Trial Outcomes & Findings for Comparison of NPH Insulin and Insulin Detemir in Children and Adolescents With Type 1 Diabetes (NCT NCT00435019)

NCT ID: NCT00435019

Last Updated: 2017-03-10

Results Overview

Glycosylated haemoglobin A1c (HbA1c) measured after 52 weeks of treatment and analysed by central laboratory.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

348 participants

Primary outcome timeframe

after 52 weeks of treatment

Results posted on

2017-03-10

Participant Flow

A total of 35 centres in 11 countries.

Participant milestones

Participant milestones
Measure	Insulin Detemir Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals	NPH Insulin Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals
Overall Study STARTED	177	171
Overall Study Exposed to Study Drug	177	170
Overall Study COMPLETED	164	161
Overall Study NOT COMPLETED	13	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin Detemir Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals	NPH Insulin Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals
Overall Study Adverse Event	1	0
Overall Study Lack of Efficacy	1	2
Overall Study Protocol Violation	3	1
Overall Study Personal reasons for withdrawal	8	7

Baseline Characteristics

Comparison of NPH Insulin and Insulin Detemir in Children and Adolescents With Type 1 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin Detemir n=177 Participants Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals	NPH Insulin n=170 Participants Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals	Total n=347 Participants Total of all reporting groups
Age, Categorical <=18 years	177 Participants n=5 Participants	170 Participants n=7 Participants	347 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	10.0 years STANDARD_DEVIATION 4.09 • n=5 Participants	9.8 years STANDARD_DEVIATION 3.90 • n=7 Participants	9.9 years STANDARD_DEVIATION 3.99 • n=5 Participants
Sex: Female, Male Female	94 Participants n=5 Participants	73 Participants n=7 Participants	167 Participants n=5 Participants
Sex: Female, Male Male	83 Participants n=5 Participants	97 Participants n=7 Participants	180 Participants n=5 Participants

PRIMARY outcome

Timeframe: after 52 weeks of treatment

Population: 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.

Glycosylated haemoglobin A1c (HbA1c) measured after 52 weeks of treatment and analysed by central laboratory.

Outcome measures

Outcome measures
Measure	Insulin Detemir n=171 Participants Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals	NPH Insulin n=168 Participants Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals
Glycosylated Haemoglobin A1c (HbA1c)	8.75 Percent (%) glycosylated haemoglobin Standard Error 0.11	8.64 Percent (%) glycosylated haemoglobin Standard Error 0.11

SECONDARY outcome

Timeframe: from week -2 to week 52

Population: Safety analysis set (SAS): all randomised subjects exposed to at least one dose of trial product, classified according to actual treatment.

Number of subjects reporting adverse events during the trial (from week -2 to week 52). For details, please refer to the adverse events section.

Outcome measures

Outcome measures
Measure	Insulin Detemir n=177 Participants Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals	NPH Insulin n=170 Participants Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals
Number of Subjects Reporting Adverse Events	132 participants	135 participants

SECONDARY outcome

Timeframe: at 0 and 52 weeks

Population: 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.

Observed insulin antibody values for insulin detemir specific antibodies, insulin aspart specific antibodies and insulin detemir/insulin aspart cross-reacting antibodies.

Outcome measures

Outcome measures
Measure	Insulin Detemir n=177 Participants Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals	NPH Insulin n=170 Participants Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals
Observed Insulin Antibody Values Insulin detemir specific, week 52 (n=125, 128)	5.15 Percent bound of total Standard Deviation 3.30	3.01 Percent bound of total Standard Deviation 1.66
Observed Insulin Antibody Values Cross-reacting insulin, week 0 (n=130, 113)	27.06 Percent bound of total Standard Deviation 19.1	27.26 Percent bound of total Standard Deviation 18.6
Observed Insulin Antibody Values Cross-reacting insulin, week 52 (n=132, 135)	43.70 Percent bound of total Standard Deviation 15.6	30.19 Percent bound of total Standard Deviation 17.3
Observed Insulin Antibody Values Insulin aspart specific, week 0 (n=126, 111)	2.26 Percent bound of total Standard Deviation 2.32	2.24 Percent bound of total Standard Deviation 2.99
Observed Insulin Antibody Values Insulin aspart specific, week 52 (n=128, 133)	4.20 Percent bound of total Standard Deviation 4.35	2.68 Percent bound of total Standard Deviation 3.60
Observed Insulin Antibody Values Insulin detemir specific, week 0 (n=127, 112)	3.23 Percent bound of total Standard Deviation 1.03	2.95 Percent bound of total Standard Deviation 1.23

