Comparison of NPH Insulin and Insulin Detemir in Children and Adolescents With Type 1 Diabetes
Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT00435019
Collaborator
(none)
348
43
2
19
8.1
0.4
Study Details
Study Description
Brief Summary
This trial is conducted in Europe.
The aim of this research is to compare the efficacy and safety of treatment with NPH insulin and insulin detemir. You will be treated with either insulin detemir or NPH insulin once or twice daily as basal insulin. Additionally you will receive insulin aspart as bolus insulin
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
348 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Efficacy and Safety Comparison of Insulin Detemir vs. NPH Insulin in Children and Adolescents Diagnosed With Type 1 Diabetes
Study Start Date
:
Feb 1, 2007
Actual Primary Completion Date
:
Sep 1, 2008
Actual Study Completion Date
:
Sep 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: insulin detemir insulin detemir + insulin aspart |
Drug: insulin detemir
s.c. injection, once or twice daily.
Drug: insulin aspart
s.c. injection, at main meals.
|
| Experimental: NPH insulin NPH insulin + insulin aspart |
Drug: insulin NPH
s.c. injection, once or twice daily.
Drug: insulin aspart
s.c. injection, at main meals.
|
Outcome Measures
Primary Outcome Measures
- Glycosylated Haemoglobin A1c (HbA1c) [after 52 weeks of treatment]
Glycosylated haemoglobin A1c (HbA1c) measured after 52 weeks of treatment and analysed by central laboratory.
Secondary Outcome Measures
- Number of Subjects Reporting Adverse Events [from week -2 to week 52]
Number of subjects reporting adverse events during the trial (from week -2 to week 52). For details, please refer to the adverse events section.
- Observed Insulin Antibody Values [at 0 and 52 weeks]
Observed insulin antibody values for insulin detemir specific antibodies, insulin aspart specific antibodies and insulin detemir/insulin aspart cross-reacting antibodies.
Eligibility Criteria
Criteria
Ages Eligible for Study:
2 Years
to 16 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Insulin detemir naive
-
Type 1 diabetes for at least 12 months
-
HbA1c lesser than or equal to 11.0%
Exclusion Criteria:
- Significant concomitant diseases
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novo Nordisk Investigational Site | Pleven | Bulgaria | 5800 | |
| 2 | Novo Nordisk Investigational Site | Sofia | Bulgaria | 1606 | |
| 3 | Novo Nordisk Investigational Site | Varna | Bulgaria | 9010 | |
| 4 | Novo Nordisk Investigational Site | Olomouc | Czech Republic | 77520 | |
| 5 | Novo Nordisk Investigational Site | Pardubice | Czech Republic | 53203 | |
| 6 | Novo Nordisk Investigational Site | Prague 5 | Czech Republic | 15018 | |
| 7 | Novo Nordisk Investigational Site | Glostrup | Denmark | 2600 | |
| 8 | Novo Nordisk Investigational Site | Kolding | Denmark | 6000 | |
| 9 | Novo Nordisk Investigational Site | Odense | Denmark | 5000 | |
| 10 | Novo Nordisk Investigational Site | Viborg | Denmark | 8800 | |
| 11 | Novo Nordisk Investigational Site | Espoo | Finland | 02740 | |
| 12 | Novo Nordisk Investigational Site | Helsinki | Finland | 00029 | |
| 13 | Novo Nordisk Investigational Site | Oulu | Finland | 90029 | |
| 14 | Novo Nordisk Investigational Site | Seinäjoki | Finland | 60220 | |
| 15 | Novo Nordisk Investigational Site | Tampere | Finland | 33520 | |
| 16 | Novo Nordisk Investigational Site | Turku | Finland | 20100 | |
| 17 | Novo Nordisk Investigational Site | ANGERS cedex 09 | France | 49033 | |
| 18 | Novo Nordisk Investigational Site | MONTPELLIER cedex 05 | France | 34295 | |
| 19 | Novo Nordisk Investigational Site | Paris | France | 75015 | |
| 20 | Novo Nordisk Investigational Site | Toulouse | France | 31059 | |
| 21 | Novo Nordisk Investigational Site | Budapest | Hungary | 1083 | |
| 22 | Novo Nordisk Investigational Site | Miskolc | Hungary | 3501 | |
| 23 | Novo Nordisk Investigational Site | Skopje | Macedonia, The Former Yugoslav Republic of | 1000 | |
| 24 | Novo Nordisk Investigational Site | Gdansk | Poland | 80-211 | |
| 25 | Novo Nordisk Investigational Site | Kielce | Poland | 25-734 | |
| 26 | Novo Nordisk Investigational Site | Siedlce | Poland | 08-110 | |
| 27 | Novo Nordisk Investigational Site | Warszawa | Poland | 00-576 | |
| 28 | Novo Nordisk Investigational Site | Warszawa | Poland | 01-184 | |
| 29 | Novo Nordisk Investigational Site | Warszawa | Poland | 04-730 | |
| 30 | Novo Nordisk Investigational Site | Moscow | Russian Federation | 117036 | |
