Efficacy and Safety of Faster-acting Insulin Aspart Compared to NovoRapid® Both in Combination With Insulin Degludec in Children and Adolescents With Type 1 Diabetes

Diabetes Clinical Trial

— onset®7  

Official title:

Efficacy and Safety of Faster-acting Insulin Aspart Compared to NovoRapid® Both in Combination With Insulin Degludec in Children and Adolescents With Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02670915
• Other study ID #: NN1218-4101
• Secondary ID: 2014-002568-33U1
• Status: Completed
• Phase: Phase 3
• Start date: May 4, 2016
• Est. completion date: March 3, 2018

Study information

• Verified date: May 2019
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted globally. The aim of the trial is to investigate efficacy and safety of faster-acting insulin aspart compared to NovoRapid® both in combination with insulin degludec in children and adolescents with type 1 diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 834
• Est. completion date: March 3, 2018
• Est. primary completion date: February 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

Inclusion Criteria: - Male or female, 1 year above or equal to age below 18 years at the time of signing informed consent and below 18 years at the time of randomisation - Diagnosed with type 1 diabetes mellitus (based on clinical judgement and supported by laboratory analysis as per local guidelines) - Ongoing daily treatment with a basal-bolus insulin regimen using basal insulin analogue or Neutral Protamine Hagedorn (NPH) insulin for at least 90 days prior to the screening visit - HbA1c (glycosylated haemoglobin) below or equal 9.5% (80 mmol/mol) analysed by the central laboratory at the screening visit Exclusion Criteria: - More than one episode of diabetic ketoacidosis requiring hospitalisation within the last 90 days prior to the screening visit - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before screening

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Drug:
• Faster-acting insulin aspart
For subcutaneous (s.c., under the skin) injection once daily.
• insulin aspart
For subcutaneous (s.c., under the skin) injection once daily.
• insulin degludec
For subcutaneous (s.c., under the skin) injection once daily.

Locations

Country	Name	City	State
Bulgaria	Novo Nordisk Investigational Site	Pleven
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Varna
Czechia	Novo Nordisk Investigational Site	Hradec Kralove
Czechia	Novo Nordisk Investigational Site	Opava
Czechia	Novo Nordisk Investigational Site	Ostrava - Poruba
Czechia	Novo Nordisk Investigational Site	Pardubice
Czechia	Novo Nordisk Investigational Site	Praha
Czechia	Novo Nordisk Investigational Site	Usti nad Labem
Estonia	Novo Nordisk Investigational Site	Tallinn
Estonia	Novo Nordisk Investigational Site	Tartu
Finland	Novo Nordisk Investigational Site	Espoo
Finland	Novo Nordisk Investigational Site	OYS
Finland	Novo Nordisk Investigational Site	Seinäjoki
Germany	Novo Nordisk Investigational Site	Bochum
Germany	Novo Nordisk Investigational Site	Freiburg
Germany	Novo Nordisk Investigational Site	Hannover
Germany	Novo Nordisk Investigational Site	Ludwigshafen
Germany	Novo Nordisk Investigational Site	Münster
Germany	Novo Nordisk Investigational Site	Neuwied
Germany	Novo Nordisk Investigational Site	Oldenburg
Germany	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach
India	Novo Nordisk Investigational Site	Ahmedabad	Gujarat
India	Novo Nordisk Investigational Site	Chennai	Tamil Nadu
India	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh
India	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh
India	Novo Nordisk Investigational Site	Indore	Madhya Pradesh
India	Novo Nordisk Investigational Site	Kochi	Kerala
India	Novo Nordisk Investigational Site	Kolkata
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	New Delhi
India	Novo Nordisk Investigational Site	Pune	Maharashtra
Israel	Novo Nordisk Investigational Site	Beer Sheva
Israel	Novo Nordisk Investigational Site	Haifa
Israel	Novo Nordisk Investigational Site	Holon
Israel	Novo Nordisk Investigational Site	Petah Tikva
Israel	Novo Nordisk Investigational Site	Tel Aviv
Israel	Novo Nordisk Investigational Site	Zerifin
Italy	Novo Nordisk Investigational Site	Ancona
Italy	Novo Nordisk Investigational Site	Catanzaro
Italy	Novo Nordisk Investigational Site	Chieti
Italy	Novo Nordisk Investigational Site	Napoli
Italy	Novo Nordisk Investigational Site	Verona
Japan	Novo Nordisk Investigational Site	Amagasaki-shi, Hyogo
Japan	Novo Nordisk Investigational Site	Chuo-shi, Yamanashi
Japan	Novo Nordisk Investigational Site	Fukuoka
Japan	Novo Nordisk Investigational Site	Hiroshima-shi, Hiroshima
Japan	Novo Nordisk Investigational Site	Iruma-gun, Saitama
