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

• ClinicalTrials.gov Identifier: NCT03977727
• Recruitment Status: Completed
• First Posted: June 6, 2019
• Results First Posted: September 9, 2020
• Last Update Posted: September 29, 2020
• Sponsor: Texas Diabetes & Endocrinology, P.A.
• Information provided by (Responsible Party): Thomas C. Blevins, M.D., Texas Diabetes & Endocrinology, P.A.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes Mellitus	Drug: Fiasp®; Drug: Novolog®; Device: 670G hybrid closed loop continuous subcutaneous insulin infusion system	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: June 11, 2019
• Actual Primary Completion Date: March 9, 2020
• Actual Study Completion Date: April 20, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fiasp/Novolog; 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®; Fiasp® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system; Drug: Novolog®; Novolog® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system; Other Name: Aspart; Device: 670G hybrid closed loop continuous subcutaneous insulin infusion system; CSII; Other Name: Medtronic 670G pump
Experimental: Novolog/Fiasp; 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®; Fiasp® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system; Drug: Novolog®; Novolog® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system; Other Name: Aspart; Device: 670G hybrid closed loop continuous subcutaneous insulin infusion system; CSII; Other Name: Medtronic 670G pump

Outcome Measures

Primary Outcome Measures :

1. 1-Hour Change in Postprandial Plasma Glucose (PPG) [ Time Frame: 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 :

1. 2-Hour Change in Postprandial Plasma Glucose (PPG) [ Time Frame: 6th week of therapy ]
   Change was calculated as the value at 2 hour minus the value at baseline during meal test
2. Percentage of Time Spent Between Below 70 mg/dL [ Time Frame: 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)
3. Percentage of Time Spent Between 70 mg/dL and 180 mg/dL [ Time Frame: 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)
4. Percentage of Time Spent Above 200 mg/dL [ Time Frame: 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)
5. Percentage of Time Spent in Hypoglycemia (40 mg/dL - 54 mg/dL) [ Time Frame: 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)
6. Percentage of Time Spent in Severe Hypoglycemia (> 40 mg/dL) [ Time Frame: 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)
7. 1,5 Anhydroglucitol Levels [ Time Frame: Week 6, Week 13 ]
   1,5 anhydroglucitol levels were measured on the 6th week of each therapy
8. Fructosamine Levels [ Time Frame: Week 6, Week 13 ]
   Cumulative glycemic control expressed in fructosamine levels (micromol/Liter) were measured on the 6th week of each therapy
9. HbA1c [ Time Frame: Week 6, Week 13 ]
   Cumulative glycemic control expressed in HbA1c% measured on the 6th week of each therapy
10. Insulin Use - Change in Daily Dose [ Time Frame: 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
11. Insulin Use - Bolus [ Time Frame: 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
12. Insulin Use - Basal [ Time Frame: 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
13. Insulin Use - Automatic Basal Insulin [ Time Frame: Weeks 1 through 6, Weeks 8 through 13 ]
    Average amount per day (units) calculated for each participant under each therapy
14. Insulin Pump - Active Insulin Time [ Time Frame: Weeks 1 through 6, Weeks 8 through 13 ]
    Average time per day (hours) calculated for each participant under each therapy
15. Insulin Pump - Auto Mode [ Time Frame: Weeks 3 through 6, Weeks 10 through 13 ]
    Percentage of time spent in auto-mode after calibration under each therapy
16. Insulin Pump - Manual Mode [ Time Frame: Weeks 3 through 6, Weeks 10 through 13 ]
    Percentage of time spent in manual-mode after calibration under each therapy
17. Change in Carbohydrate Ratio [ Time Frame: 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
18. Infusion Site Reactions [ Time Frame: 14 week treatment period ]
    Number of Infusion site reactions reported by patient
19. Pump Occlusions [ Time Frame: 14 week treatment period ]
    Number of Occlusion events reported by patient

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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
2. Male or female, age ≥18 years at the time of signing informed consent
3. Documented diagnoses of T1DM ≥1 year prior to the day of screening
4. 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.
5. Ability and willingness to use the same insulin infusion sets throughout the trial
6. Using the same insulin for at least 30 days prior to screening
7. HbA1c < 8.5% as assessed by local laboratory at screening
8. BMI ≤ 35.0 kg/m2 at screening
9. 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:

1. Known or suspected hypersensitivity to trial products or related products
2. 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)
3. Participation in another clinical trial within 28 days before the screening visit. Note: clinical trials do not include non-interventional studies
4. Anticipated significant change in lifestyle (e.g. eating, exercise or sleeping pattern) throughout the trial
5. 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
6. Subjects classified as being in New York Heart Association (NYHA) Class IV at screening
7. Planned coronary, carotid or peripheral artery revascularization known on the day of screening.

8. Inadequately treated blood pressure defined as Grade 3 hypertension or higher (Systolic

   ≥180 mmHg or diastolic ≥110 mmHg) at screening

9. Impaired liver function, defined as ALT ≥ 2.5 times upper normal limit at screening
10. Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of < 45 ml/min/1.73 m2
11. 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
12. Proliferative retinopathy or maculopathy requiring acute treatment at the time of screening
13. History of hospitalization for ketoacidosis ≤180 days prior to the day of screening
14. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 30 days before screening
15. Presence of malignant neoplasms at the time of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed.
16. Reoccurring Severe hypoglycemia while on the Medtronic Minimed 670G in the investigators opinion

17. Any condition which, in the opinion of the Investigator, might jeopardize Subject's safety or compliance with the protocol

    -

Contacts and Locations

Locations

United States, Texas

Texas Diabetes & Endocrinology

Austin, Texas, United States, 78731

Sponsors and Collaborators

Texas Diabetes & Endocrinology, P.A.

Investigators

• Principal Investigator: Thomas Blevins, MD; Texas Diabetes & Endocrinology

  Study Documents (Full-Text)

Documents provided by Thomas C. Blevins, M.D., Texas Diabetes & Endocrinology, P.A.:

Study Protocol and Statistical Analysis Plan  [PDF] April 16, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ozer K, Cooper AM, Ahn LP, Waggonner CR, Blevins TC. Fast Acting Insulin Aspart Compared with Insulin Aspart in the Medtronic 670G Hybrid Closed Loop System in Type 1 Diabetes: An Open Label Crossover Study. Diabetes Technol Ther. 2021 Apr;23(4):286-292. doi: 10.1089/dia.2020.0500. Epub 2021 Mar 8.

• Responsible Party: Thomas C. Blevins, M.D., PI, Texas Diabetes & Endocrinology, P.A.
• ClinicalTrials.gov Identifier: NCT03977727
• Other Study ID Numbers: U1111-1213-9104
• First Posted: June 6, 2019
• Results First Posted: September 9, 2020
• Last Update Posted: September 29, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Insulin Aspart; Hypoglycemic Agents; Physiological Effects of Drugs