The Efficacy and Safety of Liraglutide Adjunct to Insulin Treatment in Type 1 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Africa, Europe and North America. The purpose of the trial is to investigate the efficacy and safety of liraglutide adjunct to insulin treatment in type 1 diabetes.

Official Title
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A 26-weeks Randomised, Insulin Capped, Placebo-controlled, Double-blind, Parallel Group, Multinational, Multi-centre Trial

Conditions
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Diabetes, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: liraglutide
* Drug: liraglutide
* Drug: liraglutide
* Drug: placebo
* Drug: placebo
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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 Male or female, aged equal to or greater than 18 years at the time of signing informed consent Type 1 diabetes mellitus (as diagnosed clinically) 12 months or longer prior to Visit 1 (i.e. screening) Treatment with basal bolus or CSII (continuous subcutaneous insulin infusion, insulin pump) treatment 6 months or longer prior to Visit 1 (i.e. screening) Stable insulin treatment 3 months or longer prior to Visit 1 (i.e. screening), as judged and documented by the investigator HbA1c 7.0-10.0 percent (Diabetes Control and Complications Trial (DCCT)), both inclusive, by central laboratory analysis (Visit 1, screening) corresponding to 53-86 mmol/mol (International Federation of Clinical Chemistry (IFCC)) Exclusion Criteria: Prior use of glucagon-like peptide-1 (GLP-1) receptor agonist or dipeptidyl peptidase IV (DPPIV) inhibitors Use of any medication, which in the investigator's opinion could interfere with the glycaemic control (e.g. systemic corticosteroids, pramlintide (Symlin®)) or affect the subject's safety. Premix insulin is not allowed Known proliferative retinopathy or maculopathy requiring acute treatment Severe neuropathy, in particular autonomic neuropathy, i.e. gastroparesis, as judged by the investigator Uncontrolled/untreated blood pressure at screening (Visit 1) (after resting for 5 minutes) while sitting greater than 160 mmHg for systolic or greater than 100 mmHg for diastolic (repeated measurement at Visit 2 (prior to performing the trial related activities) is allowed to exclude white-coat hypertension) History of acute or chronic pancreatitis Screening (Visit 1) calcitonin value equal to or greater than 50 ng/L

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide 1.8 mg + insulin<br> | Drug: liraglutide<br>* Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment will receive 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects will receive 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.<br>|
| Experimental: Liraglutide 1.2 mg + insulin<br> | Drug: liraglutide<br>* Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment will receive 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects will receive 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.<br>|
| Experimental: Liraglutide 0.6 mg + insulin<br> | Drug: liraglutide<br>* Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment will receive 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects will receive 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.<br>|
| Placebo Comparator: Liraglutide placebo 0.3 ml + insulin<br> | Drug: placebo<br>* Subjects randomised to 0.3 mL liraglutide placebo as an add-on to their pre-trial insulin treatment will receive 0.1 mL for 2 weeks followed by 0.2 mL for 2 weeks. After 4 weeks of liraglutide placebo, subjects will receive 0.3 mL for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.<br>|
| Placebo Comparator: Liraglutide placebo 0.2 ml + insulin<br> | Drug: placebo<br>* Subjects randomised to 0.3 mL liraglutide placebo as an add-on to their pre-trial insulin treatment will receive 0.1 mL for 2 weeks followed by 0.2 mL for 2 weeks. After 4 weeks of liraglutide placebo, subjects will receive 0.3 mL for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.<br>|
| Placebo Comparator: Liraglutide placebo 0.1 ml + insulin<br> | Drug: placebo<br>* Subjects randomised to 0.3 mL liraglutide placebo as an add-on to their pre-trial insulin treatment will receive 0.1 mL for 2 weeks followed by 0.2 mL for 2 weeks. After 4 weeks of liraglutide placebo, subjects will receive 0.3 mL for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Haemoglobin (HbA1c) | Change from baseline in glycosylated haemoglobin (HbA1c), after 26 weeks of treatment. Full analysis set (FAS = 831) included all randomised subjects who had received at least one dose and had any post-randomisation data. | Week 0, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Body Weight | Change from baseline body weight, after 26 weeks of treatment. Full analysis set (FAS = 831) included all randomised subjects who had received at least one dose and had any post-randomisation data. | Week 0, Week 26 | 
| Number of Treatment-emergent Symptomatic Hypoglycaemic Episodes | Number of treatment-emergent symptomatic hypoglycaemic episodes during 26 weeks of treatment. Symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification or a self-measured plasma glucose (SMPG) value of <3.1 mmol/L (56 mg/dL), with symptoms consistent with hypoglycaemia. Severe hypoglycaemia as per ADA classification is defined as an episode that required assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. | Weeks 0-26 |