Efficacy and Safety of Faster-acting Insulin Aspart Compared to NovoRapid® Both in Combination With Insulin Degludec in Adults With Type 1 Diabetes (onset®8)

This trial is conducted in Asia, Europe and North America. The purpose is to confirm efficacy in terms of glycaemic control of treatment with mealtime faster-acting insulin aspart in combination with insulin degludec in adults with Type 1 Diabetes Mellitus.

Study Overview

• Status: Completed
• Conditions: Diabetes; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Faster-acting insulin aspart; Drug: insulin degludec; Drug: insulin aspart

• Study Type: Interventional
• Enrollment (Actual): 1108
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Novo Nordisk Investigational Site
  • Salzburg, Austria, 5020
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1130
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1030
    • Novo Nordisk Investigational Site
• Bulgaria
  • Dimitrovgrad, Bulgaria, 6400
    • Novo Nordisk Investigational Site
  • Pleven, Bulgaria, 5800
    • Novo Nordisk Investigational Site
  • Plovdiv, Bulgaria, 4002
    • Novo Nordisk Investigational Site
  • Ruse, Bulgaria, 7000
    • Novo Nordisk Investigational Site
  • Sofia, Bulgaria, 1431
    • Novo Nordisk Investigational Site
  • Sofia, Bulgaria, 1606
    • Novo Nordisk Investigational Site
  • Varna, Bulgaria, 9010
    • Novo Nordisk Investigational Site
• Canada
  • Quebec, Canada, G1V 4G2
    • Novo Nordisk Investigational Site
  • Quebec, Canada, G1V 4G5
    • Novo Nordisk Investigational Site
  • Alberta
    • Calgary, Alberta, Canada, T2H 2G4
      • Novo Nordisk Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Novo Nordisk Investigational Site
  • Ontario
    • Concord, Ontario, Canada, L4K 4M2
      • Novo Nordisk Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H2W 1R7
      • Novo Nordisk Investigational Site
• Germany
  • Berlin, Germany, 12163
    • Novo Nordisk Investigational Site
  • Berlin, Germany, 13597
    • Novo Nordisk Investigational Site
  • Dresden, Germany, 01219
    • Novo Nordisk Investigational Site
  • Falkensee, Germany, 14612
    • Novo Nordisk Investigational Site
  • Lingen, Germany, 49808
    • Novo Nordisk Investigational Site
  • Münster, Germany, 48145
    • Novo Nordisk Investigational Site
  • Neuwied, Germany, 56564
    • Novo Nordisk Investigational Site
  • Schweinfurt, Germany, 97421
    • Novo Nordisk Investigational Site
• India
  • Chandigarh, India, 160012
    • Novo Nordisk Investigational Site
  • New Dehli, India, 110029
    • Novo Nordisk Investigational Site
  • New Delhi, India, 110001
    • Novo Nordisk Investigational Site
  • Pune, India, 411011
    • Novo Nordisk Investigational Site
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500072
      • Novo Nordisk Investigational Site
    • Visakhapatnam, Andhra Pradesh, India, 530002
      • Novo Nordisk Investigational Site
  • Gujarat
    • Ahmedabad, Gujarat, India, 380006
      • Novo Nordisk Investigational Site
    • Ahmedabad, Gujarat, India, 380052
      • Novo Nordisk Investigational Site
  • Haryana
    • Rohtak, Haryana, India, 124001
      • Novo Nordisk Investigational Site
  • Kerala
    • Kozhikode, Kerala, India, 673017
      • Novo Nordisk Investigational Site
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India, 452010
      • Novo Nordisk Investigational Site
    • Indore, Madhya Pradesh, India, 452008
      • Novo Nordisk Investigational Site
  • Maharashtra
    • Pune, Maharashtra, India, 411001
      • Novo Nordisk Investigational Site
  • Orissa
    • Bhubaneswar, Orissa, India, 751019
      • Novo Nordisk Investigational Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600086
      • Novo Nordisk Investigational Site
    • Chennai, Tamil Nadu, India, 600 013
      • Novo Nordisk Investigational Site
    • Vellore, Tamil Nadu, India, 632004
      • Novo Nordisk Investigational Site
• Israel
  • Haifa, Israel, 31096
    • Novo Nordisk Investigational Site
  • Holon, Israel, 58100
    • Novo Nordisk Investigational Site
  • Jerusalem, Israel, 91120
    • Novo Nordisk Investigational Site
  • Jerusalem, Israel, 93106
    • Novo Nordisk Investigational Site
  • Petah Tikva, Israel, 49202
    • Novo Nordisk Investigational Site
  • Rishon Le Zion, Israel, 75650
    • Novo Nordisk Investigational Site
• Italy
  • Ancona, Italy, 60100
    • Novo Nordisk Investigational Site
  • Bergamo, Italy, 24127
    • Novo Nordisk Investigational Site
  • Catanzaro, Italy, 88100
