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

• Sponsor: Texas Diabetes & Endocrinology, P.A. (Other)
• Overall Status: Completed
• CT.gov ID: NCT03977727
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 2
• Actual Duration (Months): 10.3
• Patients Per Site Per Month: 3.9

Study Details

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
• 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: Jun 11, 2019
• Actual Primary Completion Date: Mar 9, 2020
• Actual Study Completion Date: Apr 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 Names: Aspart ; Device: 670G hybrid closed loop continuous subcutaneous insulin infusion system; CSII; Other Names: 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 Names: Aspart ; Device: 670G hybrid closed loop continuous subcutaneous insulin infusion system; CSII; Other Names: Medtronic 670G pump

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. 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)

3. 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)

4. 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)

5. 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)

6. 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)

7. 1,5 Anhydroglucitol Levels [Week 6, Week 13]

   1,5 anhydroglucitol levels were measured on the 6th week of each therapy

8. Fructosamine Levels [Week 6, Week 13]

   Cumulative glycemic control expressed in fructosamine levels (micromol/Liter) were measured on the 6th week of each therapy

9. HbA1c [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 [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 [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 [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 [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 [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 [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 [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 [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 [14 week treatment period]

    Number of Infusion site reactions reported by patient

19. Pump Occlusions [14 week treatment period]

    Number of Occlusion events reported by patient

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. Impaired liver function, defined as ALT ≥ 2.5 times upper normal limit at screening

2. Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of < 45 ml/min/1.73 m2

3. 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

4. Proliferative retinopathy or maculopathy requiring acute treatment at the time of screening

5. History of hospitalization for ketoacidosis ≤180 days prior to the day of screening

6. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 30 days before screening

7. Presence of malignant neoplasms at the time of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed.

8. Reoccurring Severe hypoglycemia while on the Medtronic Minimed 670G in the investigators opinion

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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)

• Study Protocol and Statistical Analysis Plan - Apr 16, 2019

More Information

Publications

None provided.

• 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: Jun 6, 2019
• Last Update Posted: Sep 29, 2020
• Last Verified: Aug 1, 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; Insulin Aspart

Study Results

Participant Flow

Recruitment Details	45 patients were screened for eligibility between June 11,2019 and November 21, 2019 at a diabetes clinic in Austin, TX
Pre-assignment Detail	40 of 45 participants were randomized. All 5 who were not randomized did not meet inclusion criteria.

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	7 weeks on Fiasp® then crossover to 7 weeks on Novolog® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion Fiasp®: Fiasp® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system Novolog®: Novolog® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system 670G hybrid closed loop continuous subcutaneous insulin infusion system: CSII	7 weeks on Novolog® then crossover to 7 weeks on Fiasp® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion Fiasp®: Fiasp® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system Novolog®: Novolog® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system 670G hybrid closed loop continuous subcutaneous insulin infusion system: CSII
Period Title: First Treatment
STARTED	20	20
Received Treatment	20	20
COMPLETED	20	20
NOT COMPLETED	0	0
Period Title: First Treatment
STARTED	20	20
COMPLETED	20	17
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp	Total
Arm/Group Description	7 weeks on Fiasp® then crossover to 7 weeks on Novolog® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion Fiasp®: Fiasp® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system Novolog®: Novolog® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system 670G hybrid closed loop continuous subcutaneous insulin infusion system: CSII	7 weeks on Novolog® then crossover to 7 weeks on Fiasp® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion Fiasp®: Fiasp® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system Novolog®: Novolog® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system 670G hybrid closed loop continuous subcutaneous insulin infusion system: CSII	Total of all reporting groups
Overall Participants	20	17	37
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.2 (13.17)	43.8 (12.77)	45.7 (27.1)
Sex: Female, Male (Count of Participants)
Female	8 40%	4 23.5%	12 32.4%
Male	12 60%	13 76.5%	25 67.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5%	1 5.9%	2 5.4%
Not Hispanic or Latino	19 95%	16 94.1%	35 94.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	20 100%	17 100%	37 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	20 100%	17 100%	37 100%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.9 (3.69)	27.3 (3.15)	27.1 (3.41)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	80.3 (14.7)	83.3 (12.45)	81.7 (13.61)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	172.3 (10.82)	174.6 (7.22)	173.4 (9.29)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each arm

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	105.15 (56.73)	154.24 (54.25)
NovoLog	99.90 (82.70)	114.94 (61.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fiasp/Novolog, Novolog/Fiasp
	Comments	Linear mixed model was fit with therapy (Fiasp vs. NovoLog), period (Period 1 vs Period 2), and sequence (Fiasp/NovoLog vs NovoLog/Fiasp) as fixed effects. Subjects included as random effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.008
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	27.35
	Confidence Interval	(2-Sided) 95%; 7.88 to 48.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each arm

