Clinical Trial Results:
A 52-Week, Multinational, Multi-Centre, Open-Labelled, Randomised, Parallel, Efficacy and Safety Comparison of Insulin Detemir and NPH Insulin in Children and Adolescents 2-16 years with Type 1 Diabetes on a Basal-Bolus Regimen with Insulin Aspart as Bolus Insulin
Summary
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EudraCT number |
2006-000051-18 |
Trial protocol |
HU FI CZ DK BG FR |
Global end of trial date |
03 Sep 2008
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Mar 2016
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First version publication date |
31 Jul 2015
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NN304-1689
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00435019 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Novo Nordisk A/S
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Sponsor organisation address |
Novo Allé, Bagsvaerd, Denmark, 2880
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Public contact |
Global Clinical Registry (GCR, 1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Scientific contact |
Global Clinical Registry (GCR, 1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000412-PIP01-08 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Oct 2009
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Sep 2008
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Sep 2008
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the glycaemic control, measured as HbA1c, of insulin detemir administered once or twice daily plus mealtime insulin aspart with NPH insulin administered once or twice daily plus mealtime insulin aspart in children and adolescents with type 1 diabetes.
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Protection of trial subjects |
The trial was conducted in accordance with the Declaration of Helsinki (October 2000, amended 2002 and 2004) and ICH Good Clinical Practice (01-May-1996).
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Background therapy |
Not applicable. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
12 Feb 2007
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 19
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Country: Number of subjects enrolled |
Finland: 18
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Country: Number of subjects enrolled |
France: 6
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Country: Number of subjects enrolled |
Czech Republic: 38
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Country: Number of subjects enrolled |
Hungary: 28
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Country: Number of subjects enrolled |
Bulgaria: 38
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Country: Number of subjects enrolled |
Macedonia, the former Yugoslav Republic of: 24
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Country: Number of subjects enrolled |
Poland: 50
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Country: Number of subjects enrolled |
Russian Federation: 82
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Country: Number of subjects enrolled |
Turkey: 31
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Country: Number of subjects enrolled |
United Kingdom: 13
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Worldwide total number of subjects |
347
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EEA total number of subjects |
210
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
221
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Adolescents (12-17 years) |
126
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 35 centres in 11 countries: 3 in Bulgaria, 3 in the Czech Republic, 3 in Denmark, 5 in Finland, 2 in France, 2 in Hungary, 1 in Macedonia, 4 in Poland, 4 in the Russian Federation, 4 in Turkey and 4 in the UK. | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Not applicable. | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||
Blinding implementation details |
Not applicable.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Insulin detemir | |||||||||||||||||||||||||||
Arm description |
Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Insulin detemir
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Investigational medicinal product code |
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Other name |
Insulin detemir
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
s.c. injection, once or twice daily
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Investigational medicinal product name |
Insulin aspart
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Investigational medicinal product code |
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Other name |
Insulin aspart
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
s.c. injection, at main meals
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Arm title
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NPH Insulin | |||||||||||||||||||||||||||
Arm description |
Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
NPH insulin
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Investigational medicinal product code |
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Other name |
insulin human
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
s.c. injection, once or twice daily
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Investigational medicinal product name |
Insulin aspart
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Investigational medicinal product code |
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Other name |
Insulin aspart
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
s.c. injection, at main meals
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Baseline characteristics reporting groups
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Reporting group title |
Insulin detemir
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Reporting group description |
Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NPH Insulin
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Reporting group description |
Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Insulin detemir
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Reporting group description |
Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | ||
Reporting group title |
NPH Insulin
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Reporting group description |
Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals |
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End point title |
Glycosylated haemoglobin A1c (HbA1c), at the end of trial. | ||||||||||||
End point description |
Glycosylated haemoglobin A1c (HbA1c) measured after 52 weeks of treatment and analysed by central laboratory.
