A 38 Week Trial Comparing Effect and Safety of Insulin Degludec/Insulin Aspart vs. Insulin Glargine Plus Insulin Aspart in Subjects With Type 2 Diabetes Treated With Basal Insulin With or Without Oral Antidiabetic Treatment in Need of Treatment Intensification

Study Overview
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Brief Summary
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Trial comparing effect and safety of insulin degludec/insulin aspart vs. insulin glargine plus insulin aspart in subjects with type 2 diabetes treated with basal insulin with or without oral antidiabetic treatment in need of treatment intensification.

Official Title
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This Trial is Conducted Globally. The Aim of This Trial is to Compare the Effect and Safety of Insulin Degludec/Insulin Aspart vs. Insulin Glargine Plus Insulin Aspart in Subjects With Type 2 Diabetes Treated With Basal Insulin With or Without Oral Antidiabetic Treatment in Need of Treatment Intensification.

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin degludec/insulin aspart
* Drug: Insulin glargine
* Drug: Insulin aspart


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, age at least 18 years at the time of signing informed consent Algeria: Male or female, age at least 19 years at the time of signing informed consent Diagnosed with type 2 diabetes mellitus Treated with any basal insulin for at least 90 days prior to the day of screening Subject not on any OAD(s) prior to trial participation OR subjects on stable daily dose(s) of OAD(s) for at least 90 days prior to screening visit (V1). The OAD(s) include any of the following anti-diabetic drug s)/regimen: a. Biguanides (metformin at least 1500 mg or maximum tolerated dose documented in the subject medical record) b. Other OADs (at least half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record): i. Insulin secretagogues (SU and glinides) ii. Di-peptidyl-peptidase IV (DPP-4) inhibitors iii. α-glucosidase inhibitors iv. Sodium/glucose co-transporter 2 (SGLT-2) inhibitors v. Oral combination products (of the allowed individual OADs above) HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive) by central laboratory analysis Body mass index (BMI) equal to or below 45.0 kg/m^2 Exclusion Criteria: Participation in any clinical trial of an approved or non-approved investigational medicinal product within four weeks prior to the day of screening (V1) Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent severe metabolic dysregulation (e.g. diabetes ketoacidosis) equal or below 90 days prior to the day of the screening and between screening and randomisation Any of the following: myocardial infarction, stroke or hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and between screening and randomisation Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of below 60 ml/min/1.73 m^2 as defined by KDIGO 2012 classification using isotope dilution mass spectrometry (IDMS) for serum creatinine measured at screening Impaired liver function, defined as alanine aminotransferase (ALT) equal to or above 2.5 times upper normal limit (UNL) at screening. Subjects presently classified as being in New York Heart Association (NYHA) Class IV Planned coronary, carotid or peripheral artery revascularisation known on the day of screening Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids)

Ages Eligible for Study
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Minimum Age: 18 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: IDegAsp<br> | Drug: Insulin degludec/insulin aspart<br>* Administered subcutaneously (s.c. under the skin) once daily.<br>|
| Active Comparator: IGlar + IAsp<br> | Drug: Insulin glargine<br>* Administered subcutaneously (s.c. under the skin) once daily.<br>Drug: Insulin aspart<br>* 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 in HbA1c (%) - Week 26 | Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated 26 weeks after randomisation. | Week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (%) - Week 38 | Change from baseline (week 0) in HbA1c was evaluated 38 weeks after randomisation. | Week 0, week 38 | 
| Responder (Yes/No) for HbA1c < 7% | Participants achieving (yes/no) HbA1c <7% was evaluated 26 and 38 weeks after randomisation, respectively. | Week 26 and week 38 | 
| Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia | Participants achieving (yes/no) HbA1c <7% without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia, was evaluated 26 and 38 weeks after randomisation, respectively. Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Severe hypoglycaemia as per ADA classification: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. | Week 26 and week 38 | 
| Change in FPG | Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated 26 and 38 weeks after randomisation, respectively. | Week 0, week 26, week 38 | 
| Change in Pre-breakfast SMPG (Used for Titration) | Reported results are observed pre-breakfast self-measured plasma glucose (SMPG; used for titration) values at week 1 (baseline) and 26 and 38 weeks after randomisation. | Week 1, week 26, week 38 | 
| Change in Postprandial SMPG Increment (From 9-point Profile) | Change from baseline (week 0) in postprandial SMPG increment (from 9-point profile) was evaluated 26 and 38 weeks after randomisation, respectively. 9-point SMPG profiles were measured starting in the morning 2 days prior to the scheduled visit at the time points described below: 1) Before breakfast (2 days prior to visit) 2) 90 minutes after start of the breakfast 3) Before lunch 4) 90 minutes after start of the lunch 5) Before dinner/main evening meal 6) 90 minutes after start of the dinner/main evening meal 7) At bedtime (2 days or 1 day prior to visit depending on actual clock time) 8) At 4 a.m. (1 day prior to visit) 9) Before breakfast at the following day (1 day prior to the visit). | Week 0, week 26, week 38 | 
| Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Number of nocturnal, treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were analysed during the following periods: weeks 0-26, weeks 16-26 and weeks 0-38. Nocturnal hypoglycaemic episodes: episodes occurring between 00:01 and 05:59 both inclusive. Treatment emergent: hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. | Weeks 0-26, weeks 16-26, weeks 0-38 | 
| Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were analysed during the following periods: weeks 0-26, weeks 16-26 and weeks 0-38. Treatment emergent: hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. | Weeks 0-26, weeks 16-26, weeks 0-38 | 
| Total Insulin Dose | Total insulin dose was evaluated 26 and 38 weeks after randomisation, respectively. | Week 26 and week 38 | 
| Change in Body Weight | Change from baseline (week 0) in body weight was evaluated 26 and 38 weeks after randomisation, respectively. | Week 0, week 26, week 38 | 
| Incidence of TEAEs | Number of treatment emergent adverse events (TEAEs) were analysed during the following periods: weeks 0-26, weeks 26-38 and weeks 0-38. Treatment emergent: An adverse event that had an onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. If an event had an onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period, or if it had an onset date within 7 days after the last drug date, then this event was also to be considered as a TEAE. | Weeks 0-26, weeks 26-38, weeks 0-38 |