Phase 3
Completed N=777
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 · Diabetes Mellitus, Type 1
Source: ClinicalTrials.gov NCT02670915 ↗
Enrolled (actual)
777
Serious AEs
3.5%
Results posted
Apr 2019
Primary outcomePrimary: Change in the Percentage of HbA1c — 7.57; 7.58; 7.53; 0.06 Percentage of HbA1c — p=<0.001
◆ Published Evidence
Established
67citations · ~10 / year
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.
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.
Linked Publications
-
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in the Percentage of HbA1c |
7.57; 7.58; 7.53; 0.06; 0.33; 0.23 | <0.001 sig |
| SECONDARY Change in 8-point SMPG Profile: Mean PPG Over All Three Meals |
10.19; 10.12; 10.03; -0.94; 0.36; -0.21 | — |
| SECONDARY Change in 8-point SMPG Profile: PPG Increment Over All Three Meals |
1.20; 1.01; 0.97; -0.92; 0.56; 0.14 | — |
| SECONDARY Change in 8-point SMPG Profile: Individual Meal (Breakfast, Lunch and Main Evening Meal) PPG |
10.51; 10.51; 10.49; -1.11; 0.16; 0.04 | — |
| SECONDARY Change in 8-point SMPG Profile: Individual Meal (Breakfast, Lunch and Main Evening Meal) PPG Increment |
1.90; 2.10; 2.12; -0.82; 0.46; 0.10 | — |
| SECONDARY Change in 8-point SMPG Profile: Mean of the 8-point Profile |
9.41; 9.47; 9.39; -0.27; 0.17; -0.05 | — |
| SECONDARY Fluctuation in the 8-point SMPG Profile |
1.88; 1.94; 1.83 | — |
| SECONDARY Change in FPG |
7.58; 8.03; 7.79; 0.41; -0.08; -0.13 | — |
| SECONDARY Change in 1,5-anhydroglucitol |
4.95; 5.07; 5.13; -0.06; -0.85; -0.63 | — |
| SECONDARY Percentage of Subjects Reaching HbA1c Target (HbA1c Less Than 7.5 %) According to ISPAD Guidelines |
42.3; 31.7; 39.5; 57.7; 68.3; 60.5 | — |
| SECONDARY Percentage of Subjects Reaching HbA1c Target (HbA1c Less Than 7.5 %) According to ISPAD Guidelines, Without Severe Hypoglycaemia |
41.9; 30.9; 38.4; 58.1; 69.1; 61.6 | — |
| SECONDARY Insulin Dose (Units/Day): Total Basal |
21.6; 21.5; 20.7 | — |
| SECONDARY Insulin Dose (Units/Day): Total Bolus |
23.3; 23.5; 22.5 | — |
| SECONDARY Insulin Dose (Units/Day): Individual Meal Insulin Dose |
7.3; 7.1; 6.8; 8.1; 8.4; 7.9 | — |
| SECONDARY Insulin Dose (Units/kg/Day): Total Basal |
0.433; 0.425; 0.409 | — |
| SECONDARY Insulin Dose (Units/kg/Day): Total Bolus |
0.483; 0.491; 0.468 | — |
| SECONDARY Insulin Dose (Units/kg/Day): Individual Meal Insulin Dose |
0.151; 0.150; 0.144; 0.170; 0.174; 0.166 | — |
| SECONDARY Change of Time Spent in Low Interstitial Glucose (IG) (IG <=3.9 mmol/L [70 mg/dL]) |
107.94; 100.70; 81.52; -24.11; -13.06; 6.92 | — |
| 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) |
0.55; 0.68; 0.57; 1.01; 1.10; 1.03 | — |
| 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) |
1.09; 1.80; 1.34; 2.19; 2.90; 2.48 | — |
| SECONDARY Percentage of Time Spent Within IG Target 4.0-10.0 mmol/L (71-180 mg/dL) Both Included |
53.00; 52.56; 51.03 | — |
| SECONDARY Change in Mean IG Increment (0-1 Hours and 0-2 Hours After Start of the Meal) |
