Trial Outcomes & Findings for Comparison of Insulin Detemir and Insulin Aspart in 2 Separate Injections Twice Daily to Extemporaneous Mixing Injection Regimen Twice Daily - The Paediatric Mixing Trial (NCT NCT00542620)

NCT ID: NCT00542620

Last Updated: 2014-11-03

Results Overview

Measured for the Per Protocol (PP) set

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

25 participants

Primary outcome timeframe

Week 0 and Week 8

Results posted on

2014-11-03

Participant Flow

Four centres in France

Children with type 1 diabetes currently treated with insulin detemir and insulin aspart and with a good glycaemic control. At trial entry, subjects must be 6-18 years old with a HbA1c (glycosylated haemoglobin) below or equal to 8.6%

Participant milestones

Participant milestones
Measure
Mixed Injection
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Overall Study
STARTED
13
12
Overall Study
Exposed to Drug
12
13
Overall Study
COMPLETED
13
12
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of Insulin Detemir and Insulin Aspart in 2 Separate Injections Twice Daily to Extemporaneous Mixing Injection Regimen Twice Daily - The Paediatric Mixing Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Total
n=25 Participants
Total of all reporting groups
Age, Continuous
11.6 years
STANDARD_DEVIATION 2.6 • n=93 Participants
10.9 years
STANDARD_DEVIATION 2.5 • n=4 Participants
11.3 years
STANDARD_DEVIATION 2.5 • n=27 Participants
Sex: Female, Male
Female
5 Participants
n=93 Participants
7 Participants
n=4 Participants
12 Participants
n=27 Participants
Sex: Female, Male
Male
8 Participants
n=93 Participants
5 Participants
n=4 Participants
13 Participants
n=27 Participants
Region of Enrollment
France
13 participants
n=93 Participants
12 participants
n=4 Participants
25 participants
n=27 Participants
Diabetes history
6.68 years
STANDARD_DEVIATION 3.51 • n=93 Participants
6.13 years
STANDARD_DEVIATION 2.38 • n=4 Participants
6.42 years
STANDARD_DEVIATION 2.97 • n=27 Participants

PRIMARY outcome

Timeframe: Week 0 and Week 8

Population: Per Protocol (PP) analysis set consists of all the ITT (Intention-to-Treat) subjects who did not present any significant protocol deviations that could potentially affect the efficacy results. One subject was excluded from PP as subject received separate injections despite being randomised to receive mixed injections.

Measured for the Per Protocol (PP) set

Outcome measures

Outcome measures
Measure
Mixed Injection
n=12 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Glycosylated Haemoglobin A1c (HbA1c)
Week 0
8.00 percentage of total haemoglobin
Standard Deviation 0.54
7.77 percentage of total haemoglobin
Standard Deviation 0.55
Glycosylated Haemoglobin A1c (HbA1c)
Week 8
7.63 percentage of total haemoglobin
Standard Deviation 0.55
8.15 percentage of total haemoglobin
Standard Deviation 0.57

PRIMARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

Measured for the ITT (Intention-to-Treat) set

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Glycosylated Haemoglobin A1c (HbA1c)
Week 0
7.93 percentage of total haemoglobin
Standard Deviation 0.57
7.77 percentage of total haemoglobin
Standard Deviation 0.55
Glycosylated Haemoglobin A1c (HbA1c)
Week 8
7.65 percentage of total haemoglobin
Standard Deviation 0.53
8.15 percentage of total haemoglobin
Standard Deviation 0.57

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Fructosamine
Week 0, n=13, 12
334.8 mmol/L
Standard Deviation 35.9
319.8 mmol/L
Standard Deviation 22.6
Fructosamine
Week 8, n=12, 12
316.4 mmol/L
Standard Deviation 30.1
334.8 mmol/L
Standard Deviation 41.9

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Self-measured Plasma Glucose Profile (Before Breakfast)
Week 0
190.31 mg/dL
Standard Deviation 56.80
165.39 mg/dL
Standard Deviation 70.28
Self-measured Plasma Glucose Profile (Before Breakfast)
Week 8
162.96 mg/dL
Standard Deviation 57.46
204.75 mg/dL
Standard Deviation 59.25

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

Outcome measures

Outcome measures
Measure
Mixed Injection
n=5 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=7 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Self-measured Plasma Glucose Profile (After Breakfast)
Week 0, n=5, 6
123.00 mg/dL
Standard Deviation 61.9
164.89 mg/dL
Standard Deviation 73.33
Self-measured Plasma Glucose Profile (After Breakfast)
Week 8, n=4, 7
208.08 mg/dL
Standard Deviation 48.19
167.98 mg/dL
Standard Deviation 70.64

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Self-measured Plasma Glucose Profile (Before Dinner)
Week 0
199.14 mg/dL
Standard Deviation 42.05
201.44 mg/dL
Standard Deviation 57.50
Self-measured Plasma Glucose Profile (Before Dinner)
Week 8
185.23 mg/dL
Standard Deviation 66.30
181.03 mg/dL
Standard Deviation 68.41

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation. CGMS® data not available/sufficient for pre-study evaluation in five subjects or at post-study evaluation in four subjects.