Japan	Novo Nordisk Investigational Site	Kitakyushu,Fukuoka
Japan	Novo Nordisk Investigational Site	Kitakyushu-shi, Fukuoka
Japan	Novo Nordisk Investigational Site	Kobe-shi, Hyogo
Japan	Novo Nordisk Investigational Site	Kobe-shi, Hyogo
Japan	Novo Nordisk Investigational Site	Kochi-shi, Kochi
Japan	Novo Nordisk Investigational Site	Kofu, Yamanashi
Japan	Novo Nordisk Investigational Site	Kumamoto-shi, Kumamoto
Japan	Novo Nordisk Investigational Site	Kure-shi, Hiroshima
Japan	Novo Nordisk Investigational Site	Kyoto
Japan	Novo Nordisk Investigational Site	Maebashi-shi, Gunma
Japan	Novo Nordisk Investigational Site	Matsumoto-shi, Nagano,
Japan	Novo Nordisk Investigational Site	Matsuyama-shi, Ehime
Japan	Novo Nordisk Investigational Site	Musashino-shi, Tokyo
Japan	Novo Nordisk Investigational Site	Niigata-shi, Niigata
Japan	Novo Nordisk Investigational Site	Niigata-shi, Niigata
Japan	Novo Nordisk Investigational Site	Okayama Kita-ku, Okayama
Japan	Novo Nordisk Investigational Site	Okayama-shi, Okayama
Japan	Novo Nordisk Investigational Site	Okayama-shi, Okayama
Japan	Novo Nordisk Investigational Site	Osaka-shi, Osaka
Japan	Novo Nordisk Investigational Site	Ota-shi, Gunma
Japan	Novo Nordisk Investigational Site	Otsu-shi, Shiga
Japan	Novo Nordisk Investigational Site	Saga-shi, Saga
Japan	Novo Nordisk Investigational Site	Sendai-shi, Miyagi
Japan	Novo Nordisk Investigational Site	Suzaka-shi ,Nagano
Japan	Novo Nordisk Investigational Site	Tochigi
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tsu-shi, Mie
Japan	Novo Nordisk Investigational Site	Yokohama-shi, Kanagawa
Japan	Novo Nordisk Investigational Site	Yokosuka-shi, Kanagawa
Latvia	Novo Nordisk Investigational Site	Riga
Lithuania	Novo Nordisk Investigational Site	Kaunas
Poland	Novo Nordisk Investigational Site	Gdansk
Poland	Novo Nordisk Investigational Site	Warszawa
Poland	Novo Nordisk Investigational Site	Warszawa
Poland	Novo Nordisk Investigational Site	Wroclaw
Puerto Rico	Novo Nordisk Investigational Site	San Juan
Russian Federation	Novo Nordisk Investigational Site	Kazan
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Novosibirsk
Russian Federation	Novo Nordisk Investigational Site	Rostov-on-Don
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Samara
Russian Federation	Novo Nordisk Investigational Site	Saratov
Russian Federation	Novo Nordisk Investigational Site	Tomsk
Russian Federation	Novo Nordisk Investigational Site	Ufa
Serbia	Novo Nordisk Investigational Site	Belgrade
Serbia	Novo Nordisk Investigational Site	Belgrade
Serbia	Novo Nordisk Investigational Site	Nis
Serbia	Novo Nordisk Investigational Site	Novi Sad
Turkey	Novo Nordisk Investigational Site	Adana
Turkey	Novo Nordisk Investigational Site	Antalya
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Izmir
Turkey	Novo Nordisk Investigational Site	Izmir
Turkey	Novo Nordisk Investigational Site	Samsun
Ukraine	Novo Nordisk Investigational Site	Dnipro
Ukraine	Novo Nordisk Investigational Site	Ivano-Frankivsk
Ukraine	Novo Nordisk Investigational Site	Kharkiv
Ukraine	Novo Nordisk Investigational Site	Kharkiv
Ukraine	Novo Nordisk Investigational Site	Kiev
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Lviv
Ukraine	Novo Nordisk Investigational Site	Vinnytsia
Ukraine	Novo Nordisk Investigational Site	Zaporizhzhia
United States	Novo Nordisk Investigational Site	Amarillo	Texas
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Aurora	Colorado
United States	Novo Nordisk Investigational Site	Austin	Texas
United States	Novo Nordisk Investigational Site	Baltimore	Maryland
United States	Novo Nordisk Investigational Site	Boise	Idaho
United States	Novo Nordisk Investigational Site	Boston	Massachusetts
United States	Novo Nordisk Investigational Site	Buffalo	New York
United States	Novo Nordisk Investigational Site	Columbus	Ohio
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Fargo	North Dakota
United States	Novo Nordisk Investigational Site	Gainesville	Florida
United States	Novo Nordisk Investigational Site	Idaho Falls	Idaho
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Las Vegas	Nevada
United States	Novo Nordisk Investigational Site	Lexington	Kentucky
United States	Novo Nordisk Investigational Site	Long Beach	California
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Mineola	New York
United States	Novo Nordisk Investigational Site	Minneapolis	Minnesota
United States	Novo Nordisk Investigational Site	Minneapolis	Minnesota
United States	Novo Nordisk Investigational Site	Neptune	New Jersey
United States	Novo Nordisk Investigational Site	Orlando	Florida
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania
United States	Novo Nordisk Investigational Site	Raleigh	North Carolina
United States	Novo Nordisk Investigational Site	Sacramento	California