0.56; 0.73; 0.61; -0.19; 0.26; 0.07 | — |
| SECONDARY Change in Mean IG Peak After Start of Meal |
12.90; 12.92; 12.90; -0.28; 0.80; 0.38 | — |
| SECONDARY Change in Mean Time to the IG Peak After Meal |
103.16; 106.21; 102.20; 4.70; -8.56; 2.29 | — |
| SECONDARY Change in 30-minute PPG |
11.28; 10.96; 11.71; -0.21; 1.84; -0.45 | — |
| SECONDARY Change in 30-minute PPG Increment |
3.44; 3.48; 4.02; 0.36; 1.92; -0.34 | — |
| SECONDARY Change in 1-hour PPG |
12.77; 12.56; 13.06; -0.15; 2.54; -0.63 | — |
| SECONDARY Change in 1-hour PPG Increment |
4.93; 5.08; 5.36; 0.42; 2.63; -0.52 | — |
| SECONDARY Change in 2-hour PPG |
12.50; 12.54; 12.37; 0.69; 1.80; -0.75 | — |
| SECONDARY Change in 2-hour PPG Increment |
4.66; 5.06; 4.67; 1.26; 1.62; -0.64 | — |
| SECONDARY Change in AUCIG,0-15min |
8.01; 7.49; 7.66; -1.27; 0.08; -0.53 | — |
| SECONDARY Change in AUCIG,0-30min |
8.28; 7.80; 8.13; -1.15; 0.22; -0.47 | — |
| SECONDARY Change in AUCIG,0-1h |
9.63; 9.43; 10.02; -0.87; 0.54; -0.65 | — |
| SECONDARY Change in AUCIG,0-2h |
11.40; 11.48; 11.76; -0.84; 0.75; -0.86 | — |
| SECONDARY Change in AUCIG,0-4h |
11.21; 11.19; 11.46; -0.38; 0.62; -1.30 | — |
| SECONDARY Change in Time to the IG Peak After Start of Meal |
102.85; 94.26; 93.80; 5.29; -0.04; -8.76 | — |
| SECONDARY Change in IG Peak After Start of Meal |
14.87; 15.15; 15.11; -0.55; 1.11; -1.36 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to American Diabetes Association (ADA)/ISPAD Classification: Total |
3; 8; 4; 5391; 5712; 5170 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to ADA/ISPAD Classification: Daytime |
3; 5; 3; 4895; 5077; 4779 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to ADA/ISPAD Classification: Nocturnal (23:00-7:00, Both Included) |
0; 3; 1; 496; 635; 391 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification: Total |
3; 8; 4; 3580; 3586; 3272 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification: Daytime |
3; 5; 3; 3184; 3112; 2960 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification: Nocturnal (23:00-7:00, Both Included) |
0; 3; 1; 396; 474; 312 | — |
| 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 |
0; 0; 0; 178; 113; 157 | — |
| 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 |
2; 1; 1; 1125; 882; 1016 | — |
| 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 |
3; 1; 2; 3041; 3064; 2812 | — |
| SECONDARY Number of Treatment Emergent Meal Related (From 2-4 Hours After Start of Meal) Hypoglycaemic Episodes According to ADA/ISPAD Classification |
1; 0; 1; 1916; 2182; 1796 | — |
| 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 |
0; 0; 0; 119; 66; 105 | — |
| 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 |
2; 1; 1; 715; 504; 600 | — |
| 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 |
3; 1; 2; 1774; 1781; 1666 | — |
| SECONDARY Number of Treatment Emergent Meal Related (From 2-4 Hours After Start of Meal) Hypoglycaemic Episodes According to Novo Nordisk/ISPAD Classification |
