A Research Study in People With Type 2 Diabetes to Compare Two Types of Insulin: Insulin 287 and Insulin Glargine

Study Overview
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Brief Summary
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This study compares insulin 287 (a possible new medicine) to insulin glargine (a medicine doctors can already prescribe) in people with type 2 diabetes. Different ways of switching from the insulin which the participants are already on to insulin 287 are also compared. This is done to find the best way to switch to insulin 287. The participants will either get insulin 287 that they will have to inject once a week or insulin glargine that they will have to inject once a day. Which treatment any participant gets is decided by chance. The study will last for about 5 months (23 weeks). The participants will have 14 clinic visits and 6 phone calls with the study doctor. At 3 of the clinic visits participants will be asked not to eat or drink anything (except for water) in the last 8 hours before the visit. During the study, the doctor will ask the participants to: 1) measure their blood sugar every day with a blood sugar meter using a finger prick; 2) write down different information in a diary daily and return this to their study doctor. 3) wear a medical device (sensor) that measures the participants blood sugar all the time for 18 weeks (about 4 months) during the study.

Official Title
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A Trial Comparing NNC0148-0287 C (Insulin 287) Versus Insulin Glargine U100, Both in Combination With Metformin, With or Without DPP4 Inhibitors and With or Without SGLT2 Inhibitors, in Basal Insulin Treated Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin icodec
* Drug: Insulin glargine U100


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent. Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening. Glycosylated haemoglobin (HbA1c) of 7.0-10.0% (53.0-85.8 mmol/mol) (both inclusive) as assessed by central laboratory. Treated with once daily or twice daily basal insulin analogue (insulin degludec, insulin detemir, insulin glargine U100 or U300, total daily dose of 10-50 U, both inclusive) greater than or equal to 90 days prior to the day of screening. Stable daily dose(s) for 90 days prior to the day of screening of any of the following antidiabetic drug(s) or combination regime(s): Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject's medical records). Free or fixed combination therapy: Metformin as outlined above with or without dipeptidyl peptidase 4 inhibitors (DPP4i) with or without sodium-glucose cotransporter 2 inhibitors (SGLT2i) is allowed: 1) DPP4i (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose); 2) SGLT2i (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose. Body mass index (BMI) less than or equal to 40.0 kg/m^2. Exclusion criteria: Known or suspected hypersensitivity to trial product(s) or related products. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method. Participation in any clinical trial of an approved or non-approved investigational medicinal product within 90 days before screening. Any disorder, except for conditions associated with type 2 diabetes mellitus, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol. Any episodes of diabetic ketoacidosis within the past 90 days prior to the day of screening and between screening and randomisation. Known hypoglycaemic unawareness as indicated by the Investigator according to Clarke's questionnaire question 8. Recurrent severe hypoglycaemic episodes within the last year as judged by the Investigator. Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening and between screening and randomisation.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin 287 (with 100% loading dose)<br>Participants will receive insulin 287 injections once weekly (OW). A unit to unit switch approach with an additional 100% loading dose of insulin 287 will be used. | Drug: Insulin icodec<br>* Participants will receive subcutaneous (s.c.) injections of Insulin 287 OW for 16 weeks.<br>* Other names: Insulin 287;|
| Experimental: Insulin 287 (without loading dose)<br>Participants will receive insulin 287 injections OW. A unit to unit switch approach without loading dose of insulin 287 will be used. | Drug: Insulin icodec<br>* Participants will receive subcutaneous (s.c.) injections of Insulin 287 OW for 16 weeks.<br>* Other names: Insulin 287;|
| Active Comparator: Insulin glargine U100<br>Participants will receive insulin glargine U100 once daily (OD). | Drug: Insulin glargine U100<br>* Participants will receive s.c. injections of insulin glargine OD for 16 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Time in Target Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter (mg/dL)) Measured Using CGM (Continuous Glucose Monitoring) | The percentage of time spent in glycaemic target range was calculated as 100 times the number of recorded measurements in glycaemic target range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive divided by the total number of recorded measurements. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). | During the last 2 weeks of treatment (week 15 and 16) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin (HbA1c) | Estimated mean change from baseline (week 0) in HbA1c at week 16 is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). | From baseline week 0 (V2) to week 16 (V18) | 
| Change in Fasting Plasma Glucose (FPG) | Estimated mean change from baseline (week 0) in FPG at week 16 is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). | From baseline week 0 (V2) to week 16 (V18) | 
| Change in Body Weight | Estimated mean change from baseline (week 0) in body weight at week 16 is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). | From baseline week 0 (V2) to week 16 (V18) | 
| Weekly Insulin Dose | Estimated mean average weekly insulin dose during the last 2 weeks of treatment is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). | During the last 2 weeks of treatment (week 15 and 16) | 
| Number of Treatment-emergent Adverse Events (TEAEs) | An adverse event(AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage.. A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The on-treatment observation period was the time period from first dose of trial product until the follow-up visit or the last date on trial product + 5 weeks for once daily insulin and +6 weeks for once weekly insulin. Safety analysis set (SAS) included all subjects exposed to at least one dose of trial product. | From baseline week 0 (V2) to week 21 (V20) | 
| Number of Severe Hypoglycaemic Episodes (Level 3) | Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred during weeks 0-16 are presented. | From baseline week 0 (V2) to week 16 (V18) | 
| Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3) | Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of <3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG)meter or severe hypoglycaemic episodes (level 3) that occured during weeks 0-16 are presented. | From baseline week 0 (V2) to week 16 (V18) | 
| Number of Hypoglycaemic Alert Episodes(Level 1) (Greater Than or Equal to 3.0 and Below 3.9 mmol/L (Greater Than or Equal to 54 and Below 70 mg/dL), Confirmed by BG Meter) | Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy. Number of hypoglycaemic alert episodes (level 1) (equal to or above 3.0 and below 3.9 mmol/L (equal to or above 54 and below 70 mg/dL), confirmed by BG meter) that occured during weeks 0-16 are presented. | From baseline week 0 (V2) to week 16 (V18) |