N = number of subject participated; N (detemir) = 171 and N (NPH) = 168
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End point type |
Primary
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End point timeframe |
After 52 weeks of treatment
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Notes [1] - Full analysis set for Insulin detemir arm has 177 subjects. [2] - Full analysis set for NPH Insulin arm has 170 subjects. |
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Insulin detemir v NPH Insulin
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Number of subjects included in analysis |
347
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.12
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.12 | ||||||||||||
upper limit |
0.36 | ||||||||||||
Notes [3] - The null hypothesis for the non-inferiority test was that the mean HbA1c with insulin detemir was greater than or equal to the mean HbA1c with NPH insulin plus 0.4%. |
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End point title |
Insulin detemir specific, insulin aspart specific and insulin detemir/aspart cross-reacting antibodies during treatment. | ||||||||||||||||||||||||||||||
End point description |
Insulin detemir specific antibodies, insulin aspart specific antibodies and insulin detemir/insulin aspart cross-reacting antibodies during 52 weeks of treatment.
N = number of subject participated.
1. Insulin detemir specific, week 0 , N (detemir) = 127, N (NPH) = 112 and week 52, N (detemir) =125, N (NPH)=128. 2. Cross-reacting insulin, week 0, N (detemir) = 130, N (NPH) = 113 and week 52, N (detemir) =132, N (NPH)=135. 3. Insulin aspart specific, week 0 N (detemir) = 126, N (NPH) = 111 and week 52, N (detemir) = 128, N (NPH) =133.
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End point type |
Secondary
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End point timeframe |
During 52 weeks of treatment
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Notes [4] - Safety analysis set for Insulin detemir arm has 177 subjects. [5] - safety analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
Fasting plasma glucose (FPGlab), end of trial | ||||||||||||
End point description |
Fasting plasma glucose (FPGlab), measured after 52 weeks of treatment and analysed by central laboratory.
N = number of subject participated. N (detemir) = 171, N (NPH) = 168.
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment
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Notes [6] - Full analysis set for Insulin detemir arm has 177 subjects. [7] - Full analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
9-points plasma glucose (PG) profile, end of trial | |||||||||||||||||||||||||||||||||||||||
End point description |
9-points plasma glucose (PG) profile, after 52 weeks of treatment
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment
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Notes [8] - Full analysis set for Insulin detemir arm has 177 subjects. [9] - Full analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
Nocturnal plasma glucose, end of trial | ||||||||||||
End point description |
Nocturnal plasma glucose after 52 weeks of treatment.
N = number of subject participated. N (detemir) = 125, N (NPH) = 132
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment.
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Notes [10] - Full analysis set for Insulin detemir arm has 177 subjects. [11] - Full analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
Body weight (kg), end of trial. | ||||||||||||
End point description |
Body weight (kg) after 52 weeks of treatment.
N = number of subject participated
N (detemir) = 172, N (NPH) = 166
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment
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Notes [12] - Safety analysis set for Insulin detemir arm has 177 subjects. [13] - Safety analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
Body mass index (BMI), end of trial | ||||||||||||
End point description |
Body mass index (BMI), after 52 weeks of treatment.
N = number of subject participated.
N (detemir) = 172, N (NPH) = 166
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment
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Notes [14] - Safety analysis set for Insulin detemir arm has 177 subjects. [15] - Safety analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
SD-score (Z-score) for body weight, end of trial | ||||||||||||
End point description |
SD-score (Z-score) for body weight, after 52 weeks of treatment.
N = number of subject participated.
N (detemir) = 172, N (NPH) = 166
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment
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Notes [16] - Safety analysis set for Insulin detemir arm has 177 subjects. [17] - Safety analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
Safety laboratory parameters haematology, end of trial | ||||||||||||||||||
End point description |
Safety laboratory parameters haematology, after 52 weeks of treatment.
N = number of subject participated.
N (detemir): Blood leukocytes, N = 168; Blood thrombocytes, N = 169
N (NHP): Blood leukocytes, N = 163; Blood thrombocytes, N = 160
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment
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Notes [18] - Safety analysis set for Insulin detemir arm has 177 subjects. [19] - Safety analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
Safety laboratory parameters haematology and biochemistry, end of trial | |||||||||||||||||||||
End point description |
Safety laboratory parameters haematology and biochemistry, after 52 weeks of treatment
N = number of subject participated.
N (detemir): Blood haemoglobin, serum sodium and serum potassium, N = 169
N (NPH): Blood haemoglobin, N = 163; serum sodium, N = 166; serum potassium, N = 166
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment
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Notes [20] - Safety analysis set for Insulin detemir arm has 177 subjects. [21] - Safety analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
Safety laboratory parameters biochemistry, end of trial | ||||||||||||||||||
End point description |
Safety laboratory parameters biochemistry, after 52 weeks of treatment.
