FIasp® vs. Novolog® in Type 1 Diabetics Using 670G Medtronic Pump

Study Overview
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Brief Summary
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This is an exploratory, single-center, randomized, open label, active-controlled, complete cross-over trial comparing safety and efficacy of Fiasp® versus NovoLog® when used in the Medtronic MiniMed 670G system in subjects with T1DM.

Detailed Description
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This study is being performed to compare Fiasp® in terms of glycemic control with a focus on post-prandial 1-hour plasma glucose level and system-based outcomes to NovoLog® insulin when used in the Medtronic mini Med 670G HCL system (operating in auto-mode) in patients with type 1 diabetes. The investigator's hypothesis is that post prandial glucoses will be lower and time in range will be greater during the Fiasp® treatment period. Subjects will have a 2 week screening period, 14 week treatment period and 30 Day follow up period. After at least 7 weeks on treatment period one they will crossover to treatment period two on the opposite treatment for 7 additional weeks.

Official Title
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An Exploratory, Single-center, Randomized, Open Label, Active-control, Cross-over Trial Comparing the Efficacy and Safety of Continuous Subcutaneous Insulin Infusion of Faster-acting Insulin Aspart (Fiasp®) Compared to NovoLog® Used in the Medtronic 670G Closed Loop System in Adults With Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Fiasp®
* Drug: Novolog®
* Device: 670G hybrid closed loop continuous subcutaneous insulin infusion system


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 ≥18 years at the time of signing informed consent Documented diagnoses of T1DM ≥1 year prior to the day of screening Using the Medtronic pump Minimed 670G for CSII in a basal-bolus regimen with a rapid acting insulin analogue for at least 30 days prior to screening and willing to continue using their personal Medtronic Minimed 670G and CSII for insulin treatment throughout the trial. Ability and willingness to use the same insulin infusion sets throughout the trial Using the same insulin for at least 30 days prior to screening HbA1c < 8.5% as assessed by local laboratory at screening BMI ≤ 35.0 kg/m2 at screening Ability and willingness to adhere to the protocol including performing SMPG profiles, attending visits, utilizing the auto mode feature of the pump for at least 80 % of the time during the study, and completing meal tests Exclusion Criteria: Known or suspected hypersensitivity to trial products or related products Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice) Participation in another clinical trial within 28 days before the screening visit. Note: clinical trials do not include non-interventional studies Anticipated significant change in lifestyle (e.g. eating, exercise or sleeping pattern) throughout the trial Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischemic attack within the past 180 days prior to the day of screening Subjects classified as being in New York Heart Association (NYHA) Class IV at screening Planned coronary, carotid or peripheral artery revascularization known on the day of screening. Inadequately treated blood pressure defined as Grade 3 hypertension or higher (Systolic ≥180 mmHg or diastolic ≥110 mmHg) at screening Impaired liver function, defined as ALT ≥ 2.5 times upper normal limit at screening Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of < 45 ml/min/1.73 m2 Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism in the opinion of the Investigator Proliferative retinopathy or maculopathy requiring acute treatment at the time of screening History of hospitalization for ketoacidosis ≤180 days prior to the day of screening Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 30 days before screening Presence of malignant neoplasms at the time of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed. Reoccurring Severe hypoglycemia while on the Medtronic Minimed 670G in the investigators opinion Any condition which, in the opinion of the Investigator, might jeopardize Subject's safety or compliance with the protocol -

