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)

Novo Nordisk A/S1 site in 1 country720 target enrollmentMay 26, 2017

ConditionsDiabetes Diabetes Mellitus, Type 2

InterventionsLiraglutide Insulin degludec/liraglutide Insulin degludec

DrugsInsulin degludec/liraglutide Insulin degludec Liraglutide

Overview

Phase: Phase 3
Intervention: Liraglutide
Conditions: Diabetes
Sponsor: Novo Nordisk A/S
Enrollment: 720
Locations: 1
Primary Endpoint: Change in HbA1c
Status: Completed
Last Updated: 3 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 efficacy of insulin degludec/liraglutide in controlling glycaemia in Chinese subjects with type 2 diabetes mellitus inadequately controlled on oral antidiabetic agents

Registry

clinicaltrials.gov

Start Date

May 26, 2017

End Date

July 13, 2019

Last Updated

3 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 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)

Arms & Interventions

Liraglutide

Intervention: Liraglutide

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 HbA1c from baseline (week 0) after 26 weeks of treatment is presented.

Secondary Outcomes

Participants Who Achieved HbA1c < 7.0% Without Severe or BG Confirmed Episodes, and Change From Baseline in Body Weight Below or Equal to Zero.(Week 26)
Change in Waist Circumferance(Week 0, week 26)
Change in Mean of 9-point SMPG Profile(Week 0, week 26)
Change in Fasting High Density Lipoprotein (HDL) Cholesterol- Ratio to Baseline(Week 0, week 26)
Change in Mean Post-prandial Plasma Glucose (PG) Increments(Week 0, week 26)
Change in Fasting Total 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 Fasting Human Insulin - Ratio to Baseline(Week 0, week 26)
Change in HOMA-B (Beta Cell Function)- Ratio to Baseline(Week 0, week 26)
Change in Fasting Glucagon - Ratio to Baseline(Week 0, week 26)
Change in Fasting Triglycerides - Ratio to Baseline.(Week 0, week 26)
Change in Fasting Free Fatty Acid - Ratio to Baseline(Week 0, week 26)
Change in Fasting Low Density Lipoprotein (LDL) Cholesterol- Ratio to Baseline(Week 0, week 26)
Number of Treatment-emergent Adverse Events (TEAE)(Weeks 0-26)
Number of Treatment Emergent Nocturnal Severe or BG Confirmed Hypoglycaemic Episodes.(Weeks 0-26)
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes.(Weeks 0-26)
Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes(Weeks 0-26)
Number of Treatment Emergent Hypoglycaemic Episodes According to ADA Definition(Weeks 0-26)
Change in Physical Examination(Week -2, week 26)
Eye Examination(Week -2, Week 26)
Change in Electrocardiogram (ECG)(Week -2, week 26)
Change in Pulse(Week 0, week 26)
Change in Blood Pressure (Systolic and Diastolic Blood Pressure)(Week 0, week 26)
Change in Biochemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase, Amalyse, Lipase, Creatiine Kinase Serum(Week 0, week 26)
Change in Biochemistry Parameters: Calcium Serum (Total), Calcium Corrected Serum, Potassium Serum, Sodium Serum, Urea Serum(Week 0, week 26)
Change in Biochemistry Parameters: Total Bilirubin Serum, Creatinine Serum(Week 0, week 26)
Change in Biochemistry Parameters (Albumin Serum, Total Protein)(Week 0, week 26)
Change in Haematological Parameter: Erythrocytes Blood(Week 0, week 26)
Change in Haematological Parameter: Haematocrits(Week 0, week 26)
Change in Haemotological Parameter- Eosinophils(Week 0, week 26)
Change in Haematological Parameter - Neutrophils(Week 0, week 26)
Change in Haematological Parameter: Basophils(Week 0, week 26)
Change in Haemotological Parameter- Monocytes(Week 0, week 26)
Change in Haematological Parameter - Lymphocytes(Week 0, week 26)
Change in Haematology: Haemoglobin Blood(Week 0, week 26)
Change in Haematologcal Parameter: Leukocytes(Week 0, week 26)
Change in Haematological Parameter: Thrombocytes(Week 0, week 26)
Change in Calcitonin(Week 0, week 26)
Urinalysis (Protein, Glucose, Erythrocytes and Ketones)(Week 0, week 26)
Occurence of Anti-insulin Degludec Specific Antibodies(Week 27)
Occurence of Antibodies Cross-reacting to Human Insulin(Week 27)
Occurence of Total Insulin Antibodies(Week 27)
Occurence of Anti-liraglutide Antibodies(Week 27)
Occurence of Antibodies Cross-reacting to Native Glucagon-like Peptide (GLP-1)(Week 27)
Occurence of Neutralising Liraglutide Antibodies(Week 27)
Occurence of Neutralising Antibodies Cross-reacting to Native GLP-1(Week 27)
Serum Concentrations of Insulin Degludec(Week 0, week 26)
Plasma Concentration of Liraglutide(Week 0, week 26)
Participants Who Achieved HbA1c < 7.0%, American Diabetes Association (ADA) Target (Yes/no)(Week 26)
Participants Who Achieved HbA1c < 7.0% Without Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes(Week 26)
Participants Who Achieved HbA1c ≤ 6.5% Without Severe or BG Confirmed Episodes and Change From Baseline in Body Weight Below or Equal to Zero.(Week 26)
Change in Fasting Plasma Glucose (FPG)(Week 0, week 26)
Participants Who Achieved HbA1c ≤ 6.5%, International Diabetes Federation (IDF) Target (Yes/no)(Week 26)
Participants Who Achieved HbA1c ≤ 6.5% and Change From Baseline in Body Weight Below or Equal to Zero(Week 26)
Change in Body Weight(Week 0, week 26)
Number of Treatment Emergent Severe or BG Confirmed Hypoglycaemic Episodes(Weeks 0-26)
Insulin Dose(Week 26)
Participants Who Achieved HbA1c <7.0% and Change in Body Weight From Baseline Below or Equal to Zero(Week 26)
Participants Who Achieved HbA1c ≤ 6.5% Without Severe or BG Confirmed Hypoglycaemic Episodes(Week 26)
9-point SMPG Profile(Week 26)
Change in Fasting C-peptide - Ratio to Baseline(Week 0, week 26)