    • Novo Nordisk Investigational Site
  • Milano, Italy, 20132
    • Novo Nordisk Investigational Site
  • Rome, Italy, 00168
    • Novo Nordisk Investigational Site
  • Sesto San Giovanni (MI), Italy, 20099
    • Novo Nordisk Investigational Site
• Japan
  • Amagasaki-shi, Hyogo, Japan, 661-0002
    • Novo Nordisk Investigational Site
  • Chuo-ku, Tokyo, Japan, 103-0002
    • Novo Nordisk Investigational Site
  • Ebina-shi, Kanagawa, Japan, 243-0432
    • Novo Nordisk Investigational Site
  • Fukuoka, Japan, 830 8522
    • Novo Nordisk Investigational Site
  • Fukushima, Japan, 963-8851
    • Novo Nordisk Investigational Site
  • Hokkaido, Japan, 060-0062
    • Novo Nordisk Investigational Site
  • Hokkaido, Japan, 062-0007
    • Novo Nordisk Investigational Site
  • Ibaraki, Japan, 311-0113
    • Novo Nordisk Investigational Site
  • Ibaraki, Japan, 305-0812
    • Novo Nordisk Investigational Site
  • Izumisano-shi, Japan, 598 0048
    • Novo Nordisk Investigational Site
  • Kanagawa, Japan, 235-0045
    • Novo Nordisk Investigational Site
  • Kobe-shi, Hyogo, Japan, 657-0846
    • Novo Nordisk Investigational Site
  • Kumamoto, Japan, 862-0976
    • Novo Nordisk Investigational Site
  • Matsumoto-shi, Nagano, Japan, 390-8621
    • Novo Nordisk Investigational Site
  • Mito-shi, Ibaraki, Japan, 311-4153
    • Novo Nordisk Investigational Site
  • Miyazaki, Japan, 880-0034
    • Novo Nordisk Investigational Site
  • Oita-shi, Japan, 870 0039
    • Novo Nordisk Investigational Site
  • Osaka, Japan, 569-1045
    • Novo Nordisk Investigational Site
  • Osaka-shi, Osaka, Japan, 545 8586
    • Novo Nordisk Investigational Site
  • Ota-ku, Tokyo, Japan, 1430015
    • Novo Nordisk Investigational Site
  • Sapporo-shi, Hokkaido, Japan, 060-0001
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 105-8471
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 113-8431
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 162 8666
    • Novo Nordisk Investigational Site
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Novo Nordisk Investigational Site
• Russian Federation
  • Barnaul, Russian Federation, 656045
    • Novo Nordisk Investigational Site
  • Kazan, Russian Federation, 420061
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 119435
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 123423
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 125367
    • Novo Nordisk Investigational Site
  • Novosibirsk, Russian Federation, 630117
    • Novo Nordisk Investigational Site
  • Novosibirsk, Russian Federation, 630047
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 194358
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 195213
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 199226
    • Novo Nordisk Investigational Site
  • Saratov, Russian Federation, 410053
    • Novo Nordisk Investigational Site
  • Tumen, Russian Federation, 625023
    • Novo Nordisk Investigational Site
• Serbia
  • Belgrade, Serbia, 11000
    • Novo Nordisk Investigational Site
• Taiwan
  • Taipei, Taiwan, 112
    • Novo Nordisk Investigational Site
  • Taipei, Taiwan, 104
    • Novo Nordisk Investigational Site
  • Taoyuan, Taiwan, 333
    • Novo Nordisk Investigational Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85714
      • Novo Nordisk Investigational Site
  • California
    • Concord, California, United States, 94520
      • Novo Nordisk Investigational Site
    • Encino, California, United States, 91436
      • Novo Nordisk Investigational Site
    • Escondido, California, United States, 92025
      • Novo Nordisk Investigational Site
    • Fresno, California, United States, 93720
      • Novo Nordisk Investigational Site
    • Fullerton, California, United States, 92835
      • Novo Nordisk Investigational Site
    • Huntington Beach, California, United States, 92648
      • Novo Nordisk Investigational Site
    • Monterey, California, United States, 93940
      • Novo Nordisk Investigational Site
    • Newport Beach, California, United States, 92663
      • Novo Nordisk Investigational Site
    • Santa Barbara, California, United States, 93105
      • Novo Nordisk Investigational Site
    • Walnut Creek, California, United States, 94598
      • Novo Nordisk Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80209
      • Novo Nordisk Investigational Site
    • Golden, Colorado, United States, 80401
      • Novo Nordisk Investigational Site
  • Florida
    • Palm Harbor, Florida, United States, 34684