N = number of subject participated.
N (detemir) = 169 and N (NPH) = 166
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment
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Notes [22] - Safety analysis set for Insulin detemir arm has 177 subjects. [23] - Safety analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
Safety laboratory parameters biochemistry, end of trial | |||||||||||||||||||||
End point description |
Safety laboratory parameters biochemistry, after 52 weeks of treatment.
N = number of subject participated.
N (detemir) = 169 and N (NPH) = 166
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment
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Notes [24] - Safety analysis set for Insulin detemir arm has 177 subjects. [25] - Safety analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
Occurrence of ketoacidosis requiring hospitalisation during treatment | |||||||||
End point description |
Occurrence of ketoacidosis requiring hospitalisation during 52 weeks of treatment
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End point type |
Secondary
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End point timeframe |
During 52 weeks of treatment
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Notes [26] - Safety analysis set for Insulin detemir arm has 177 subjects. [27] - Safety analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
Insulin detemir dose, at end of trial [28] | ||||||||||||
End point description |
Insulin detemir dose after 52 weeks of treatment.
N = number of subject participated; N (detemir) = 134
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment
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Notes [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only insulin detemir arm is presented here as the unit of measurement for it is U/kg. The other arm has different unit of measurement so it could not be possible to present both arms together. |
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Notes [29] - Safety analysis set for Insulin detemir arm has 177 subjects. |
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No statistical analyses for this end point |
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End point title |
Injection pain assessment using a facial visual analogue scale (VAS), at end-of-trial. | ||||||||||||
End point description |
Injection pain assessment using a facial visual analogue scale (VAS), during 52 weeks of treatment.
Visual Analogue Scale (VAS) range = 0 to 100; from no pain (0) to the worst possible pain (100).
N = number of subject participated; N (detemir) = 133 and N (NPH) = 138
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment
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Notes [30] - Safety analysis set for Insulin detemir arm has 177 subjects. [31] - Safety analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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End point title |
Vital signs, end of trial | ||||||||||||||||||
End point description |
Vital signs after 52 weeks of treatment.
N = number of subject participated. Mean blood pressure-systolic, N (detemir) = 171 and N (NPH) = 163. Mean blood pressure-diastolic, N (detemir) = 171 and N (NPH) = 163. Mean pulse, N (detemir) = 170 and N (NPH) = 164
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End point type |
Secondary
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End point timeframe |
After 52 weeks of treatment
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|||||||||||||||||||
Notes [32] - Safety analysis set for Insulin detemir arm has 177 subjects. [33] - Safety analysis set for NPH Insulin arm has 170 subjects. |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Incidence of all 24 hours hypoglycaemia (mild, moderate or severe) episodes during treatment | ||||||||||||||||||
End point description |
Incidence of all 24 hours hypoglycaemia (mild, moderate or severe) episodes during 52 weeks of treatment.
Detemir: 3 severe episodes were reported by 3 subjects; 370 moderate episodes were reported by 30 subjects; 5956 mild episodes were reported by 148 subjects.
NPH: 15 severe episodes were reported by 12 subjects; 947 moderate episodes were reported by 28 subjects; 7189 mild episodes were reported by 151 subjects.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
During 52 weeks of treatment
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [34] - Safety analysis set for Insulin detemir arm has 177 subjects. [35] - Safety analysis set for NPH Insulin arm has 170 subjects. |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Incidence of daytime hypoglycaemia (mild, moderate or severe) episodes during treatment | ||||||||||||||||||
End point description |
Incidence of daytime hypoglycaemia (mild, moderate or severe) episodes during treatment.
Detemir: 3 severe episodes were reported by 3 subjects; 311 moderate episodes were reported by 27 subjects; 5244 mild episodes were reported by146 subjects.
NPH: 9 severe episodes were reported by 8 subjects; 835 moderate episodes were reported by 27 subjects; 6050 mild episodes were reported by150 subjects.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
During 52 weeks of treatment
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [36] - Safety analysis set for Insulin detemir arm has 177 subjects. [37] - Safety analysis set for NPH Insulin arm has 170 subjects. |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Incidence of nocturnal hypoglycaemia (mild, moderate or severe) episodes during treatment | ||||||||||||||||||
End point description |
Incidence of nocturnal hypoglycaemia (mild, moderate or severe) episodes during 52 weeks of treatment.
