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

Phase 3

Completed

Conditions: Diabetes Mellitus, Type 1
Diabetes

Interventions: Drug: Faster-acting insulin aspart
Drug: insulin aspart
Drug: insulin degludec

Registration Number: NCT02670915

Lead Sponsor: Novo Nordisk A/S

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 834

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Post-meal faster-acting insulin aspart and insulin degludec	Faster-acting insulin aspart	-
Meal-time faster-acting insulin aspart and insulin degludec	Faster-acting insulin aspart	-
Meal-time faster-acting insulin aspart and insulin degludec	insulin degludec	-
Meal-time NovoRapid® (insulin aspart) and insulin degludec	insulin aspart	-
Meal-time NovoRapid® (insulin aspart) and insulin degludec	insulin degludec	-
Post-meal faster-acting insulin aspart and insulin degludec	insulin degludec	-

Primary Outcome Measures

Name	Time	Method
Change in the Percentage of HbA1c	Week 0, Week 26	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.

Secondary Outcome Measures

Name	Time	Method
Insulin Dose (Units/kg/Day): Total Bolus	Week 26	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.
Insulin Dose (Units/kg/Day): Individual Meal Insulin Dose	Week 26	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.
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)	Week 26	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.
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)	Week 26	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.
Change in 8-point SMPG Profile: PPG Increment Over All Three Meals	Week 0, Week 26	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.
Change in 30-minute PPG	Week 0, Week 26	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.
Change in 8-point SMPG Profile: Mean PPG Over All Three Meals	Week 0, Week 26	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.
Fluctuation in the 8-point SMPG Profile	Week 26	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.
Change in 8-point SMPG Profile: Individual Meal (Breakfast, Lunch and Main Evening Meal) PPG	Week 0, Week 26	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.
Change in 8-point SMPG Profile: Individual Meal (Breakfast, Lunch and Main Evening Meal) PPG Increment	Week 0, Week 26	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.
Change in 1,5-anhydroglucitol	Week 0, Week 26	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.
Percentage of Subjects Reaching HbA1c Target (HbA1c Less Than 7.5 %) According to ISPAD Guidelines	Week 26	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.
Percentage of Subjects Reaching HbA1c Target (HbA1c Less Than 7.5 %) According to ISPAD Guidelines, Without Severe Hypoglycaemia	Week 26	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.
Insulin Dose (Units/Day): Total Basal	Week 26	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®).
Insulin Dose (Units/Day): Total Bolus	Week 26	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.
Change of Time Spent in Low Interstitial Glucose (IG) (IG <=3.9 mmol/L [70 mg/dL])	Week 0, Week 26	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.
Change in 8-point SMPG Profile: Mean of the 8-point Profile	Week 0, Week 26	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.
Change in FPG	Week 0, Week 26	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.
Insulin Dose (Units/Day): Individual Meal Insulin Dose	Week 26	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.
Insulin Dose (Units/kg/Day): Total Basal	Week 26	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.
Percentage of Time Spent Within IG Target 4.0-10.0 mmol/L (71-180 mg/dL) Both Included	Week 26	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.
Change in Mean IG Increment (0-1 Hours and 0-2 Hours After Start of the Meal)	Week 0, Week 26	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.
Change in Mean IG Peak After Start of Meal	Week 0, Week 26	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.
Change in 30-minute PPG Increment	Week 0, Week 26	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.
Change in 2-hour PPG	Week 0, Week 26	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.
Change in 2-hour PPG Increment	Week 0, Week 26	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.
Change in AUCIG,0-30min	Week 0, Week 26	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.
Change in AUCIG,0-2h	Week 0, Week 26	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.
Change in AUCIG,0-4h	Week 0, Week 26	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.
Change in Mean Time to the IG Peak After Meal	Week 0, Week 26	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.
Change in 1-hour PPG	Week 0, Week 26	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.
Change in 1-hour PPG Increment	Week 0, Week 26	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.
Change in AUCIG,0-1h	Week 0, Week 26	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.
Number of Treatment Emergent Meal Related (From Start of Meal Until 1 Hour After Start of Meal) Hypoglycaemic Episodes According to ADA/ISPAD Classification	Week 0-26	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.
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	Week 0-26	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.
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	Week 0-26	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.
Change in SD Score of Body Mass Index	Week 0, Week 26	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.