United States	Novo Nordisk Investigational Site	Salt Lake City	Utah
United States	Novo Nordisk Investigational Site	Sioux Falls	South Dakota
United States	Novo Nordisk Investigational Site	Springfield	Illinois
United States	Novo Nordisk Investigational Site	Tallahassee	Florida
United States	Novo Nordisk Investigational Site	Tampa	Florida
United States	Novo Nordisk Investigational Site	Tucson	Arizona
United States	Novo Nordisk Investigational Site	Tulsa	Oklahoma
United States	Novo Nordisk Investigational Site	Ventura	California

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Bulgaria,  Czechia,  Estonia,  Finland,  Germany,  India,  Israel,  Italy,  Japan,  Latvia,  Lithuania,  Poland,  Puerto Rico,  Russian Federation,  Serbia,  Turkey,  Ukraine, 

References & Publications (1)

Bode BW, Iotova V, Kovarenko M, Laffel LM, Rao PV, Deenadayalan S, Ekelund M, Larsen SF, Danne T. Efficacy and Safety of Fast-Acting Insulin Aspart Compared With Insulin Aspart, Both in Combination With Insulin Degludec, in Children and Adolescents With Type 1 Diabetes: The onset 7 Trial. Diabetes Care. 2019 May 10. pii: dc190009. doi: 10.2337/dc19-0009. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Percentage of HbA1c	Change from baseline (week 0) in glycosylated haemoglobin (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 participant-site contact and included data collected after a subject discontinued trial product.	Week 0, Week 26
Secondary	Change in 8-point SMPG Profile: Mean PPG Over All Three Meals	Change from baseline (week 0) in mean post prandial glucose (PPG) over all three meals was evaluated after 26 weeks of randomisation. PPG for each meal (breakfast, lunch and main evening meal) was recorded by the participant as part of the 8-point self-measured plasma glucose (SMPG) profile. Mean PPG over all three meals was derived as the mean of all corresponding mean meal. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in 8-point SMPG Profile: PPG Increment Over All Three Meals	Change from baseline (week 0) in mean PPG increment over all three meals was evaluated after 26 weeks of randomisation. Postprandial glucose (PPG) increment for each meal (breakfast, lunch and main evening meal) was derived from the 8-point profile as the difference between PPG (1 hour after the meal) values and the plasma glucose (PG) value before meal. The mean of the derived increments was then calculated separately for each meal. Mean PPG increment over all three meals was derived as the mean of all corresponding mean meal increments. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in 8-point SMPG Profile: Individual Meal (Breakfast, Lunch and Main Evening Meal) PPG	Change from baseline (week 0) in individual meal (breakfast, lunch and main evening meal) PPG was evaluated after 26 weeks of randomisation. PPG for each meal was recorded by the participant as part of the 8-point SMPG profile. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in 8-point SMPG Profile: Individual Meal (Breakfast, Lunch and Main Evening Meal) PPG Increment	Change from baseline (week 0) in individual meal (breakfast, lunch and main evening meal) PPG increment was evaluated after 26 weeks of randomisation. PPG increment for each meal was derived from the 8-point profile as the difference between PPG values (1 hour after the meal) and the PG value before meal. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in 8-point SMPG Profile: Mean of the 8-point Profile	Change from baseline (week 0) in mean of the 8-point SMPG profile was evaluated after 26 weeks of randomisation. SMPG values were recorded at 8 time-points on two consecutive days: before and after (60 minute after the start of the meal) breakfast, lunch and main evening meal, before bedtime, and before breakfast on the next day. Mean of the 8-point profile was derived as the mean of all corresponding mean SMPG recorded at 8 different time points. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Fluctuation in the 8-point SMPG Profile	Fluctuation in the 8-point SMPG profile was evaluated after 26 weeks of randomisation. Fluctuation in 8-point SMPG profile was the average absolute difference from the mean of the SMPG profile. The results are based on the last in-trial value.	Week 26
Secondary	Change in FPG	Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated after 26 weeks of randomisation. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in 1,5-anhydroglucitol	Change from baseline (week 0) in 1,5-anhydroglucitol was evaluated after 26 weeks of randomisation. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Percentage of Subjects Reaching HbA1c Target (HbA1c Less Than 7.5 %) According to ISPAD Guidelines	Percentage of participants (yes/no) reaching HbA1c less than 7.5 % according to International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines was evaluated after 26 weeks of randomisation. The results are based on the last in-trial value.	Week 26