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fiasp/Novolog<br>7 weeks on Fiasp® then crossover to 7 weeks on Novolog® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion | Drug: Fiasp®<br>* Fiasp® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system<br>Drug: Novolog®<br>* Novolog® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system<br>* Other names: Aspart;Device: 670G hybrid closed loop continuous subcutaneous insulin infusion system<br>* CSII<br>* Other names: Medtronic 670G pump;|
| Experimental: Novolog/Fiasp<br>7 weeks on Novolog® then crossover to 7 weeks on Fiasp® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion | Drug: Fiasp®<br>* Fiasp® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system<br>Drug: Novolog®<br>* Novolog® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system<br>* Other names: Aspart;Device: 670G hybrid closed loop continuous subcutaneous insulin infusion system<br>* CSII<br>* Other names: Medtronic 670G pump;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-Hour Change in Postprandial Plasma Glucose (PPG) | Change was calculated as the PPG value at 1 hour minus the PPG value at baseline (time -2 minutes) during meal test | 6th week of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-Hour Change in Postprandial Plasma Glucose (PPG) | Change was calculated as the value at 2 hour minus the value at baseline during meal test | 6th week of therapy | 
| Percentage of Time Spent Between Below 70 mg/dL | Percent of time spent is calculated as the accumulated time in hours spent within each range divided by the total number of hours spent under therapy with each drug (6 weeks each) | Weeks 1 through 6, Weeks 8 through 13 | 
| Percentage of Time Spent Between 70 mg/dL and 180 mg/dL | Percent of time spent is calculated as the accumulated time in hours spent within each range divided by the total number of hours spent under therapy with each drug (6 weeks each) | Weeks 1 through 6, Weeks 8 through 13 | 
| Percentage of Time Spent Above 200 mg/dL | Percent of time spent is calculated as the accumulated time in hours spent within each range divided by the total number of hours spent under therapy with each drug (6 weeks each) | Weeks 1 through 6, Weeks 8 through 13 | 
| Percentage of Time Spent in Hypoglycemia (40 mg/dL - 54 mg/dL) | Percent of time spent is calculated as the accumulated time in hours spent within each range divided by the total number of hours spent under therapy with each drug (6 weeks each) | Weeks 1 through 6, Weeks 8 through 13 | 
| Percentage of Time Spent in Severe Hypoglycemia (> 40 mg/dL) | Percent of time spent is calculated as the accumulated time in hours spent within each range divided by the total number of hours spent under therapy with each drug (6 weeks each) | Weeks 1 through 6, Weeks 8 through 13 | 
| 1,5 Anhydroglucitol Levels | 1,5 anhydroglucitol levels were measured on the 6th week of each therapy | Week 6, Week 13 | 
| Fructosamine Levels | Cumulative glycemic control expressed in fructosamine levels (micromol/Liter) were measured on the 6th week of each therapy | Week 6, Week 13 | 
| HbA1c | Cumulative glycemic control expressed in HbA1c% measured on the 6th week of each therapy | Week 6, Week 13 | 
| Insulin Use - Change in Daily Dose | Change was calculated as the value on the last day of therapy minus the value on the 1st day of therapy in each period | Weeks 1 through 6, Weeks 8 through 13 | 
| Insulin Use - Bolus | Change in %bolus insulin (units) as the value on the last day of therapy minus the value on the 1st day of therapy in each period | Weeks 1 through 6, Weeks 8 through 13 | 
| Insulin Use - Basal | Change in %basal insulin (units) as the value on the last day of therapy minus the value on the 1st day of therapy in each period | Weeks 1 through 6, Weeks 8 through 13 | 
| Insulin Use - Automatic Basal Insulin | Average amount per day (units) calculated for each participant under each therapy | Weeks 1 through 6, Weeks 8 through 13 | 
| Insulin Pump - Active Insulin Time | Average time per day (hours) calculated for each participant under each therapy | Weeks 1 through 6, Weeks 8 through 13 | 
| Insulin Pump - Auto Mode | Percentage of time spent in auto-mode after calibration under each therapy | Weeks 3 through 6, Weeks 10 through 13 | 
| Insulin Pump - Manual Mode | Percentage of time spent in manual-mode after calibration under each therapy | Weeks 3 through 6, Weeks 10 through 13 | 
| Change in Carbohydrate Ratio | Change was calculated as the carbohydrate ratio on the last day of therapy minus the carbohydrate ratio on the 1st day of therapy in each period | Weeks 1 through 6, Weeks 8 through 13 | 
| Infusion Site Reactions | Number of Infusion site reactions reported by patient | 14 week treatment period | 
| Pump Occlusions | Number of Occlusion events reported by patient | 14 week treatment period |