      • Novo Nordisk Investigational Site
    • Tampa, Florida, United States, 33607
      • Novo Nordisk Investigational Site
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Novo Nordisk Investigational Site
  • Idaho
    • Idaho Falls, Idaho, United States, 83404-7596
      • Novo Nordisk Investigational Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Novo Nordisk Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Novo Nordisk Investigational Site
    • Louisville, Kentucky, United States, 40213
      • Novo Nordisk Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Novo Nordisk Investigational Site
    • Rockville, Maryland, United States, 20852
      • Novo Nordisk Investigational Site
  • Michigan
    • Flint, Michigan, United States, 48503-5904
      • Novo Nordisk Investigational Site
    • Kalamazoo, Michigan, United States, 49048
      • Novo Nordisk Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • Novo Nordisk Investigational Site
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Novo Nordisk Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Novo Nordisk Investigational Site
  • New Hampshire
    • Nashua, New Hampshire, United States, 03063
      • Novo Nordisk Investigational Site
  • New Jersey
    • Hamilton, New Jersey, United States, 08690
      • Novo Nordisk Investigational Site
    • Lawrenceville, New Jersey, United States, 08648
      • Novo Nordisk Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109-2134
      • Novo Nordisk Investigational Site
  • New York
    • Albany, New York, United States, 12206
      • Novo Nordisk Investigational Site
    • Rochester, New York, United States, 14607
      • Novo Nordisk Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • Novo Nordisk Investigational Site
    • Greenville, North Carolina, United States, 27834
      • Novo Nordisk Investigational Site
    • Wilmington, North Carolina, United States, 28401
      • Novo Nordisk Investigational Site
  • Oregon
    • Bend, Oregon, United States, 97702
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Novo Nordisk Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • Novo Nordisk Investigational Site
  • Texas
    • Amarillo, Texas, United States, 79106
      • Novo Nordisk Investigational Site
    • Austin, Texas, United States, 78731
      • Novo Nordisk Investigational Site
    • Austin, Texas, United States, 78749
      • Novo Nordisk Investigational Site
    • Beaumont, Texas, United States, 77701
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75231
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75246
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75218
      • Novo Nordisk Investigational Site
    • Mesquite, Texas, United States, 75149
      • Novo Nordisk Investigational Site
    • Round Rock, Texas, United States, 78681
      • Novo Nordisk Investigational Site
  • Utah
    • Murray, Utah, United States, 84123
      • Novo Nordisk Investigational Site
    • Ogden, Utah, United States, 84405
      • Novo Nordisk Investigational Site
    • Salt Lake City, Utah, United States, 84102
      • Novo Nordisk Investigational Site
    • Salt Lake City, Utah, United States, 84107
      • Novo Nordisk Investigational Site
  • Washington
    • Federal Way, Washington, United States, 98003
      • Novo Nordisk Investigational Site
    • Renton, Washington, United States, 98057
      • Novo Nordisk Investigational Site
    • Spokane, Washington, United States, 99201
      • Novo Nordisk Investigational Site
    • Tacoma, Washington, United States, 98405
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria: - Male or female, age greater than or equal to 18 years ( for Japan and Taiwan: age greater than or equal to 20 years) at the time of signing informed consent - Type 1 Diabetes Mellitus (based on clinical judgement and/or supported by laboratory analysis as per local guidelines) 12 months or more prior to screening - Currently treated with a basal-bolus insulin regimen for at least 12 months prior to screening (Visit 1) - Currently treated with a basal insulin analogue for at least 4 months prior to screening (Visit 1) - HbA1c 7.0-9.5% (53-80 mmol/mol) (both inclusive) as assessed by central laboratory - Body Mass Index less than or equal to 35.0 kg/m^2 Exclusion Criteria: - Within the past 180 days any of the following: myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischemic attack - Subjects presently classified as being in New York Heart Association (NYHA) Class IV Currently planned