Outcome measures

Outcome measures
Measure
Mixed Injection
n=8 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=6 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Self-measured Plasma Glucose Profile (After Dinner)
Week 0, n=8, 5
175.38 mg/dL
Standard Deviation 58.47
201.80 mg/dL
Standard Deviation 59.12
Self-measured Plasma Glucose Profile (After Dinner)
Week 8, n=7, 6
198.00 mg/dL
Standard Deviation 53.85
187.67 mg/dL
Standard Deviation 85.63

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2 hours (hrs), T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Cmax of Free Insulin
Week 0
216 pmol/L
Standard Deviation 542.4
167 pmol/L
Standard Deviation 130.4
Pharmacokinetics: Cmax of Free Insulin
Week 8
274 pmol/L
Standard Deviation 109.2
186 pmol/L
Standard Deviation 105.5

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Tmax of Free Insulin
Week 0
2.5 hours
Standard Deviation 0.74
3.0 hours
Standard Deviation 0.98
Pharmacokinetics: Tmax of Free Insulin
Week 8
2.5 hours
Standard Deviation 0.8
1.8 hours
Standard Deviation 0.72

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Free Insulin
Week 0
638.4 pmol.h/L
Standard Deviation 1022.95
398.9 pmol.h/L
Standard Deviation 395.19
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Free Insulin
Week 8
819.6 pmol.h/L
Standard Deviation 310.41
466.2 pmol.h/L
Standard Deviation 266.93

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation. CGMS® data not available/sufficient for pre-study evaluation in five subjects or at post-study evaluation in four subjects.

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=11 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=11 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Free Insulin
Week 0, n=8, 9
1441.3 pmol.h/L
Standard Deviation 7516.22
752.1 pmol.h/L
Standard Deviation 4128.04
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Free Insulin
Week 8, n=11, 11
1981.1 pmol.h/L
Standard Deviation 1442.49
672.8 pmol.h/L
Standard Deviation 7156.05

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation. CGMS® data not available/sufficient for pre-study evaluation in five subjects or at post-study evaluation in four subjects

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=11 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=11 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Free Insulin
Week 0, n=8, 9
3.6 hours
Standard Deviation 17.84
2.3 hours
Standard Deviation 10.93
Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Free Insulin
Week 8, n=11, 11
2.9 hours
Standard Deviation 3.34
2.0 hours
Standard Deviation 11.62

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Cmax of Insulin Detemir
Week 8
12000 pmol/L
Standard Deviation 23807.2
12600 pmol/L
Standard Deviation 8426.6
Pharmacokinetics: Cmax of Insulin Detemir
Week 0
10700 pmol/L
Standard Deviation 25149.9
10500 pmol/L
Standard Deviation 6840.2

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Tmax of Insulin Detemir
Week 0
3.5 hours
Standard Deviation 0.93
3.5 hours
Standard Deviation 0.48
Pharmacokinetics: Tmax of Insulin Detemir
Week 8
3.5 hours
Standard Deviation 0.38
3.3 hours
Standard Deviation 0.78

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Detemir
Week 0
36591.2 pmol.h/L
Standard Deviation 70709.5
34653.4 pmol.h/L
Standard Deviation 21243.3
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Detemir
Week 8
36055.0 pmol.h/L
Standard Deviation 73609.6
39757.0 pmol.h/L
Standard Deviation 23076.5

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation. CGMS® data not available/sufficient for pre-study evaluation in five subjects or at post-study evaluation in four subjects

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=4 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=6 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Detemir
Week 8, n=3, 6
123555.7 pmol.h/L
Standard Deviation 141207.72
362313.5 pmol.h/L
Standard Deviation 4287360.41
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Detemir
Week 0, n=4, 3
230728.2 pmol.h/L
Standard Deviation 304790.62
68509.6 pmol.h/L
Standard Deviation 116350.34

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. CGMS® data not available/sufficient for pre-study evaluation in five subjects or at post-study evaluation in four subjects

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=4 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=6 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Detemir
Week 0, n=4, 3
16.2 hours
Standard Deviation 4.12
8.2 hours
Standard Deviation 6.53
Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Detemir
Week 8, n=3, 6
5.6 hours
Standard Deviation 4.2
20.8 hours
Standard Deviation 249.57