Secondary	Percentage of Subjects Reaching HbA1c Target (HbA1c Less Than 7.5 %) According to ISPAD Guidelines, Without Severe Hypoglycaemia	Percentage of participants (yes/no) reaching HbA1c less than 7.5 % according to ISPAD guidelines, without severe hypoglycaemia was evaluated after 26 weeks of randomisation. Severe hypoglycaemia according to ISPAD guidelines: hypoglycaemic episode associated with severe neuroglycopenia, usually resulting in coma or seizure and requiring parenteral therapy (glucagon or intravenous glucose). The results are based on the last in-trial value.	Week 26
Secondary	Insulin Dose (Units/Day): Total Basal	Total basal insulin dose (Units/day) was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period: the observation period from date of first dose of randomised NovoRapid®/NovoLog® / faster aspart and no later than 7 days after the day of last dose of NovoRapid®/NovoLog® / faster aspart. The on-treatment observation period includes data collected up to and including 7 days after treatment discontinuation. Number of participants analysed = number of participants contributed to the analysis. Analysis population description: Safety analysis set (SAS) included all participants receiving at least one dose of the investigational product (faster aspart) or its comparator (NovoRapid®/NovoLog®).	Week 26
Secondary	Insulin Dose (Units/Day): Total Bolus	Total bolus insulin dose (Units/day) was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 26
Secondary	Insulin Dose (Units/Day): Individual Meal Insulin Dose	Individual meal (breakfast, lunch and main evening meal) insulin dose (Units/day) was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value.	Week 26
Secondary	Insulin Dose (Units/kg/Day): Total Basal	Total basal insulin dose (Units/kg/day) was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 26
Secondary	Insulin Dose (Units/kg/Day): Total Bolus	Total bolus insulin dose (Units/kg/day) was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 26
Secondary	Insulin Dose (Units/kg/Day): Individual Meal Insulin Dose	Individual meal (breakfast, lunch and main evening meal) insulin dose (Units/kg/day) was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 26
Secondary	Change of Time Spent in Low Interstitial Glucose (IG) (IG <=3.9 mmol/L [70 mg/dL])	Change from baseline (week 0) in the time spent in low IG (<=3.9 mmol/L [70 mg/dL]) based on continuous glucose monitoring (CGM) was evaluated after 26 weeks of randomisation. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Incidence of Episodes With IG <=2.5, 3.0, 3.9 mmol/L (45, 54, 70 mg/dL) and IG >10.0, 12.0 mmol/L (180, 216 mg/dL)	Incidence of episodes (number of episodes per 24 hours) with IG <=2.5, 3.0, 3.9 mmol/L (45, 54, 70 mg/dL) and IG >10.0, 12.0 mmol/L (180, 216 mg/dL) based on CGM was calculated after 26 weeks of randomisation. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. The results are based on the last in-trial value.	Week 26
Secondary	Percentage of Time Spent With IG <=2.5, 3.0, 3.9 mmol/L (45, 54, 70 mg/dL) and IG >10.0, 12.0 mmol/L (180, 216 mg/dL)	Percentage of time spent with IG <=2.5, 3.0, 3.9 mmol/L (45, 54, 70 mg/dL) and IG >10.0, 12.0 mmol/L (180, 216 mg/dL) based on CGM was evaluated after 26 weeks of randomisation. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. The results are based on the last in-trial value.	Week 26
Secondary	Percentage of Time Spent Within IG Target 4.0-10.0 mmol/L (71-180 mg/dL) Both Included	Percentage of time spent within IG target 4.0-10.0 mmol/L (71-180 mg/dL), both included based on CGM was evaluated after 26 weeks of randomisation. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. The results are based on the last in-trial value.	Week 26
Secondary	Change in Mean IG Increment (0-1 Hours and 0-2 Hours After Start of the Meal)	Change from baseline (week 0) in mean IG increment (0-1 hours and 0-2 hours after start of the meal) based on CGM was evaluated after 26 weeks of randomisation. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. Presented values are mean of all the meals (breakfast, lunch and evening meal). The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in Mean IG Peak After Start of Meal	Change from baseline (week 0) in mean IG peak after start of meal based on CGM was evaluated after 26 weeks of randomisation. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. Presented values are mean of all the meals (breakfast, lunch and evening meal). The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in Mean Time to the IG Peak After Meal	Change from baseline (week 0) in mean time to the IG peak after meal based on CGM was evaluated after 26 weeks of randomisation. A subgroup of subjects wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. Presented values are mean of all the meals (breakfast, lunch and evening meal). The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in 30-minute PPG	Change from baseline (week 0) in 30-minute PPG based on meal test was evaluated after 26 weeks of randomisation. In connection to wearing the CGM for 11 to 13 days up to week 0 and up to week 26, the subgroup of participants had a standardised liquid meal test at the 2 visits, monitoring the PPG at 30-minute after the meal intake at the visit. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in 30-minute PPG Increment	Change from baseline (week 0) in 30-minute PPG increment based on meal test was evaluated after 26 weeks of randomisation. In connection to wearing the CGM for 11 to 13 days up to week 0 and up to week 26, the subgroup of participants had a standardised liquid meal test at the 2 visits, monitoring the pre-prandial glucose (before the meal) the PPG at 30-minute (after the meal) at the visit. PPG increment was derived as 30-minute PPG measurement minus the pre-prandial PG. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in 1-hour PPG	Change from baseline (week 0) in 1-hour PPG based on meal test was evaluated after 26 weeks of randomisation. In connection to wearing the CGM for 11 to 13 days up to week 0 and up to week 26, the subgroup of participants had a standardised liquid meal test at the 2 visits, monitoring the PPG at 1-hour after the meal intake at the visit. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in 1-hour PPG Increment	Change from baseline (week 0) in 1-hour PPG increment based on meal test was evaluated after 26 weeks of randomisation. In connection to wearing the CGM for 11 to 13 days up to week 0 and up to week 26, the subgroup of participants had a standardised liquid meal test at the 2 visits, monitoring the pre-prandial glucose (before the meal) the PPG at 1-hour (after the meal) at the visit. PPG increment was derived as 1-hour PPG measurement minus the pre-prandial PG. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in 2-hour PPG	Change from baseline (week 0) in 2-hour PPG based on meal test was evaluated after 26 weeks of randomisation. In connection to wearing the CGM for 11 to 13 days up to week 0 and up to week 26, the subgroup of participants had a standardised liquid meal test at the 2 visits, monitoring the PPG at 2-hour after the meal intake at the visit. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in 2-hour PPG Increment	Change from baseline (week 0) in 2-hour PPG increment based on meal test was evaluated after 26 weeks of randomisation. In connection to wearing the CGM for 11 to 13 days up to week 0 and up to week 26, the subgroup of participants had a standardised liquid meal test at the 2 visits, monitoring the pre-prandial glucose (before the meal) the PPG at 2-hour (after the meal) at the visit. PPG increment was derived as 2-hour PPG measurement minus the pre-prandial PG. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in AUCIG,0-15min	Change in area under the IG curve 0-15 minutes post meal (AUCIG,0-15min) during meal test and based on CGM measurements was evaluated after 26 weeks of randomisation. Interstitial glucose (IG) was measured every 5 minutes. The endpoint was calculated as the area under the IG curve using the trapezoidal method and weighted by duration. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in AUCIG,0-30min	Change in area under the IG curve 0-30 minutes post meal (AUCIG,0-30min) during meal test and based on CGM measurements was evaluated after 26 weeks of randomisation. IG was measured every 5 minutes. The endpoint was calculated as the area under the IG curve using the trapezoidal method and weighted by duration. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in AUCIG,0-1h	Change in area under the IG curve 0-1 hour post meal (AUCIG,0-1h) during meal test and based on CGM measurements was evaluated after 26 weeks of randomisation. IG was measured every 5 minutes. The endpoint was calculated as the area under the IG curve using the trapezoidal method and weighted by duration. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in AUCIG,0-2h	Change in area under the IG curve 0-2 hours post meal (AUCIG,0-2h) during meal test and based on CGM measurements was evaluated after 26 weeks of randomisation. IG was measured every 5 minutes. The endpoint was calculated as the area under the IG curve using the trapezoidal method and weighted by duration. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in AUCIG,0-4h	Change in area under the IG curve 0-4 hours post meal (AUCIG,0-4h) during meal test and based on CGM measurements was evaluated after 26 weeks of randomisation. IG was measured every 5 minutes. The endpoint was calculated as the area under the IG curve using the trapezoidal method and weighted by duration. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in Time to the IG Peak After Start of Meal	Change in time to the IG peak after start of meal during meal test and based on CGM measurements was evaluated after 26 weeks of randomisation. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. Presented values are mean of all the meals (breakfast, lunch and evening meal). The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Change in IG Peak After Start of Meal	Change in IG peak after start of meal during meal test and based on CGM measurements was evaluated after 26 weeks of randomisation. A subgroup of participants wore a CGM for between 11 and 13 days up to week 0 (randomisation) and up to week 26 to monitor their IG on a continuous basis. Presented values are mean of all the meals (breakfast, lunch and evening meal). The results are based on the last in-trial value.	Week 0, Week 26
Secondary	Number of Treatment Emergent Hypoglycaemic Episodes According to American Diabetes Association (ADA)/ISPAD Classification: Total	Treatment emergent: if the onset of the episode occurred on or after the first day of treatment with investigational medicinal product (IMP) after randomisation, and no later than 1 day after the last day on IMP. Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to ADA classification: 2) Documented symptomatic: episode during which typical symptoms of hypoglycaemia are accompanied by a PG level =3.9 mmol/L. 3) Asymptomatic: episode not accompanied by typical symptoms of hypoglycaemia, but with a PG level =3.9 mmol/L. 4) Probable symptomatic: an episode during which symptoms of hypoglycaemia are not accompanied by a PG determination but that was presumably caused by a PG level =3.9 mmol/L. 5) Pseudo-hypoglycaemia: episode during which the person with diabetes reports any of the typical symptoms of hypoglycaemia with a PG level >3.9mmol/L, but approaching that level. The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Hypoglycaemic Episodes According to ADA/ISPAD Classification: Daytime	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to ADA classification: 2) Documented symptomatic. 3) Asymptomatic. 4) Probable symptomatic. 5) Pseudo-hypoglycaemia. Daytime period: The period between 07:01 and 22:59 (both included). The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Hypoglycaemic Episodes According to ADA/ISPAD Classification: Nocturnal (23:00-7:00, Both Included)	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to ADA classification: 2) Documented symptomatic. 3) Asymptomatic. 4) Probable symptomatic. 5) Pseudo-hypoglycaemia. Nocturnal period: The period between 23:00 and 07:00 (both included). The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification: Total	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to Novo Nordisk classification: 2) Symptomatic blood glucose (BG) confirmed: episode that is BG confirmed by PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. 3) Asymptomatic BG confirmed: episode that is BG confirmed by PG value <3.1 mmol/L without symptoms consistent with hypoglycaemia. 4) Severe or BG confirmed symptomatic: an episode that is severe according to the ISPAD classification or BG confirmed by a PG value <3.1 mmol/L with symptoms consistent with hypoglycaemia. 5) BG confirmed: an episode that is BG confirmed by a PG value <3.1 mmol/L with or without symptoms consistent with hypoglycaemia. 6) Severe or BG confirmed: an episode that is severe according to the ISPAD Classification or BG confirmed by a PG value <3.1 mmol/L with or without symptoms consistent with hypoglycaemia. The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification: Daytime	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to Novo Nordisk classification: 2) BG confirmed. 3) Severe or BG confirmed symptomatic. 4) Severe or BG confirmed. 5) Asymptomatic BG confirmed. Daytime period: The period between 07:01 and 22:59 (both included). The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification: Nocturnal (23:00-7:00, Both Included)	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to Novo Nordisk classification: 2) BG confirmed. 3) Severe or BG confirmed symptomatic. 4) Severe or BG confirmed. 5) Asymptomatic BG confirmed. Nocturnal period: The period between 23:00 and 07:00 (both included). The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Meal Related (From Start of Meal Until 1 Hour After Start of Meal) Hypoglycaemic Episodes According to ADA/ISPAD Classification	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to ADA classification: 2) Documented symptomatic. 