coronary, carotid or peripheral artery revascularisation - Diabetic ketoacidosis requiring hospitalisation within the last 180 days prior to screening (Visit 1) - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of three months before screening (Visit 1)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mealtime faster-acting insulin aspart and insulin degludec	Drug: Faster-acting insulin aspart; Injected subcutaneously (under the skin) three times daily for 26 weeks. Dose individually adjusted. Mealtime dosing is defined as injecting 0-2 minutes before the meal. Postmeal dosing is defined as injecting 20 minutes after the start of the meal.; Drug: insulin degludec; Injected subcutaneously (under the skin) once daily for 26 weeks. Dose individually adjusted
Active Comparator: Mealtime NovoRapid® and insulin degludec	Drug: insulin degludec; Injected subcutaneously (under the skin) once daily for 26 weeks. Dose individually adjusted; Drug: insulin aspart; Injected subcutaneously (under the skin) three times daily for 26 weeks. Dose individually adjusted. Mealtime dosing is defined as injecting 0-2 minutes before the meal.
Experimental: Postmeal faster-acting insulin aspart and insulin degludec	Drug: Faster-acting insulin aspart; Injected subcutaneously (under the skin) three times daily for 26 weeks. Dose individually adjusted. Mealtime dosing is defined as injecting 0-2 minutes before the meal. Postmeal dosing is defined as injecting 20 minutes after the start of the meal.; Drug: insulin degludec; Injected subcutaneously (under the skin) once daily for 26 weeks. Dose individually adjusted

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c 26 Weeks After Randomisation	Change from baseline (week 0) in HbA1c was evaluated after 26 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In-trial period: the observation period from date of randomisation until last trial-related subject-site contact.	Week 0, week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 1-hour Post Prandial Glucose (PPG) Increment 26 Weeks After Randomisation (Meal Test)	The 1-hour PPG increment was analysed based on the laboratory-measured values in the meal test, and was derived using the 1-hour PPG measurement minus the pre-prandial plasma glucose (PG). The results are based on the last in-trial value, which included the last available measurement in the in-trial period.	Week 0, week 26
Change From Baseline in 1,5-anhydroglucitol 26 Weeks After Randomisation	The results are based on the last in-trial value, which included the last available measurement in the in-trial period.	Week 0, week 26
Change From Baseline in Fasting Plasma Glucose (FPG) 26 Weeks After Randomisation	The results are based on the last in-trial value, which included the last available measurement in the in-trial period.	Week 0, week 26
Percentage of Subjects Reaching HbA1c Targets (HbA1c < 7.0%) 26 Weeks After Randomisation	The percentage of subjects who achieved the HbA1c target of <7.0% 26 weeks after randomisation. Subjects without an HbA1c measurement at week 26 were treated as non-responders.	26 weeks after randomisation
Percentage of Subjects Reaching HbA1c Targets (HbA1c < 7.0% Without Severe Hypoglycaemia) 26 Weeks After Randomisation	The percentage of subjects who achieved the HbA1c target of <7.0% without severe hypoglycaemia 26 weeks after randomisation. Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. Subjects without an HbA1c measurement at week 26 were treated as non-responders.	26 weeks after randomisation
Percentage of Subjects Reaching HbA1c Targets (HbA1c < 7.0% Without Severe Hypoglycaemia and Minimal Weight Gain [<3.0%]) 26 Weeks After Randomisation	The percentage of subjects who achieved the HbA1c target of <7.0% without severe hypoglycaemia and with minimal weight gain (defined as less than a 3% increase) 26 weeks after randomisation. Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. Subjects without an HbA1c measurement at week 26 or without body weight measurement at week 26 were treated as non-responders.	26 weeks after randomisation
Change From Baseline in 30- Min, 1- Hour, 2- Hour, 3- Hour and 4- Hour PPG 26 Weeks After Randomisation	Laboratory measured PG from the meal test was analysed for 30, 60, 120, 180, and 240 minutes PPG separately. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.	Week 0, week 26
