A Double-blinded Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide and Insulin Degludec Both in Combination With Metformin in Japanese Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Basal or Pre-mix/Combination Insulin Therapy and Oral Anti-diabetic Drugs

Novo Nordisk A/S1 site in 1 country210 target enrollmentSeptember 21, 2016

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: 210
Locations: 1
Primary Endpoint: Change in Glycosylated Haemoglobin (HbA1c)
Status: Completed
Last Updated: 5 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 compare the efficacy and safety of insulin degludec/liraglutide and insulin degludec both in combination with metformin in Japanese subjects with type 2 diabetes mellitus inadequately controlled with basal or pre-mix/combination insulin therapy and oral anti-diabetic drugs.

Registry

clinicaltrials.gov

Start Date

September 21, 2016

End Date

November 22, 2017

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novo Nordisk A/S

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female Japanese subjects, age at least 20 years at the time of signing informed consent
•T2DM (type 2 diabetes mellitus) subjects (diagnosed clinically) for at least 6 months prior to screening
•HbA1c (glycosylated haemoglobin) 7.5-11.0 per cent \[58 mmol/mol-97 mmol/mol\] (both inclusive) by central laboratory analysis
•Subjects on stable daily insulin doses for at least 60 days prior to screening administered once or twice daily, either as basal insulin (e.g. IDeg, insulin glargine, insulin detemir, NPH insulin) or pre-mix/combination insulin (e.g. biphasic insulin aspart, insulin degludec/insulin aspart). Total daily insulin dose in the previous 60 days should be within 20-50 units, both inclusive, and on the day of screening, but fluctuations of plus/minus 20 per cent within the 60 days prior to screening are acceptable. The specified insulin treatment should be administered in combination with a stable daily dose of metformin within current approved Japanese label for at least 60 days prior to screening - additionally, the anti-diabetic treatment can be with or without a stable daily dose of one of the following other OADs (oral anti-diabetic drug): SU (sulfonylureas), glinides, alpha-glucosidase inhibitor, SGLT2i (sodium glucose co-transporter 2 inhibitor) or TZD (thiazolidinedione) within current approved Japanese label for at least 60 days prior to screening
•Body Mass Index (BMI) equal or above 23 kg/m\^2

Exclusion Criteria

•Receipt of any investigational medicinal product (IMP) within 30 days before screening
•Use of any anti-diabetic drug in a period of 60 days before screening (except premix/ combination or basal insulin, metformin, SU, glinides, α-GI, SGLT2i, or TZD) or anticipated change in concomitant medication, which in the investigators opinion could interfere with glucose metabolism (e.g. systemic corticosteroids or bolus insulin)
•Treatment with glucagon-like peptide-1 (GLP-1) receptor agonist during the last 60 days prior to screening and furthermore, the discontinuation of GLP-1 receptor agonist at any point in time must not have been due to safety concerns, tolerability issues or lack of efficacy, as judged by the investigator
•Treatment with dipetidyl peptidase-4 (DPP-4) inhibitors during the last 60 days prior to screening - Impaired liver function, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal or above 2.5 times upper limit of normal
•Renal impairment estimated Glomerular Filtration Rate (eGFR) below 60 mL/min/1.73m\^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
•Screening calcitonin equal or above 50 ng/L
•History of pancreatitis (acute or chronic)
•Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2)
•Subjects presently classified as being in New York Heart Association (NYHA) Class IV

Arms & Interventions

Insulin degludec/liraglutide

Intervention: Insulin degludec/liraglutide

Insulin degludec

Intervention: Insulin degludec

Outcomes

Primary Outcomes

Change in Glycosylated Haemoglobin (HbA1c)

Time Frame: week 0, week 26

Change from baseline (week 0) in HbA1c after 26 weeks of treatment.

Secondary Outcomes

Change in Body Weight(week 0, week 26)
Responder (Yes/no): HbA1c Less Than 7.0% and Without Weight Gain(After 26 weeks)
Responder (Yes/no): HbA1c Less Than 7.0% and Without Weight Gain and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment(After 26 weeks)
Responder (Yes/no): HbA1c Less Than 7.0%(After 26 weeks)
Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes(During 26 weeks of treatment)
Responder (Yes/no): HbA1c Less Than 7.0% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment(After 26 weeks)
Change in Pulse(Week 0, week 26)
Responder (Yes/no): HbA1c Less Than or Equal to 6.5%(After 26 weeks)
Change in Fasting Plasma Glucose (FPG)(week 0, week 26)
Daily Insulin Dose(After 26 weeks)
Change in Waist Circumference(week 0, week 26)
Number of Treatment Emergent Adverse Events (TEAE)(During 26 weeks of treatment)
Responder (Yes/no): HbA1c Less Than or Equal to 6.5% Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment(After 26 weeks)
Change in SMBG 9-point Profile: Mean of the 9-point Profile(Week 0, week 26)
Change From Baseline in Patient Reported Outcomes (PROs) of Treatment: Diabetes Therapy-Related Quality of Life (DTR-QOL)Questionnaire(week 0, week 26)
Change From Baseline in Patient Reported Outcomes (PROs) of Treatment: EuroQol-5D (EQ-5D-5L) Questionnaire(week 0, week 26)
Responder (Yes/no): HbA1c Less Than or Equal to 6.5% and Without Weight Gain(After 26 weeks)
Responder (Yes/no): HbA1c Less Than or Equal to 6.5% and Without Weight Gain and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment(After 26 weeks)
Change in Blood Pressure (Systolic and Diastolic)(week 0, week 26)
Self-measured Blood Glucose (SMBG) 9-point Profile (Individual Points in the Profile)(After 26 weeks)
Change in SMBG 9-point Profile: Mean of Postprandial Plasma Glucose Increments (From Before Meal to 90 Minutes After Breakfast, Lunch and Dinner)(Week 0, week 26)
Fasting Lipid Profile(Week 0, week 26)
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes(During 26 weeks of treatment)
Number of Treatment Emergent Hypoglycaemic Episodes According to American Diabetes Association (ADA) Definition(During 26 weeks of treatment)
Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes(During 26 weeks of treatment)
Change in Clinical Evaluation: Fundoscopy or Fundus Photography(Screening (week -2 to week 0), week 26)
Change in Clinical Evaluation: Electrocardiogram (ECG)(Screening (week -2 to week 0), week 26)