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Cmax of Insulin Aspart
Week 0
557 pmol/L
Standard Deviation 2784.2
762 pmol/L
Standard Deviation 378.3
Pharmacokinetics: Cmax of Insulin Aspart
Week 8
662 pmol/L
Standard Deviation 576.3
601 pmol/L
Standard Deviation 355.3

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Tmax of Insulin Aspart
Week 0
2 hours
Standard Deviation 0.99
2 hours
Standard Deviation 0.97
Pharmacokinetics: Tmax of Insulin Aspart
Week 8
2 hours
Standard Deviation 0.53
1.5 hours
Standard Deviation 0.51

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Aspart
Week 8
2102.4 pmol.h/L
Standard Deviation 1378.73
1540 pmol.h/L
Standard Deviation 894.4
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Aspart
Week 0
1546.3 pmol.h/L
Standard Deviation 3163.27
1510.9 pmol.h/L
Standard Deviation 963.37

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Aspart
Week 0, n=10, 11
3008.1 pmol.h/L
Standard Deviation 7689.04
3006.3 pmol.h/L
Standard Deviation 4458.12
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Aspart
Week 8, n=13, 12
5674.3 pmol.h/L
Standard Deviation 10668.8
3019.9 pmol.h/L
Standard Deviation 1013.19

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Aspart
Week 0, n=10, 11
2.2 hours
Standard Deviation 6.75
2 hours
Standard Deviation 3.09
Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Aspart
Week 8, n=13, 12
3.5 hours
Standard Deviation 41.88
1.7 hours
Standard Deviation 1.62

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

Z score of weight. To estimate the growth of children, standardised mean weight values were calculated for each month of age and for each sex

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Weight Z Score
Week 0, n=13, 12
-0.42 Z-score
Standard Deviation 0.71
0.19 Z-score
Standard Deviation 0.69
Weight Z Score
Week 8, n=11, 12
-0.29 Z-score
Standard Deviation 0.65
0.26 Z-score
Standard Deviation 0.67

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.

Z score of BMI index. To estimate the growth of children, standardised mean BMI values were calculated for each month of age and for each sex

Outcome measures

Outcome measures
Measure
Mixed Injection
n=13 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=12 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Body Mass Index (BMI) Z Score
Week 0, n=13, 12
-0.32 Z-score
Standard Deviation 0.63
0.04 Z-score
Standard Deviation 0.86
Body Mass Index (BMI) Z Score
Week 8, n=11, 12
-0.07 Z-score
Standard Deviation 0.52
0.26 Z-score
Standard Deviation 0.73

SECONDARY outcome

Timeframe: Weeks 0-8

Population: All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subjects are analysed based on treatments actually received.

Number of hypoglycaemic episodes from Week 0 to Week 8, defined as self-measurement plasma glucose less than 56 mg/dL (3.1 mmol/L). Classified as major, minor or symptoms only. Major if unable to treat her/himself (given the age of the study population, the definition of major hypoglycemia was to be adapted through the investigator's judgment). Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L (56 mg/dL). Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.

Outcome measures

Outcome measures
Measure
Mixed Injection
n=12 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=13 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Incidence of Hypoglycaemic Episodes - All Episodes
351 episodes
293 episodes

SECONDARY outcome

Timeframe: Weeks 0-8

Population: All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subjects are analysed based on treatments actually received.

Number of minor hypoglycaemic episodes from Week 0 to Week 8, defined as self-measurement plasma glucose below 3.1 mmol/L (56 mg/dL) and the child is able to treat her/himself.

Outcome measures

Outcome measures
Measure
Mixed Injection
n=12 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=13 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Incidence of Hypoglycaemic Episodes - Glycaemia Below 0.56 g/L
With symptoms
68 episodes
159 episodes
Incidence of Hypoglycaemic Episodes - Glycaemia Below 0.56 g/L
Without (w/o) symptoms
75 episodes
48 episodes
Incidence of Hypoglycaemic Episodes - Glycaemia Below 0.56 g/L
W/o info on presence of symptoms
23 episodes
6 episodes

SECONDARY outcome

Timeframe: Weeks 0-8

Population: All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subjects are analysed based on treatments actually received.

Number of "symptoms only" hypoglycaemic episodes from Week 0 to Week 8, defined as self-measurement plasma glucose higher than or equal to 3.1 mmol/L (56 mg/dL) or no plasma glucose measurement and the child is able to treat her/himself.