3) Asymptomatic. 4) Probable symptomatic. 5) Pseudo-hypoglycaemia. The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Meal Related (From Start of Meal Until 2 Hours After Start of Meal) Hypoglycaemic Episodes According to ADA/ISPAD Classification	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to ADA classification: 2) Documented symptomatic. 3) Asymptomatic. 4) Probable symptomatic. 5) Pseudo-hypoglycaemia. The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Meal Related (From Start of Meal Until 4 Hours After Start of Meal) Hypoglycaemic Episodes According to ADA/ISPAD Classification	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to ADA classification: 2) Documented symptomatic. 3) Asymptomatic. 4) Probable symptomatic. 5) Pseudo-hypoglycaemia. The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Meal Related (From 2-4 Hours After Start of Meal) Hypoglycaemic Episodes According to ADA/ISPAD Classification	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to ADA classification: 2) Documented symptomatic. 3) Asymptomatic. 4) Probable symptomatic. 5) Pseudo-hypoglycaemia. The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Meal Related (From Start of Meal Until 1 Hour After Start of Meal) Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to Novo Nordisk classification: 2) BG confirmed. 3) Severe or BG confirmed symptomatic. 4) Severe or BG confirmed. 5) Asymptomatic BG confirmed. The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Meal Related (From Start of Meal Until 2 Hours After Start of Meal) Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to Novo Nordisk classification: 2) BG confirmed. 3) Severe or BG confirmed symptomatic. 4) Severe or BG confirmed. 5) Asymptomatic BG confirmed. The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Meal Related (From Start of Meal Until 4 Hours After Start of Meal) Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to Novo Nordisk classification: 2) BG confirmed. 3) Severe or BG confirmed symptomatic. 4) Severe or BG confirmed. 5) Asymptomatic BG confirmed. The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Meal Related (From 2-4 Hours After Start of Meal) Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification	Classification of hypoglycaemia: 1) Severe (according to ISPAD classification). Following are according to Novo Nordisk classification: 2) BG confirmed. 3) Severe or BG confirmed symptomatic. 4) Severe or BG confirmed. 5) Asymptomatic BG confirmed. The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Adverse Events (AEs)	Treatment emergent was defined as an event that has onset up to 7 days after last day of IMP (faster aspart or NovoRapid®/NovoLog®) and excluding the events occurring in the run-in period. The results are based on the on-treatment period.	Week 0-26
Secondary	Number of Treatment Emergent Injection Site Reactions	Treatment emergent was defined as an event that has onset up to 7 days after last day of IMP and excluding the events occurring in the run-in period. The results are based on the on-treatment period.	Week 0-26
Secondary	Change in Physical Examination	The following physical examinations were done: 1) Cardiovascular system. 2) Central and peripheral nervous system. 3) Gastrointestinal system including the mouth. 4) General appearance. 5) Head, ears, eyes, nose, throat and neck. 6) Musculoskeletal system. 7) Respiratory system. 8) Skin. Presented results are number of participants with the following outcomes: normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS). Presented results are baseline (week 0) and last on-treatment values. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Vital Sign: Blood Pressure	Change from baseline (week 0) in blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)) was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value.	Week 0, Week 26
Secondary	Change in Vital Sign: Pulse	Change from baseline (week 0) in pulse was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value.	Week 0, Week 26