Change From Baseline in 30- Min, 1- Hour, 2- Hour, 3- Hour and 4- Hour PPG Increment 26 Weeks After Randomisation	Laboratory measured PG from the meal test was analysed for 30, 60, 120, 180, and 240 minutes PPG separately. The corresponding PPG increments were derived separately using each PPG measurement minus the pre-prandial PG. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.	Week 0, week 26
Change From Baseline in 7-9-7-point Self-measured Plasma Glucose (SMPG) 26 Weeks After Randomisation: Mean of the 7-9-7-point Profile	The subject was instructed to perform a 7-9-7 SMPG point profile on the 3 consecutive days just before selected visit. 7-point profile (day 3 and day 1 before selected visit): before breakfast, 60 minutes after the start of breakfast, before lunch, 60 minutes after the start of lunch, before main evening meal, 60 minutes after the start of main evening meal, and at bedtime. 9-point profile (day 2 before selected visit) included all timepoints of 7-points profile with addition of SMPG measurement at 4 a.m. and before breakfast on the following day. The mean of the 7-9-7-point profile was defined as the area under the curve profile divided by the measurement time, and was calculated using the linear trapezoidal technique. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.	Week 0, week 26
Change From Baseline in 7-9-7-point SMPG 26 Weeks After Randomisation: PPG (Mean, Breakfast, Lunch, Main Evening Meal)	The subject was instructed to perform a 7-9-7 SMPG point profile on the 3 consecutive days just before selected visit. 7-point profile (day 3 and day 1 before selected visit): before breakfast, 60 minutes after the start of breakfast, before lunch, 60 minutes after the start of lunch, before main evening meal, 60 minutes after the start of main evening meal, and at bedtime. 9-point profile (day 2 before selected visit) included all timepoints of 7-points profile with addition of SMPG measurement at 4 a.m. and before breakfast on the following day. Results were derived from the three profiles: post-breakfast, post-lunch, post-main evening meal. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.	Week 0, week 26
Change From Baseline in 7-9-7-point SMPG 26 Weeks After Randomisation: PPG Increment (Mean, Breakfast, Lunch, Main Evening Meal)	The subject was instructed to perform a 7-9-7 SMPG point profile on the 3 consecutive days just before selected visit. 7-point profile (day 3 and day 1 before selected visit): before breakfast, 60 minutes after the start of breakfast, before lunch, 60 minutes after the start of lunch, before main evening meal, 60 minutes after the start of main evening meal, and at bedtime. 9-point profile (day 2 before selected visit) included all timepoints of 7-points profile with addition of SMPG measurement at 4 a.m. and before breakfast on the following day. PPG increment for each meal (breakfast, lunch, main evening meal) was derived from the 7-point and 9-point profile as the difference between PPG values and the PG value before the meal in each separate profile. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.	Week 0, week 26
Change From Baseline in 7-9-7-point SMPG 26 Weeks After Randomisation: Fluctuation in 7-9-7-point Profile	The subject was instructed to perform a 7-9-7 SMPG point profile on the 3 consecutive days just before selected visit. 7-point profile (day 3 and day 1 before selected visit): before breakfast, 60 minutes after the start of breakfast, before lunch, 60 minutes after the start of lunch, before main evening meal, 60 minutes after the start of main evening meal, and at bedtime. 9-point profile (day 2 before selected visit) included all timepoints of 7-points profile with addition of SMPG measurement at 4 a.m. and before breakfast on the following day. Fluctuation in SMPG profile was the average absolute difference from the mean of the SMPG profile. Change from baseline is represented as ratio to baseline value. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.	Week 0, week 26
Change From Baseline in 7-9-7-point SMPG 26 Weeks After Randomisation: Change in the Nocturnal Self-measured Plasma Glucose Measurements	The subject was instructed to perform 7-9-7 SMPG point profile on 3 consecutive days just before selected visit. 7-point profile (day 3 and day 1 before selected visit): before breakfast,60 minutes after the start of breakfast,before lunch,60 minutes after the start of lunch, before main evening meal,60 minutes after the start of main evening meal,and at bedtime. 9-point profile (day 2 before selected visit) included all timepoints of 7-points profile with addition of SMPG measurement at 4 a.m. and before breakfast on following day. Change from baseline in nocturnal PG values (nocturnal increments) was assessed by considering differences between PG values available at bedtime, at 4 a.m and the before breakfast value the following day: (04:00 PG value minus at bedtime PG value), (before breakfast PG value minus at bedtime PG value) and (before breakfast PG value minus 04:00 PG value). Results are based on the last in-trial value (the last available measurement in the in-trial period).	Week 0, week 26
