Safety and Efficacy of Insulin Degludec/Insulin Aspart in Patients With T1DM

Study Overview
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Brief Summary
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In this prospective, randomized, open-label, parallel group trial, the safety and efficacy of insulin degludec/insulin aspart (IDegAsp) twice daily will be compared with basal insulin once or twice daily plus pre-prandial insulin after 16 weeks of treatment in patients with type 1 diabetes. This trial will enable assessment of the clinically relevant endpoint of a change in HbA1c and Time in Range (TIR).

Detailed Description
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The objective of the current study is to investigate the efficacy and safety of IDegAsp twice daily compared to basal insulin once or twice daily plus pre-prandial insulin for 16 weeks in patients with type 1 diabetes mellitus. The primary endpoint in this study is the change from baseline in HbA1c. Patients with type 1 diabetes who meet the entry criteria are planned for inclusion in this trial. Approximately 40 patients will be enrolled in the study. Patients who qualify will be randomized to IDegAsp group or basal plus pre-prandial insulin group. Duration of treatment includes 2-week screening period, 16-week treatment observation period and 1-week follow-up.

Official Title
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A Prospective, Randomized, Open-label, Parallel Group Study to Evaluate Safety and Efficacy of Insulin Degludec/Insulin Aspart in Patients With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus With Diabetic Gastroparesis, HbA1c, Time in Range

Intervention / Treatment
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* Drug: insulin degludec/insulin aspart (IDegAsp)
* Drug: basal insulin plus pre-prandial insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 and ≤75 years with type 1 diabetes; Diagnosed as T1DM ≥ 12 months before enrollment in the study; HbA1c ≥ 7.0 to ≤10.0%; Receipt of basal plus pre-prandial insulin and/or oral anti-diabetic agents ≥ 12 weeks before enrollment in the study; BMI ≤ 35kg / m2. Exclusion Criteria: Patients with any of the following conditions will be excluded: Pregnant or lactating women Severe hypoglycemia within one month; Myocardial infarction, stroke or other severe cardiovascular events within 6 months prior to informed consent Receipt of Sulfonylureas, Meglitinides derivatives, Thiazolidinediones, Dpp-4 inhibitors or GLP-1 agonists within 3 months prior to informed consent; Current treatment with systemic steroids or immunosuppressive agents, or have immunologic deficiency disease at time of informed consent Severe mental instability, or alcohol abuse, or drug abuse Cancer within 5 years prior to informed consent Pancreatitis of severe infectious diseases within 1 months prior to informed consent Known hypersensitivity or allergy to the insulin Renal impairment (CKD-EPI eGFR<60ml/min) Impaired hepatic function, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined Participation in another trial within 2 months prior to informed consent Patients that investigators believe may fail to complete the study

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: IDegAsp group<br>IDegAsp twice daily | Drug: insulin degludec/insulin aspart (IDegAsp)<br>* To evaluate the efficacy and safety of the IDegAsp in T1DM<br>* Other names: Ryzodeg;|
| Active Comparator: basal insulin plus pre-prandial insulin group<br>basal insulin once or twice daily plus pre-prandial insulin | Drug: basal insulin plus pre-prandial insulin<br>* To evaluate the efficacy and safety of basal insulin plus pre-prandial insulin in T1DM<br>* Other names: Levemir/Lantus/Tresiba plus NovoLog/Humalog/Apidra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c | the change from baseline in HbA1c after 16 weeks of treatment in all patients | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time In Range (TIR) | The change from baseline in Time in Range (3.9-10mmol/L) after 16 weeks of treatment in all patients (using flash continuous glucose monitoring (FCGM)). | 16 weeks | 
| Time to occurrence of treat to target | Fasting glucose on treatment <7mmol/L and non-fasting glucose <10mmol/L, or TIR >70%) (SMBG or FCGM) | 16 weeks | 
| Occurrence of a treat to target response and without any hypoglycemic episodes | Occurrence of a treat to target response and without any hypoglycemic episodes | 16 weeks | 
| EQ-5D Health Questionnaire | the EQ-5D descriptive system The change from baseline after 16 weeks of treatment | 16 weeks | 
| Short Form 36 (SF-36) | The change from baseline after 16 weeks of treatment | 16 weeks | 
| Insulin dose | The change from baseline after 16 weeks of treatment | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes, insulin degludec/insulin aspart, HbA1c, Time in Range