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	72.55 (90.62)	65.00 (57.22)
NovoLog	69.10 (92.55)	104.53 (80.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fiasp/Novolog, Novolog/Fiasp
	Comments	Linear mixed model was fit with therapy (Fiasp vs. NovoLog), period (Period 1 vs Period 2), and sequence (Fiasp/NovoLog vs NovoLog/Fiasp) as fixed effects. Subjects included as random effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.136
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15.22
	Confidence Interval	(2-Sided) 95%; -5.42 to 39.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Time Spent Between Below 70 mg/dL
Description	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)
Time Frame	Weeks 1 through 6, Weeks 8 through 13

Outcome Measure Data

Analysis Population Description

All patients for whom continuous glucose monitoring data was available during the specified time periods

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	1.94 (1.48)	1.72 (1.20)
NovoLog	2.42 (1.62)	2.03 (1.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fiasp/Novolog, Novolog/Fiasp
	Comments	Linear mixed model was fit with therapy (Fiasp vs. NovoLog), period (Period 1 vs Period 2), and sequence (Fiasp/NovoLog vs NovoLog/Fiasp) as fixed effects. Subjects included as random effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.029
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	.4
	Confidence Interval	(2-Sided) 95%; .05 to .73
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Time Spent Between 70 mg/dL and 180 mg/dL
Description	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)
Time Frame	Weeks 1 through 6, Weeks 8 through 13

Outcome Measure Data

Analysis Population Description

All patients for whom continuous glucose monitoring data was available during the specified time periods

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	74.80 (8.08)	73.67 (6.80)
NovoLog	70.28 (8.12)	75.04 (5.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fiasp/Novolog, Novolog/Fiasp
	Comments	Linear mixed model was fit with therapy (Fiasp vs. NovoLog), period (Period 1 vs Period 2), and sequence (Fiasp/NovoLog vs NovoLog/Fiasp) as fixed effects. Subjects included as random effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.016
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.81
	Confidence Interval	(2-Sided) 95%; -2.84 to -0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Time Spent Above 200 mg/dL
Description	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)
Time Frame	Weeks 1 through 6, Weeks 8 through 13

Outcome Measure Data

Analysis Population Description

All patients for whom continuous glucose monitoring data was available during the specified time periods

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	14.90 (6.90)	15.44 (5.65)
NovoLog	18.57 (7.85)	14.11 (4.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fiasp/Novolog, Novolog/Fiasp
	Comments	Linear mixed model was fit with therapy (Fiasp vs. NovoLog), period (Period 1 vs Period 2), and sequence (Fiasp/NovoLog vs NovoLog/Fiasp) as fixed effects. Subjects included as random effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.045
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 95%; .04 to 2.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Time Spent in Hypoglycemia (40 mg/dL - 54 mg/dL)
Description	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)
Time Frame	Weeks 1 through 6, Weeks 8 through 13

Outcome Measure Data

Analysis Population Description

All patients for whom continuous glucose monitoring data was available during the specified time periods

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	.46 (.53)	.40 (.48)
NovoLog	.50 (.50)	.35 (.36)

7. Secondary Outcome

Title	Percentage of Time Spent in Severe Hypoglycemia (> 40 mg/dL)
Description	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)
Time Frame	Weeks 1 through 6, Weeks 8 through 13

Outcome Measure Data

Analysis Population Description

All patients for whom continuous glucose monitoring data was available during the specified time periods

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	0 (0)	0 (0)
NovoLog	0 (0)	0 (0)

8. Secondary Outcome

Title	1,5 Anhydroglucitol Levels
Description	1,5 anhydroglucitol levels were measured on the 6th week of each therapy
Time Frame	Week 6, Week 13

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each period

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	6.50 (3.37)	7.12 (3.23)
NovoLog	6.28 (3.54)	6.95 (3.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fiasp/Novolog, Novolog/Fiasp
	Comments	Linear mixed model was fit with therapy (Fiasp vs. NovoLog), period (Period 1 vs Period 2), and sequence (Fiasp/NovoLog vs NovoLog/Fiasp) as fixed effects. Subjects included as random effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.303
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-.2
	Confidence Interval	(2-Sided) 95%; -.59 to .16
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Fructosamine Levels
Description	Cumulative glycemic control expressed in fructosamine levels (micromol/Liter) were measured on the 6th week of each therapy
Time Frame	Week 6, Week 13

