)
Change in Fasting Very Low-density Lipoprotein (VLDL) Cholesterol- Ratio to Baseline(Week 0, week 26)
Change in HOMA-B (Beta-cell Function)- Ratio to Baseline(Week 0, week 26)
Participants Who Achieved HbA1c < 7.0% and Change From Baseline in Body Weight Below or Equal to Zero(Week 26)
Participants Who Achieved HbA1c ≤ 6.5% and Change From Baseline in Body Weight Below or Equal to Zero(Week 26)
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(Week 26)
Change in Haematological Parameter- Haematocrit(Week 0, week 26)
Change in Haematological Parameter- Haemoglobin(Week 0, week 26)
Change in Waist Circumference(Week 0, week 26)
Change in SMPG-mean Post Prandial Increments(Week 0, week 26)
Change in Fasting Low-density Lipoprotein (LDL) Cholesterol- Ratio to Baseline(Week 0, week 26)
Change in Fasting Total Cholesterol- Ratio to Baseline(Week 0, week 26)
Change in Fasting Triglycerides- Ratio to Baseline(Week 0, week 26)
Change in Fasting Free Fatty Acids- Ratio to Baseline(Week 0, week 26)
Change in Fasting Insulin- Ratio to Baseline(Week 0, week 26)
Change in Fasting C-peptide- Ratio to Baseline(Week 0, week 26)
Participants Who Achieved HbA1c < 7.0%, ADA Target (Yes/no)(Week 26)
Participants Who Achieved HbA1c ≤ 6.5%, American Association of Clinical Endocrinologists (AACE) Target (Yes/no)(Week 26)
Number of Treatment-emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes(Weeks 0-27)
Change in Blood Pressure (Systolic and Diastolic Blood Pressure)(Week 0, week 26)
Change in Biochemical Parameter-calcium (Total), Albumin Corrected Calcium, Potassium, Sodium, Urea(Week 0, week 26)
Change in Albumin(Week 0, week 26)
Change in Total Bilirubin(Week 0, week 26)
Change in Creatinine(Week 0, week 26)
Change in Fasting Glucagon- Ratio to Baseline(Week 0, week 26)
Participants Who Achieved HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes(Week 26)
Participants Who Achieved HbA1c ≤ 6.5% Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes(Week 26)
Number of Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes(Weeks 0-27)
Change in Biochemical Parameter- Amylase, Lipase, Creatinine Kinase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP)(Week 0, week 26)
Eye Examination(Week -2, week 26)
Change in Total Protein(Week 0, week 26)
Change in Haematological Parameter- Leukocytes and Thrombocytes(Week 0, week 26)
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(Week 26)
Number of Treatment-emergent Adverse Events (TEAEs)(Weeks 0-27)
Number of Treatment-emergent Nocturnal Severe or BG Confirmed Hypoglycaemic Episodes(Weeks 0-27)
Number of Treatment-emergent Hypoglycaemic Episodes According to ADA Definition(Weeks 0-27)
Change in Physical Examination(Week -2, week 26)
Change in Electrocardiogram (ECG)(Week -2, week 26)
Change in Pulse(Week 0, week 26)
Change in Haematological Parameter- Erythrocytes(Week 0, week 26)
Change in Haematological Parameter- Basophils(Week 0, week 26)
Change in Haematological Parameter- Eosinophils(Week 0, week 26)
Change in Haematological Parameter- Lymphocytes(Week 0, week 26)
Change in Haematological Parameter- Neutrophils(Week 0, week 26)
Urinalysis (Erythrocytes, Protein, Glucose and Ketones)(Week 0, week 26)
Anti-insulin Degludec Specific Antibodies(Week 27)
Antibodies Cross-reacting to Human Insulin(Week 27)
Change in Calcitonin(Week 0, week 26)
Total Insulin Antibodies(Week 27)
Occurrence of Anti-liraglutide Antibodies (Yes/no)(Week 27)
Occurrence of Neutralising Liraglutide Antibodies(Week 27)
Change in Haematological Parameter- Monocytes(Week 0, week 26)
Occurrence of Anti-liraglutide Antibodies Cross Reacting Native Glucagon-like Peptide-1 (GLP-1)(Week 27)
Occurrence of Neutralising Liraglutide Antibodies Cross Reacting Native GLP-1(Week 27)