| 31 | Novo Nordisk Investigational Site | Moscow | Russian Federation | 119049 | |
| 32 | Novo Nordisk Investigational Site | Moscow | Russian Federation | 125373 | |
| 33 | Novo Nordisk Investigational Site | Saint-Petersburg | Russian Federation | 191144 | |
| 34 | Novo Nordisk Investigational Site | Altunizade-Istanbul | Turkey | 34662 | |
| 35 | Novo Nordisk Investigational Site | Antalya | Turkey | 07059 | |
| 36 | Novo Nordisk Investigational Site | Istanbul | Turkey | 34093 | |
| 37 | Novo Nordisk Investigational Site | Izmir | Turkey | 35340 | |
| 38 | Novo Nordisk Investigational Site | Kayseri | Turkey | 38010 | |
| 39 | Novo Nordisk Investigational Site | Aberdeen | United Kingdom | AB25 2ZG | |
| 40 | Novo Nordisk Investigational Site | Birmingham | United Kingdom | B4 6NH | |
| 41 | Novo Nordisk Investigational Site | Cambridge | United Kingdom | CB2 2QQ | |
| 42 | Novo Nordisk Investigational Site | Dundee | United Kingdom | DD1 9SY | |
| 43 | Novo Nordisk Investigational Site | Norfolk | United Kingdom | NR4 7UY |
Sponsors and Collaborators
- Novo Nordisk A/S
Investigators
- Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00435019
Other Study ID Numbers:
- NN304-1689
- 2006-000051-18
First Posted:
Feb 14, 2007
Last Update Posted:
Mar 10, 2017
Last Verified:
Jan 1, 2017
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 35 centres in 11 countries. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Insulin Detemir | NPH Insulin |
|---|---|---|
| Arm/Group Description | Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals |
| Period Title: Overall Study | ||
| STARTED | 177 | 171 |
| Exposed to Study Drug | 177 | 170 |
| COMPLETED | 164 | 161 |
| NOT COMPLETED | 13 | 10 |
Baseline Characteristics
| Arm/Group Title | Insulin Detemir | NPH Insulin | Total |
|---|---|---|---|
| Arm/Group Description | Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | Total of all reporting groups |
| Overall Participants | 177 | 170 | 347 |
| Age (Count of Participants) | |||
| <=18 years |
177
100%
|
170
100%
|
347
100%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
10.0
(4.09)
|
9.8
(3.90)
|
9.9
(3.99)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
94
53.1%
|
73
42.9%
|
167
48.1%
|
| Male |
83
46.9%
|
97
57.1%
|
180
51.9%
|
Outcome Measures
| Title | Glycosylated Haemoglobin A1c (HbA1c) |
|---|---|
| Description | Glycosylated haemoglobin A1c (HbA1c) measured after 52 weeks of treatment and analysed by central laboratory. |
| Time Frame | after 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) is defined as all randomised subjects exposed to at least one dose of trial product with a postbaseline observation, classified according to randomised treatment. |
| Arm/Group Title | Insulin Detemir | NPH Insulin |
|---|---|---|
| Arm/Group Description | Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals |
| Measure Participants | 171 | 168 |
| Mean (Standard Error) [Percent (%) glycosylated haemoglobin] |
8.75
(0.11)
|
8.64
(0.11)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Insulin Detemir, NPH Insulin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | 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%. A sample size of 344 subjects, in total, with a drop-out rate of 20 percent would yield 274 subjects for evaluation of HbA1c. This would give 85 percent power to detect a difference in means of HbA1c of 0.4 percentage points assuming that the standard deviation was 1.1 using a two-sided t-test with a 0.05 significance level. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.12 | |
| Confidence Interval |
() 95% -0.12 to 0.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Subjects Reporting Adverse Events |
|---|---|
| Description | Number of subjects reporting adverse events during the trial (from week -2 to week 52). For details, please refer to the adverse events section. |
| Time Frame | from week -2 to week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set (SAS): all randomised subjects exposed to at least one dose of trial product, classified according to actual treatment. |
| Arm/Group Title | Insulin Detemir | NPH Insulin |
|---|---|---|
| Arm/Group Description | Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals |
| Measure Participants | 177 | 170 |
| Number [participants] |
132
74.6%
|
135
79.4%
|
| Title | Observed Insulin Antibody Values |
|---|---|
| Description | Observed insulin antibody values for insulin detemir specific antibodies, insulin aspart specific antibodies and insulin detemir/insulin aspart cross-reacting antibodies. |