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each period

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	322.60 (42.24)	296.35 (31.10)
NovoLog	305.40 (32.28)	314.31 (28.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fiasp/Novolog, Novolog/Fiasp
	Comments	Linear mixed model was fit with therapy (Fiasp vs. NovoLog), period (Period 1 vs Period 2), and sequence (Fiasp/NovoLog vs NovoLog/Fiasp) as fixed effects. Subjects included as random effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.968
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.18
	Confidence Interval	(2-Sided) 95%; -10.32 to 9.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	HbA1c
Description	Cumulative glycemic control expressed in HbA1c% measured on the 6th week of each therapy
Time Frame	Week 6, Week 13

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each period

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	7.09 (.47)	7.00 (.31)
NovoLog	7.09 (.44)	6.88 (.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fiasp/Novolog, Novolog/Fiasp
	Comments	Linear mixed model was fit with therapy (Fiasp vs. NovoLog), period (Period 1 vs Period 2), and sequence (Fiasp/NovoLog vs NovoLog/Fiasp) as fixed effects. Subjects included as random effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.059
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-.06
	Confidence Interval	(2-Sided) 95%; -.13 to 0
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Insulin Use - Change in Daily Dose
Description	Change was calculated as the value on the last day of therapy minus the value on the 1st day of therapy in each period
Time Frame	Weeks 1 through 6, Weeks 8 through 13

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each arm

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	-2.1 (7.45)	.29 (13.35)
NovoLog	1.10 (11.80)	-2.65 (9.13)

12. Secondary Outcome

Title	Insulin Use - Bolus
Description	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
Time Frame	Weeks 1 through 6, Weeks 8 through 13

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each arm

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	-1.54 (6.54)	-4.32 (7.85)
NovoLog	1.83 (7.62)	-1.34 (5.35)

13. Secondary Outcome

Title	Insulin Use - Basal
Description	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
Time Frame	Weeks 1 through 6, Weeks 8 through 13

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each arm

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	1.54 (6.54)	4.32 (7.85)
NovoLog	-1.83 (7.62)	1.34 (5.35)

14. Secondary Outcome

Title	Insulin Use - Automatic Basal Insulin
Description	Average amount per day (units) calculated for each participant under each therapy
Time Frame	Weeks 1 through 6, Weeks 8 through 13

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each arm

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	.87 (.307)	1.20 (.65)
NovoLog	.86 (.32)	1.20 (.66)

15. Secondary Outcome

Title	Insulin Pump - Active Insulin Time
Description	Average time per day (hours) calculated for each participant under each therapy
Time Frame	Weeks 1 through 6, Weeks 8 through 13

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each arm

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	3 (.06)	3 (0)
NovoLog	3 (0)	3 (.02)

16. Secondary Outcome

Title	Insulin Pump - Auto Mode
Description	Percentage of time spent in auto-mode after calibration under each therapy
Time Frame	Weeks 3 through 6, Weeks 10 through 13

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each arm

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	89.28 (6.42)	89.31 (8.42)
NovoLog	86.17 (11.43)	87.2 (15.6)

17. Secondary Outcome

Title	Insulin Pump - Manual Mode
Description	Percentage of time spent in manual-mode after calibration under each therapy
Time Frame	Weeks 3 through 6, Weeks 10 through 13

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each arm

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	10.72 (6.42)	10.69 (8.42)
NovoLog	13.45 (11.44)	12.8 (15.6)

18. Secondary Outcome

Title	Change in Carbohydrate Ratio
Description	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
Time Frame	Weeks 1 through 6, Weeks 8 through 13

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each arm

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	-.27 (1.09)	-.02 (.47)
NovoLog	-.14 (.95)	.2 (.76)

19. Secondary Outcome

Title	Infusion Site Reactions
Description	Number of Infusion site reactions reported by patient
Time Frame	14 week treatment period

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each arm

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	0	1
NovoLog	3	2

20. Secondary Outcome

Title	Pump Occlusions
Description	Number of Occlusion events reported by patient
Time Frame	14 week treatment period

Outcome Measure Data

Analysis Population Description

All patients who participated in the meal test after 6 weeks of therapy in each arm

Arm/Group Title	Fiasp/Novolog	Novolog/Fiasp
Arm/Group Description	Participants with type 1 diabetes spent 6 weeks on Fiasp® then crossed over to 6 weeks on Novolog®	Participants with type 1 diabetes spent 6 weeks on Novolog® then crossed over to 6 weeks on Fiasp®
Measure Participants	20	17
Fiasp	7	6
NovoLog	7	9

