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

Phase 3

Completed

Conditions: Type 1 Diabetes Mellitus

Interventions: Drug: Fiasp®
Drug: Novolog®
Device: 670G hybrid closed loop continuous subcutaneous insulin infusion system

Registration Number: NCT03977727

Lead Sponsor: Texas Diabetes & Endocrinology, P.A.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Fiasp/Novolog	Fiasp®	7 weeks on Fiasp® then crossover to 7 weeks on Novolog® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion
Fiasp/Novolog	670G hybrid closed loop continuous subcutaneous insulin infusion system	7 weeks on Fiasp® then crossover to 7 weeks on Novolog® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion
Novolog/Fiasp	Fiasp®	7 weeks on Novolog® then crossover to 7 weeks on Fiasp® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion
Novolog/Fiasp	670G hybrid closed loop continuous subcutaneous insulin infusion system	7 weeks on Novolog® then crossover to 7 weeks on Fiasp® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion
Fiasp/Novolog	Novolog®	7 weeks on Fiasp® then crossover to 7 weeks on Novolog® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion
Novolog/Fiasp	Novolog®	7 weeks on Novolog® then crossover to 7 weeks on Fiasp® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion

Primary Outcome Measures

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

Secondary Outcome Measures

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