Detemir: No severe episodes were reported; 59 moderate episodes were reported by 15 subjects; 712 mild episodes were reported by100 subjects.
NPH: 6 severe episodes were reported by 5 subjects; 112 moderate episodes were reported by 14 subjects; 1139 mild episodes were reported by111 subjects.
|
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End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
During 52 weeks of treatment
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [38] - Safety analysis set for Insulin detemir arm has 177 subjects. [39] - Safety analysis set for NPH Insulin arm has 170 subjects. |
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Safety laboratory parameter biochemistry, end of trial | |||||||||||||||
End point description |
Safety laboratory parameter biochemistry, after 52 weeks of treatment.
N = number of subject participated; N (detemir) = 169 and N (NPH) = 166
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
After 52 weeks of treatment
|
|||||||||||||||
|
||||||||||||||||
Notes [40] - Safety analysis set for Insulin detemir arm has 177 subjects. [41] - Safety analysis set for NPH Insulin arm has 170 subjects. |
||||||||||||||||
No statistical analyses for this end point |
|
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End point title |
Insulin NPH dose at the end of trial [42] | ||||||||||||
End point description |
Insulin NPH dose after 52 weeks of treatment.
N = number of subject participated; N (NPH) = 140
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
After 52 weeks of treatment
|
||||||||||||
Notes [42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only NPH insulin arm is presented here as the unit of measurement for it is IU/kg. The other arm has different unit of measurement so it could not be possible to present both arms together. |
|||||||||||||
|
|||||||||||||
Notes [43] - Safety analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
|
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End point title |
Adverse events during treatment | |||||||||
End point description |
Adverse events reported during 52 weeks of treatment.
Detemir: 537 adverse events were reported by 132 subjects
NPH: 554 adverse events were reported by 135 subjects
|
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End point type |
Secondary
|
|||||||||
End point timeframe |
During 52 weeks of treatment.
|
|||||||||
|
||||||||||
Notes [44] - Safety analysis set for Insulin detemir arm has 177 subjects. [45] - Safety analysis set for NPH Insulin arm has 170 subjects. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were collected from week 0 to week 52.
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Adverse event reporting additional description |
Safety analysis set (SAS): all randomised subjects exposed to at least one dose of trial product, classified according to actual treatment
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.1
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Reporting groups
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Reporting group title |
Insulin detemir
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Reporting group description |
Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NPH Insulin
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Reporting group description |
Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
11 Sep 2006 |
Global substantial amendment 1: The NN304-1689 trial was planned as a post approval commitment trial requested by the EU Authorities to follow the insulin antibody formation in children between 6 and 16 years. Since then, the protocol has developed to include a trial population down to 2 years. As insulin detemir is not yet approved for children below 6 years, the phase of the trial should be changed to phase 3b. |
||
12 Dec 2006 |
Global substantial amendment 2:
1.1 Insulin Antibodies.
To determine insulin detemir specific antibodies, insulin aspart specific antibodies and insulin detemir/aspart cross-reacting antibodies, a blood sample will be obtained at baseline (Visit 2) and at Visits 8, 9, 10. To minimise assay interference from excess insulin detemir, NPH insulin, aspart insulin, blood should be collected, when the blood levels of these drugs are the lowest. The most optimal time would be immediately before dinner and before injecting pre-dinner insulin aspart. For practical purposes, blood sampling should take place in the afternoon at least 3 hours after the pre-lunch insulin aspart injection and the following data should be recorded: • Date, time and dose of last basal insulin dose prior to blood sampling • Date, time and dose of last bolus insulin dose prior to blood sampling
• Date and time of blood sample
1.2 Clinical Supplies IV/WRS Management
Due to the introduction of Clinical Supplies IV/WRS (Interactive Voice/Web Response System) Management (CSIM) the protocol has been updated to be in accordance with the CSIM procedures.
In addition the Trial Materials section has been updated to correspond with new standards of wording. Finally, the text has been updated and it is now correctly stated, that NPH insulin can be
kept for 6 weeks, after the seal has been broken. There will be no changes with regards to trial design, subject treatment or methods/assessments. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
|||
http://www.ncbi.nlm.nih.gov/pubmed/21418455 |