| Time Frame | at 0 and 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set (SAS): All randomised subjects exposed to at least one dose of trial product, classified according to actual treatment. In some cases, antibody samples were taken earlier than required. These results were not included. A shipment of antibody samples was lost during transportation, and thus these antibody data were missing. |
| Arm/Group Title | Insulin Detemir | NPH Insulin |
|---|---|---|
| Arm/Group Description | Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals |
| Measure Participants | 177 | 170 |
| Insulin detemir specific, week 0 (n=127, 112) |
3.23
(1.03)
|
2.95
(1.23)
|
| Insulin detemir specific, week 52 (n=125, 128) |
5.15
(3.30)
|
3.01
(1.66)
|
| Cross-reacting insulin, week 0 (n=130, 113) |
27.06
(19.1)
|
27.26
(18.6)
|
| Cross-reacting insulin, week 52 (n=132, 135) |
43.70
(15.6)
|
30.19
(17.3)
|
| Insulin aspart specific, week 0 (n=126, 111) |
2.26
(2.32)
|
2.24
(2.99)
|
| Insulin aspart specific, week 52 (n=128, 133) |
4.20
(4.35)
|
2.68
(3.60)
|
Adverse Events
| Time Frame | Adverse events were collected from week 0 to week 52. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Insulin Detemir | NPH Insulin | ||
| Arm/Group Description | Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | ||
All Cause Mortality |
||||
| Insulin Detemir | NPH Insulin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Insulin Detemir | NPH Insulin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/177 (7.9%) | 20/170 (11.8%) | ||
| Gastrointestinal disorders | ||||
| Dyspepsia | 1/177 (0.6%) | 1 | 1/170 (0.6%) | 1 |
| Gastritis | 0/177 (0%) | 0 | 2/170 (1.2%) | 2 |
| Abdominal Pain | 1/177 (0.6%) | 1 | 0/170 (0%) | 0 |
| Infections and infestations | ||||
| Gastroenteritis | 4/177 (2.3%) | 4 | 2/170 (1.2%) | 2 |
| Viral Infection | 1/177 (0.6%) | 1 | 1/170 (0.6%) | 1 |
| Gastroenteritis Shigella | 1/177 (0.6%) | 1 | 0/170 (0%) | 0 |
| Gastroenteritis Viral | 0/177 (0%) | 0 | 1/170 (0.6%) | 1 |
| Laryngitis | 0/177 (0%) | 0 | 1/170 (0.6%) | 1 |
| Otitis Media Acute | 1/177 (0.6%) | 1 | 0/170 (0%) | 0 |
| Soft Tissue Infection | 1/177 (0.6%) | 1 | 0/170 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Burns Second Degree | 1/177 (0.6%) | 1 | 0/170 (0%) | 0 |
| Medication Error | 0/177 (0%) | 0 | 1/170 (0.6%) | 1 |
| Metabolism and nutrition disorders | ||||
| Diabetic Ketoacidosis | 3/177 (1.7%) | 3 | 4/170 (2.4%) | 4 |
| Hypoglycaemia | 1/177 (0.6%) | 1 | 3/170 (1.8%) | 3 |
| Diabetes Mellitus Inadequate Control | 1/177 (0.6%) | 1 | 1/170 (0.6%) | 1 |
| Hypoglycaemic Unconsciousness | 0/177 (0%) | 0 | 2/170 (1.2%) | 3 |
| Nervous system disorders | ||||
| Convulsion | 0/177 (0%) | 0 | 1/170 (0.6%) | 1 |
| Epilepsy | 0/177 (0%) | 0 | 1/170 (0.6%) | 1 |
| Renal and urinary disorders | ||||
| Nephropathy | 0/177 (0%) | 0 | 1/170 (0.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Adenoidal Hypertrophy | 0/177 (0%) | 0 | 1/170 (0.6%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Insulin Detemir | NPH Insulin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 131/177 (74%) | 134/170 (78.8%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 9/177 (5.1%) | 10 | 7/170 (4.1%) | 7 |
| Infections and infestations | ||||
| Nasopharyngitis | 75/177 (42.4%) | 147 | 81/170 (47.6%) | 179 |
| Pharyngitis | 19/177 (10.7%) | 29 | 15/170 (8.8%) | 16 |
| Upper Respiratory Tract Infection | 18/177 (10.2%) | 32 | 16/170 (9.4%) | 32 |
| Gastroenteritis | 15/177 (8.5%) | 20 | 12/170 (7.1%) | 13 |
| Influenza | 10/177 (5.6%) | 14 | 18/170 (10.6%) | 25 |
| Viral Infection | 12/177 (6.8%) | 14 | 14/170 (8.2%) | 17 |
| Bronchitis | 9/177 (5.1%) | 11 | 12/170 (7.1%) | 15 |
| Nervous system disorders | ||||
| Headache | 26/177 (14.7%) | 65 | 23/170 (13.5%) | 44 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Novo Nordisk acknowledges the Investigator's right to publish the entire results of the trial. Any such scientific paper, presentation, communication or other information concerning the investigation described in this protocol, must be submitted in writing to Novo Nordisk Trial Manager prior to submission for publication/presentation for comments. Comments will be given within four weeks from receipt of the manuscript.
Results Point of Contact
| Name/Title | Public Access to Clinical Trials |
|---|---|
| Organization | Novo Nordisk A/S |
| Phone | |
| clinicaltrials@novonordisk.com |
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00435019
Other Study ID Numbers:
- NN304-1689
- 2006-000051-18
First Posted:
Feb 14, 2007
Last Update Posted:
Mar 10, 2017
Last Verified:
Jan 1, 2017