Percentage of Subjects Reaching PPG Target (Overall Mean of Daily PPG Measurements in SMPG) 26 Weeks After Randomisation: Overall PPG (1 Hour) ≤7.8 mmol/L	Percentage of subjects achieving an overall mean 1-hour PPG ≤7.8 mmol/L [140 mg/dL] 26 weeks after randomisation. Subjects without an overall mean 1-hour PPG at week 26 were treated as non-responders.	26 weeks after randomisation
Percentage of Subjects Reaching PPG Target (Overall Mean of Daily PPG Measurements in SMPG) 26 Weeks After Randomisation: Overall PPG (1 Hour) ≤7.8 mmol/L Without Severe Hypoglycaemia	Percentage of subjects achieving an overall mean 1-hour PPG ≤7.8 mmol/L [140 mg/dL] 26 weeks after randomisation without severe hypoglycaemia. Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. Subjects without an overall mean 1-hour PPG at week 26 were treated as non-responders.	26 weeks after randomisation
Percentage of Subjects Reaching PPG Target (Overall Mean of Daily PPG Measurements in SMPG) 26 Weeks After Randomisation: Overall PPG (1 Hour) ≤7.8 mmol/L and HbA1c <7.0% and Minimal Weight Gain (<3.0%) Without Severe Hypoglycaemia	The percentage of subjects who achieved overall mean 1 hour PPG ≤7.8 mmol/L [140 mg/dL], had HbA1c < 7.0% and had minimal weight gain (increase in body weight from baseline <3.0%) 26 weeks after randomisation, and without severe hypoglycaemic episodes. Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. Subjects without an overall mean 1-hour PPG or an HbA1c value or a body weight at week 26 were treated as non-responders.	26 weeks after randomisation
Change From Baseline in Lipids-lipoproteins Profile 26 Weeks After Randomisation (Total Cholesterol, High Density Lipoproteins [HDL] Cholesterol, Low Density Lipoproteins [LDL] Cholesterol)	Change from baseline in HDL cholesterol, LDL cholesterol and total cholesterol 26 weeks after randomization are represented as ratio to baseline values. The results are based on the last in-trial value (the last available measurement in the in-trial period).	Week 0, week 26
Insulin Dose (Basal Insulin Dose, Total and Individual Meal Insulin Dose)	The insulin doses were summarised descriptively at week 0 and week 26 both by meal type and as total daily dose (total daily and separately for each mealtime dose). Week 26 results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.	Week 0, week 26
Number of Treatment Emergent Adverse Events During 26 Weeks After Randomisation	A treatment emergent adverse event (TEAE) was defined as an event that had an onset date on or after the first day of exposure to randomised treatment, and no later than seven days after the last day of randomised treatment.	Week 0 to week 26 (+7 days)
Number of Treatment-emergent Injection Site Reactions During the 26 Weeks After Randomisation	A treatment emergent event was defined as an event that had an onset date on or after the first day of exposure to randomised treatment, and no later than seven days after the last day of randomised treatment.	Week 0 to week 26 (+7 days)
Number of Hypoglycaemic Episodes Classified Both According to the American Diabetes Association (ADA) Definition and Novo Nordisk (NN) Definition During 26 Weeks After Randomisation: Overall	ADA classification includes following criteria: Severe,Documented symptomatic,Asymptomatic,Probable symptomatic,Pseudo-hypoglycaemia. NN Classification: Severe:same as per ADA classification; Symptomatic blood glucose (BG) confirmed: PG<3.1 mmol/L with symptoms consistent with hypoglycaemia; Asymptomatic BG confirmed:PG<3.1 mmol/L without symptoms consistent with hypoglycaemia; Severe or BG confirmed symptomatic:severe according to ADA classification or BG confirmed by PG<3.1 mmol/L with symptoms consistent with hypoglycaemia; BG confirmed:PG<3.1 mmol/L with or without symptoms consistent with hypoglycaemia; Severe or BG confirmed:severe according to ADA classification or BG confirmed by PG<3.1 mmol/L with or without symptoms consistent with hypoglycaemia; Unclassifiable Results represent total number of hypoglycaemic episodes. Treatment emergent episode: an event that has onset up to 1 day after last day of randomised treatment and excluding events occurring in run-in period.	Week 0 to week 26 (+1 day)