1; 0; 1; 1059; 1277; 1066 | — |
| SECONDARY Number of Treatment Emergent Adverse Events (AEs) |
576; 678; 593 | — |
| SECONDARY Number of Treatment Emergent Injection Site Reactions |
11; 31; 17 | — |
| SECONDARY Change in Physical Examination |
260; 254; 258; 1; 4; 0 | — |
| SECONDARY Change in Vital Sign: Blood Pressure |
106.4; 107.0; 106.8; 0.8; 1.5; 1.1 | — |
| SECONDARY Change in Vital Sign: Pulse |
80.6; 80.5; 79.4; -0.6; 0.3; 0.7 | — |
| SECONDARY Change in Body Weight |
46.69; 46.48; 46.28; 2.21; 1.90; 2.15 | — |
| SECONDARY Change in Height |
1.50; 1.50; 1.50; 0.02; 0.02; 0.02 | — |
| SECONDARY Change in Body Mass Index |
19.68; 19.67; 19.64; 0.37; 0.28; 0.34 | — |
| SECONDARY Change in SD Score of Body Weight |
0.349; 0.351; 0.361; 0.034; 0.008; 0.030 | — |
| SECONDARY Change in SD Score of Body Mass Index |
0.296; 0.298; 0.317; 0.016; 0.004; 0.007 | — |
| SECONDARY Change in Haematology: Haemoglobin |
8.33; 8.47; 8.41; 0.08; 0.09; 0.09 | — |
| SECONDARY Change in Haematology: Haematocrit |
40.87; 41.51; 41.34; 0.45; 0.40; 0.32 | — |
| SECONDARY Change in Haematology: Erythrocytes |
4.81; 4.87; 4.88; 0.02; 0.04; 0.02 | — |
| SECONDARY Change in Haematology: Thrombocytes |
268.1; 270.0; 262.5; 1.2; 1.6; 6.0 | — |
| SECONDARY Change in Haematology: Leukocytes |
6.10; 6.10; 6.11; 0.08; 0.14; 0.10 | — |
| SECONDARY Change in Biochemistry: Creatinine |
51.8; 52.6; 52.1; 1.1; 1.5; 1.7 | — |
| SECONDARY Change in Biochemistry: Alanine Aminotransferase (ALT) |
14.4; 14.7; 14.8; 0.1; 1.3; 0.5 | — |
| SECONDARY Change in Biochemistry: Aspartate Aminotransferase (AST) |
19.9; 20.0; 20.5; 0.1; 1.1; -0.4 | — |
| SECONDARY Change in Biochemistry: Alkaline Phosphatase (AP) |
212.7; 209.8; 226.2; -3.0; -1.7; -2.8 | — |
| SECONDARY Change in Biochemistry: Sodium |
139.5; 139.6; 139.7; 0.5; 0.3; 0.04 | — |
| SECONDARY Change in Biochemistry: Potassium |
4.48; 4.52; 4.52; 0.02; -0.06; 0.01 | — |
| SECONDARY Change in Biochemistry: Albumin |
4.47; 4.51; 4.50; 0.01; 0.01; 0.005 | — |
| SECONDARY Change in Biochemistry: Total Bilirubin |
7.9; 7.9; 8.0; 0.2; 0.2; 0.3 | — |
| SECONDARY Change in Lipid Profile: Total Cholesterol |
0.989; 1.023; 1.016 | — |
| SECONDARY Change in Lipid Profile: High Density Lipoproteins (HDL) |
1.004; 1.030; 1.023 | — |
| SECONDARY Change in Lipid Profile: Low Density Lipoproteins (LDL) |
1.014; 1.040; 1.041 | — |
| SECONDARY Change in Anti-insulin Aspart Antibody Development: Specific |
1.436; 1.459; 1.183; -0.099; -0.213; -0.201 | — |
| SECONDARY Change in Anti-insulin Aspart Antibody Development: Cross-reacting With Human Insulin |
18.794; 21.576; 20.156; -3.202; -4.845; -3.802 | — |
| SECONDARY Change in Anti-insulin Aspart Antibody Development: Total |
20.230; 23.044; 21.344; -3.271; -5.061; -4.004 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02670915) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.