Adverse Events

Time Frame	Approximately 20 weeks. The entire duration of the subjects study period.
Adverse Event Reporting Description	Adverse event information was collected at all phone or office visits during the trial.
Arm/Group Title	Fiasp/Novolog		Novolog/Fiasp
Arm/Group Description	7 weeks on Fiasp® then crossover to 7 weeks on Novolog® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion Fiasp®: Fiasp® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system Novolog®: Novolog® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system 670G hybrid closed loop continuous subcutaneous insulin infusion system: CSII		7 weeks on Novolog® then crossover to 7 weeks on Fiasp® in subjects on the 670g Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion Fiasp®: Fiasp® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system Novolog®: Novolog® used in a 670G hybrid closed loop continuous subcutaneous insulin infusion system 670G hybrid closed loop continuous subcutaneous insulin infusion system: CSII
All Cause Mortality
	Fiasp/Novolog		Novolog/Fiasp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/18 (0%)
Serious Adverse Events
	Fiasp/Novolog		Novolog/Fiasp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/19 (5.3%)		0/18 (0%)
Musculoskeletal and connective tissue disorders
Herniated Disc	1/19 (5.3%)	1	0/18 (0%)	0
Other (Not Including Serious) Adverse Events
	Fiasp/Novolog		Novolog/Fiasp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/19 (57.9%)		7/18 (38.9%)
Cardiac disorders
Trivial tricuspid regurgitation	0/19 (0%)	0	1/18 (5.6%)	18
Trivial mitral regurgitation	0/19 (0%)	0	1/18 (5.6%)	1
First Degree AV Block	0/19 (0%)	0	1/18 (5.6%)	1
Intermittent Heart Palpitations	0/19 (0%)	0	1/18 (5.6%)	1
Intermittent bradycardia	1/19 (5.3%)	1	0/18 (0%)	0
Worsening of Hypertension	1/19 (5.3%)	1	0/18 (0%)	0
Supraventricular Tachycardia	1/19 (5.3%)	1	0/18 (0%)	0
Hyperkalemia	1/19 (5.3%)	1	0/18 (0%)	0
Endocrine disorders
Worsening of hypocalcemia	0/19 (0%)	0	1/18 (5.6%)	1
Worsening of hypothyroidsm	1/19 (5.3%)	1	0/18 (0%)	0
Eye disorders
Non Proliferative Diabetic Retinopathy	0/19 (0%)	0	1/18 (5.6%)	1
Center involved diabetic macular edema (right eye)	1/19 (5.3%)	1	0/18 (0%)	0
Gastrointestinal disorders
Gasteroenteritis	1/19 (5.3%)	1	1/18 (5.6%)	1
Traveler's Diarrhea	1/19 (5.3%)	1	0/18 (0%)	0
Hiatial Hernia	1/19 (5.3%)	1	0/18 (0%)	0
Gastroesophageal reflux disease	1/19 (5.3%)	1	0/18 (0%)	0
Nausea	1/19 (5.3%)	1	0/18 (0%)	0
General disorders
Worsening of Seasonal Allergic Rhinitis	0/19 (0%)	0	1/18 (5.6%)	1
Sore Throat	0/19 (0%)	0	1/18 (5.6%)	1
Nasal Congestion	0/19 (0%)	0	1/18 (5.6%)	1
Fever	0/19 (0%)	0	1/18 (5.6%)	1
Abdominal Cramps	1/19 (5.3%)	1	0/18 (0%)	0
Emesis	1/19 (5.3%)	1	0/18 (0%)	0
Ecchymosis (bilateral hands)	1/19 (5.3%)	1	0/18 (0%)	0
Vasovagal Syncope	1/19 (5.3%)	1	0/18 (0%)	0
Infections and infestations
Influenza	0/19 (0%)	0	1/18 (5.6%)	1
Viral infection	0/19 (0%)	0	1/18 (5.6%)	1
Conjuntivitis	0/19 (0%)	0	1/18 (5.6%)	1
Common Cold	2/19 (10.5%)	3	1/18 (5.6%)	1
Sinus Infection	0/19 (0%)	0	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
Headache	0/19 (0%)	0	1/18 (5.6%)	1
Herniated Disc	1/19 (5.3%)	1	0/18 (0%)	0
Back pain	1/19 (5.3%)	1	0/18 (0%)	0
Right index finger dislocation	0/19 (0%)	0	1/18 (5.6%)	1
Triangular fibrocartilage band tear (left wrist)	0/19 (0%)	0	1/18 (5.6%)	1
myalgia (bilateral shoulders0	1/19 (5.3%)	1	0/18 (0%)	0
Product Issues
Irritation at Infusion site (abdoment)	0/19 (0%)	0	1/18 (5.6%)	1
Renal and urinary disorders
acute kidney injury	1/19 (5.3%)	1	0/18 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/19 (0%)	0	1/18 (5.6%)	1
Bronchitis	1/19 (5.3%)	1	1/18 (5.6%)	1
Skin and subcutaneous tissue disorders
Redness at infusion site (right abdomen)	1/19 (5.3%)	1	0/18 (0%)	0
Right Thumb laceration	1/19 (5.3%)	1	0/18 (0%)	0
erythema at infusion site	1/19 (5.3%)	1	1/18 (5.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.