Secondary	Change in Body Weight	Change from baseline (week 0) in body weight was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Height	Change from baseline (week 0) in height was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Body Mass Index	Change from baseline (week 0) in body mass index (BMI) was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in SD Score of Body Weight	Change from baseline (week 0) in standard deviation (SD) score of body weight was evaluated after 26 weeks of randomisation. SD-scores are defined to be able to normalise the body weight in the various age groups. To estimate the growth of children, standardised weight is calculated for each year of age and for each sex. Thus, a child with a weight equal to the mean value for its age and sex has an SD score of 0, while a child with a weight 2 SDs above the mean value for its age and sex has an SD score of +2. The SD scores are derived from the age and sex of the subjects and the body weight together with growth curves defined for a reference population. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in SD Score of Body Mass Index	Change from baseline (week 0) in SD score of BMI was evaluated after 26 weeks of randomisation. SD scores for BMI were determined in a similar way as SD scores for weight by use of a suitable reference population based on age and sex. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Haematology: Haemoglobin	Change from baseline (week 0) in haemoglobin was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Haematology: Haematocrit	Change from baseline (week 0) in haematocrit was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Haematology: Erythrocytes	Change from baseline (week 0) in erythrocytes was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Haematology: Thrombocytes	Change from baseline (week 0) in thrombocytes was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Haematology: Leukocytes	Change from baseline (week 0) in leukocytes was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Biochemistry: Creatinine	Change from baseline (week 0) in creatinine was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Biochemistry: Alanine Aminotransferase (ALT)	Change from baseline (week 0) in ALT was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Biochemistry: Aspartate Aminotransferase (AST)	Change from baseline (week 0) in AST was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Biochemistry: Alkaline Phosphatase (AP)	Change from baseline (week 0) in AP was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Biochemistry: Sodium	Change from baseline (week 0) in sodium was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Biochemistry: Potassium	Change from baseline (week 0) in potassium was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Biochemistry: Albumin	Change from baseline (week 0) in albumin was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Biochemistry: Total Bilirubin	Change from baseline (week 0) in total bilirubin was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value. Number of participants analysed = number of participants contributed to the analysis.	Week 0, Week 26
Secondary	Change in Lipid Profile: Total Cholesterol	Change from baseline (week 0) in total cholesterol after 26 weeks of randomisation is presented as ratio to baseline values. The results are based on the last on-treatment value.	Week 0, Week 26
Secondary	Change in Lipid Profile: High Density Lipoproteins (HDL)	Change from baseline (week 0) in HDL after 26 weeks of randomisation is presented as ratio to baseline values. The results are based on the last on-treatment value.	Week 0, Week 26
Secondary	Change in Lipid Profile: Low Density Lipoproteins (LDL)	Change from baseline (week 0) in LDL after 26 weeks of randomisation is presented as ratio to baseline values. The results are based on the last on-treatment value.	Week 0, Week 26
Secondary	Change in Anti-insulin Aspart Antibody Development: Specific	Change from baseline (week 0) in 'antibodies specific for insulin aspart' was evaluated after 26 weeks of randomisation. This endpoint was measured as % bound radioactivity-labelled insulin aspart/Total added radioactivity-labelled insulin aspart (%B/T). The results are based on the last on-treatment value.	Week 0, Week 26
Secondary	Change in Anti-insulin Aspart Antibody Development: Cross-reacting With Human Insulin	Change from baseline (week 0) in 'antibodies for insulin aspart, those cross-reacting with human insulin' was evaluated after 26 weeks of randomisation. This endpoint was measured as % bound radioactivity-labelled insulin aspart/Total added radioactivity-labelled insulin aspart (%B/T). The results are based on the last on-treatment value.	Week 0, Week 26
Secondary	Change in Anti-insulin Aspart Antibody Development: Total	Change from baseline (week 0) in 'total anti-insulin aspart antibodies (specific for insulin aspart and those cross-reacting with human insulin)' was evaluated after 26 weeks of randomisation. This endpoint was measured as % bound radioactivity-labelled insulin aspart/Total added radioactivity-labelled insulin aspart (%B/T). The results are based on the last on-treatment value.	Week 0, Week 26

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