Number of Hypoglycaemic Episodes Classified Both According to the ADA Definition and Novo Nordisk Definition During 26 Weeks After Randomisation: Daytime and Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive)	ADA classification includes following criteria: Severe, Documented symptomatic, Asymptomatic, Probable symptomatic, Pseudo-hypoglycaemia. NN Classification: Severe: same as per ADA classification; Symptomatic BG confirmed: PG<3.1 mmol/L with symptoms consistent with hypoglycaemia; Asymptomatic BG confirmed: PG<3.1 mmol/L without symptoms consistent with hypoglycaemia; Severe or BG confirmed symptomatic: severe according to the ADA classification or BG confirmed by PG<3.1 mmol/Lwith symptoms consistent with hypoglycaemia; BG confirmed: PG<3.1 mmol/L with or without symptoms consistent with hypoglycaemia; Severe or BG confirmed: severe according to the ADA classification or BG confirmed by PG<3.1 mmol/L with or without symptoms consistent with hypoglycaemia; Unclassifiable Results represent total number of hypoglycaemic episodes. Nocturnal hypoglycaemic episodes were episodes occurring between 00:01 and 05:59 both inclusive.	Week 0 to week 26 (+1 day)
Number of Hypoglycaemic Episodes Classified Both According to the ADA Definition and Novo Nordisk Definition During 26 Weeks After Randomisation: From Start of Meal Until 1,2, 4 Hours and From 2 Hours (Exclusive) to 4 Hours (Inclusive) After Start of Meal	ADA classification includes following criteria: Severe, Documented symptomatic, Asymptomatic, Probable symptomatic, Pseudo-hypoglycaemia. NN Classification: Severe: same as per ADA classification; Symptomatic BG confirmed: PG<3.1 mmol/L with symptoms consistent with hypoglycaemia; Asymptomatic BG confirmed: PG<3.1 mmol/L without symptoms consistent with hypoglycaemia; Severe or BG confirmed symptomatic: severe according to the ADA classification or BG confirmed by PG<3.1 mmol/Lwith symptoms consistent with hypoglycaemia; BG confirmed: PG<3.1 mmol/L with or without symptoms consistent with hypoglycaemia; Severe or BG confirmed: severe according to the ADA classification or BG confirmed by PG<3.1 mmol/L with or without symptoms consistent with hypoglycaemia; Unclassifiable Results represent total number of hypoglycaemic episodes related to meals.	Week 0 to week 26 (+1 day)
Change From Baseline 26 Weeks After Randomisation in Clinical Evaluations (Physical Examination)	The physical examination parameters included head, ears, eyes, nose, throat, neck; respiratory system; cardiovascular system; gastrointestinal system including mouth; musculoskeletal system; central and peripheral nervous system; and skin. The examinations were measured as 'normal', 'abnormal, not clinically significant' (Abn, NCS) or 'abnormal, clinically significant' (Abn, CS). Reported results are percentage of subjects with 'normal', 'Abn, NCS' and 'Abn, CS' physical examinations at week 0 and week 26. Week 26 results are based on the last on-treatment value (last value), which included the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Blood Pressure 26 Weeks After Randomisation	Change from baseline in systolic blood pressure and diastolic blood pressure 26 weeks after randomisation. Results are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Pulse 26 Weeks After Randomisation	Results are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Clinical Evaluation (Electrocardiogram) 26 Weeks After Randomisation	The electrocardiogram was interpreted by the investigator into following categories: Normal; Abn, NCS; Abnormal, CS. Reported results are percentage of subjects with 'normal', 'Abn, NCS' and 'Abn, CS' physical examinations at week 0 and week 26. Week 26 data are based on the last on-treatment value which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Clinical Evaluation (Fundoscopy/Fundus Photography) 26 Weeks After Randomisation	The result of the fundus photography/dilated fundoscopy was interpreted by the investigator into following categories: Normal; Abn, NCS; Abnormal, CS. Reported results are percentage of subjects with 'normal', 'Abn, NCS' and 'Abn, CS' fundoscopy/fundus photography results at week 0 and week 26. Week 26 data are based on the last on-treatment value