Outcome measures

Outcome measures
Measure
Mixed Injection
n=12 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=13 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Incidence of Hypoglycaemic Episodes - Glycaemia Above or Equal to 0.56 g/L
W/o information on presence of symptoms
5 episodes
1 episodes
Incidence of Hypoglycaemic Episodes - Glycaemia Above or Equal to 0.56 g/L
With symptoms
49 episodes
46 episodes
Incidence of Hypoglycaemic Episodes - Glycaemia Above or Equal to 0.56 g/L
Without (w/o) symptoms
131 episodes
33 episodes

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subjects are analysed based on treatments actually received.

Via a paper diary, the children perceived insulin therapy injection pain by using a four-grade facial visual analogue scale (VAS): very sad face, sad face, happy face or very happy face.

Outcome measures

Outcome measures
Measure
Mixed Injection
n=12 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=13 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Percentage of Children Assessing Insulin Therapy Injection Pain as "Sad Face"
Week 0
45 percentage of subjects
33 percentage of subjects
Percentage of Children Assessing Insulin Therapy Injection Pain as "Sad Face"
Week 8
0 percentage of subjects
23 percentage of subjects

SECONDARY outcome

Timeframe: Week 0 and week 8

Population: All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subjects are analysed based on treatments actually received.

Via a paper diary, the children perceived insulin therapy injection pain by using a four-grade facial visual analogue scale (VAS): very sad face, sad face, happy face or very happy face.

Outcome measures

Outcome measures
Measure
Mixed Injection
n=12 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=13 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Percentage of Children Assessing Insulin Therapy Injection Pain as "Happy Face"
Week 8
81 percentage of subjects
69 percentage of subjects
Percentage of Children Assessing Insulin Therapy Injection Pain as "Happy Face"
Week 0
27 percentage of subjects
50 percentage of subjects

SECONDARY outcome

Timeframe: Week 0 and Week 8

Population: All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subjects are analysed based on treatments actually received.

Via a paper diary, the children perceived insulin therapy injection pain by using a four-grade facial visual analogue scale (VAS): very sad face, sad face, happy face or very happy face.

Outcome measures

Outcome measures
Measure
Mixed Injection
n=12 Participants
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=13 Participants
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Percentage of Children Assessing Insulin Therapy Injection Pain as "Very Happy Face"
Week 0
27.3 percentage of subjects
16.7 percentage of subjects
Percentage of Children Assessing Insulin Therapy Injection Pain as "Very Happy Face"
Week 8
18.2 percentage of subjects
7.7 percentage of subjects

Adverse Events

Mixed Injection

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Separate Injection

Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Mixed Injection
n=12 participants at risk
Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Separate Injection
n=13 participants at risk
Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed
Infections and infestations
Rhinitis
8.3%
1/12 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
15.4%
2/13 • Number of events 2 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Infections and infestations
Gastroenteritis
8.3%
1/12 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
7.7%
1/13 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Infections and infestations
Bronchitis
8.3%
1/12 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
0.00%
0/13 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Infections and infestations
Enterobiasis
0.00%
0/12 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
7.7%
1/13 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Infections and infestations
Nasopharyngitis
0.00%
0/12 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
7.7%
1/13 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Infections and infestations
Viral infection
8.3%
1/12 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
0.00%
0/13 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Gastrointestinal disorders
Abdominal pain
0.00%
0/12 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
23.1%
3/13 • Number of events 3 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
General disorders
Injection site reaction
0.00%
0/12 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
7.7%
1/13 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
General disorders
Pyrexia
0.00%
0/12 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
7.7%
1/13 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Surgical and medical procedures
Orthodontic procedure
0.00%
0/12 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
7.7%
1/13 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Surgical and medical procedures
Tooth extraction
8.3%
1/12 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
0.00%
0/13 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Eye disorders
Conjunctivitis allergic
8.3%
1/12 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
0.00%
0/13 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Injury, poisoning and procedural complications
Fall
0.00%
0/12 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
7.7%
1/13 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Reproductive system and breast disorders
Gynaecomastia
0.00%
0/12 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
7.7%
1/13 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
0.00%
0/12 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
7.7%
1/13 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
Skin and subcutaneous tissue disorders
Eczema
8.3%
1/12 • Number of events 1 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.
0.00%
0/13 • Adverse events are collected during treatment period (8 weeks)
All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subnjects are analysed based on treatments actually received.

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Results disclosure agreements

  • Principal investigator is a sponsor employee The Steering Committee has the right to publish the entire results of the trial. Any such scientific paper, presentation, communication, or other information concerning the investigation must be approved by the Steering Committee, and copies submitted in writing to Novo Nordisk prior to submission for publication/presentation for comments. Comments will be given within four weeks from receipt of the manuscript.
  • Publication restrictions are in place

Restriction type: OTHER