Change in Haematology: Thrombocytes	Week 0, Week 26	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.
Change in AUCIG,0-15min	Week 0, Week 26	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.
Change in Time to the IG Peak After Start of Meal	Week 0, Week 26	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.
Change in IG Peak After Start of Meal	Week 0, Week 26	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.
Number of Treatment Emergent Hypoglycaemic Episodes According to American Diabetes Association (ADA)/ISPAD Classification: Total	Week 0-26	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.
Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification: Total	Week 0-26	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.
Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification: Daytime	Week 0-26	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.
Number of Treatment Emergent Meal Related (From Start of Meal Until 2 Hours After Start of Meal) Hypoglycaemic Episodes According to ADA/ISPAD Classification	Week 0-26	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.
Number of Treatment Emergent Meal Related (From 2-4 Hours After Start of Meal) Hypoglycaemic Episodes According to ADA/ISPAD Classification	Week 0-26	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.
Number of Treatment Emergent Meal Related (From 2-4 Hours After Start of Meal) Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification	Week 0-26	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.
Number of Treatment Emergent Adverse Events (AEs)	Week 0-26	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.
Change in Vital Sign: Blood Pressure	Week 0, Week 26	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.
Change in Vital Sign: Pulse	Week 0, Week 26	Change from baseline (week 0) in pulse was evaluated after 26 weeks of randomisation. The results are based on the last on-treatment value.
Number of Treatment Emergent Hypoglycaemic Episodes According to ADA/ISPAD Classification: Daytime	Week 0-26	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.
Number of Treatment Emergent Hypoglycaemic Episodes According to ADA/ISPAD Classification: Nocturnal (23:00-7:00, Both Included)	Week 0-26	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.
Change in Physical Examination	Week 0, Week 26	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.
Change in Body Weight	Week 0, Week 26	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.
Change in Body Mass Index	Week 0, Week 26	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.
Change in Haematology: Haemoglobin	Week 0, Week 26	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.
Change in Biochemistry: Aspartate Aminotransferase (AST)	Week 0, Week 26	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.
Change in Lipid Profile: Total Cholesterol	Week 0, Week 26	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.
Change in Lipid Profile: High Density Lipoproteins (HDL)	Week 0, Week 26	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.
Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification: Nocturnal (23:00-7:00, Both Included)	Week 0-26	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.
Number of Treatment Emergent Meal Related (From Start of Meal Until 4 Hours After Start of Meal) Hypoglycaemic Episodes According to ADA/ISPAD Classification	Week 0-26	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.
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	Week 0-26	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.
Number of Treatment Emergent Injection Site Reactions	Week 0-26	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.
Change in Height	Week 0, Week 26	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.
Change in SD Score of Body Weight	Week 0, Week 26	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.
Change in Haematology: Haematocrit	Week 0, Week 26	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.
Change in Haematology: Erythrocytes	Week 0, Week 26	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.
Change in Haematology: Leukocytes	Week 0, Week 26	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.
Change in Biochemistry: Creatinine	Week 0, Week 26	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.
Change in Biochemistry: Alanine Aminotransferase (ALT)	Week 0, Week 26	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.
Change in Biochemistry: Alkaline Phosphatase (AP)	Week 0, Week 26	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.
Change in Biochemistry: Sodium	Week 0, Week 26	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.
Change in Biochemistry: Albumin	Week 0, Week 26	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.
Change in Anti-insulin Aspart Antibody Development: Specific	Week 0, Week 26	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.
Change in Anti-insulin Aspart Antibody Development: Cross-reacting With Human Insulin	Week 0, Week 26	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.
Change in Biochemistry: Potassium	Week 0, Week 26	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.
Change in Biochemistry: Total Bilirubin	Week 0, Week 26	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.
Change in Lipid Profile: Low Density Lipoproteins (LDL)	Week 0, Week 26	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.
Change in Anti-insulin Aspart Antibody Development: Total	Week 0, Week 26	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.