which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Erythrocytes 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Haematocrit 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Haemoglobin 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Leukocytes 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Thrombocytes 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Alanine Aminotransferase 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Albumin 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Alkaline Phosphatase 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Aspartate Aminotransferase 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Total Bilirubin 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Potassium 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Creatinine 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Total Protein 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Urinary Albumin-to-creatinine Ratio 26 Weeks After Randomisation	Week 26 data are based on the last on-treatment value, which contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Urinalysis (Ketones) 26 Weeks After Randomisation	Presence of ketone in urine was assessed by urine dipstick and categorised as: Negative, Positive, Trace, 1+, 2+, 3+. Change from baseline is represented in terms of percentage of patients with ketone values at week 0 and week 26 (last on-treatment value). Last on-treatment value contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Urinalysis (Protein) 26 Weeks After Randomisation	Presence of protein in urine was assessed by urine dipstick and categorised as: Negative, Positive, Trace, 1+, 2+, 3+. Change from baseline is represented in terms of percentage of patients with protein values at week 0 and week 26 (last on-treatment value). Last on-treatment value contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Urinalysis (Erythrocytes) 26 Weeks After Randomisation	Presence of erythrocytes in urine was assessed by urine dipstick and categorised as: Negative, Positive, Trace, 1+, 2+, 3+. Change from baseline is represented in terms of percentage of patients with erythrocytes values at week 0 and week 26 (last on-treatment value). Last on-treatment value contains the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Anti-insulin Aspart (Specific and Cross-reacting With Human Insulin) Antibody Development 26 Weeks After Randomisation	Insulin aspart antibody titres (antibodies specific for insulin aspart and those cross-reacting with human insulin) measured at baseline and at 26 weeks. Week 26 data are based on the last on-treatment value which contains the last available measurement in the on-treatment period. Anti-insulin aspart antibody was measured as % bound radioactivity-labelled insulin aspart/Total added radioactivity-labelled insulin aspart (%B/T).	Week 0, week 26
Change From Baseline in Body Weight 26 Weeks After Randomisation	The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.	Week 0, week 26
Change From Baseline in Body Mass Index 26 Weeks After Randomisation	The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.	Week 0, week 26

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Rose L, Kadowaki T, Pieber TR, Buchholtz K, Ekelund M, Gorst-Rasmussen A, Philis-Tsimikas A. Efficacy and Safety of Fast-Acting Insulin Aspart in People with Type 1 Diabetes Using Carbohydrate Counting: A Post Hoc Analysis of Two Randomised Controlled Trials. Diabetes Ther. 2019 Jun;10(3):1029-1041. doi: 10.1007/s13300-019-0608-4. Epub 2019 Apr 4.
• Buse JB, Carlson AL, Komatsu M, Mosenzon O, Rose L, Liang B, Buchholtz K, Horio H, Kadowaki T. Fast-acting insulin aspart versus insulin aspart in the setting of insulin degludec-treated type 1 diabetes: Efficacy and safety from a randomized double-blind trial. Diabetes Obes Metab. 2018 Dec;20(12):2885-2893. doi: 10.1111/dom.13545. Epub 2018 Oct 10.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2016
• Primary Completion (Actual): July 17, 2017
• Study Completion (Actual): August 16, 2017

Study Registration Dates

• First Submitted: July 15, 2015
• First Submitted That Met QC Criteria: July 15, 2015
• First Posted (Estimate): July 16, 2015

Study Record Updates

• Last Update Posted (Actual): June 12, 2019
• Last Update Submitted That Met QC Criteria: May 28, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination
• Other Study ID Numbers: NN1218-4131; 2015-001047-36 (EudraCT Number); U1111-1167-9495 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No