Adverse Events

Insulin Detemir

Serious events: 14 serious events

Other events: 131 other events

Deaths: 0 deaths

NPH Insulin

Serious events: 20 serious events

Other events: 134 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Insulin Detemir n=177 participants at risk Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals	NPH Insulin n=170 participants at risk Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals
Infections and infestations Nasopharyngitis	42.4% 75/177 • Number of events 147 • Adverse events were collected from week 0 to week 52.	47.6% 81/170 • Number of events 179 • Adverse events were collected from week 0 to week 52.
Infections and infestations Pharyngitis	10.7% 19/177 • Number of events 29 • Adverse events were collected from week 0 to week 52.	8.8% 15/170 • Number of events 16 • Adverse events were collected from week 0 to week 52.
Infections and infestations Upper Respiratory Tract Infection	10.2% 18/177 • Number of events 32 • Adverse events were collected from week 0 to week 52.	9.4% 16/170 • Number of events 32 • Adverse events were collected from week 0 to week 52.
Infections and infestations Gastroenteritis	8.5% 15/177 • Number of events 20 • Adverse events were collected from week 0 to week 52.	7.1% 12/170 • Number of events 13 • Adverse events were collected from week 0 to week 52.
Infections and infestations Influenza	5.6% 10/177 • Number of events 14 • Adverse events were collected from week 0 to week 52.	10.6% 18/170 • Number of events 25 • Adverse events were collected from week 0 to week 52.
Infections and infestations Viral Infection	6.8% 12/177 • Number of events 14 • Adverse events were collected from week 0 to week 52.	8.2% 14/170 • Number of events 17 • Adverse events were collected from week 0 to week 52.
Infections and infestations Bronchitis	5.1% 9/177 • Number of events 11 • Adverse events were collected from week 0 to week 52.	7.1% 12/170 • Number of events 15 • Adverse events were collected from week 0 to week 52.
Gastrointestinal disorders Diarrhoea	5.1% 9/177 • Number of events 10 • Adverse events were collected from week 0 to week 52.	4.1% 7/170 • Number of events 7 • Adverse events were collected from week 0 to week 52.
Nervous system disorders Headache	14.7% 26/177 • Number of events 65 • Adverse events were collected from week 0 to week 52.	13.5% 23/170 • Number of events 44 • Adverse events were collected from week 0 to week 52.

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Insulin Detemir n=177 participants at risk Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals	NPH Insulin n=170 participants at risk Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals
Metabolism and nutrition disorders Diabetic Ketoacidosis	1.7% 3/177 • Number of events 3 • Adverse events were collected from week 0 to week 52.	2.4% 4/170 • Number of events 4 • Adverse events were collected from week 0 to week 52.
Metabolism and nutrition disorders Hypoglycaemia	0.56% 1/177 • Number of events 1 • Adverse events were collected from week 0 to week 52.	1.8% 3/170 • Number of events 3 • Adverse events were collected from week 0 to week 52.
Metabolism and nutrition disorders Diabetes Mellitus Inadequate Control	0.56% 1/177 • Number of events 1 • Adverse events were collected from week 0 to week 52.	0.59% 1/170 • Number of events 1 • Adverse events were collected from week 0 to week 52.
Metabolism and nutrition disorders Hypoglycaemic Unconsciousness	0.00% 0/177 • Adverse events were collected from week 0 to week 52.	1.2% 2/170 • Number of events 3 • Adverse events were collected from week 0 to week 52.
Infections and infestations Gastroenteritis	2.3% 4/177 • Number of events 4 • Adverse events were collected from week 0 to week 52.	1.2% 2/170 • Number of events 2 • Adverse events were collected from week 0 to week 52.
Infections and infestations Viral Infection	0.56% 1/177 • Number of events 1 • Adverse events were collected from week 0 to week 52.	0.59% 1/170 • Number of events 1 • Adverse events were collected from week 0 to week 52.
Infections and infestations Gastroenteritis Shigella	0.56% 1/177 • Number of events 1 • Adverse events were collected from week 0 to week 52.	0.00% 0/170 • Adverse events were collected from week 0 to week 52.
Infections and infestations Gastroenteritis Viral	0.00% 0/177 • Adverse events were collected from week 0 to week 52.	0.59% 1/170 • Number of events 1 • Adverse events were collected from week 0 to week 52.
Infections and infestations Laryngitis	0.00% 0/177 • Adverse events were collected from week 0 to week 52.	0.59% 1/170 • Number of events 1 • Adverse events were collected from week 0 to week 52.
Infections and infestations Otitis Media Acute	0.56% 1/177 • Number of events 1 • Adverse events were collected from week 0 to week 52.	0.00% 0/170 • Adverse events were collected from week 0 to week 52.
Infections and infestations Soft Tissue Infection	0.56% 1/177 • Number of events 1 • Adverse events were collected from week 0 to week 52.	0.00% 0/170 • Adverse events were collected from week 0 to week 52.
Gastrointestinal disorders Dyspepsia	0.56% 1/177 • Number of events 1 • Adverse events were collected from week 0 to week 52.	0.59% 1/170 • Number of events 1 • Adverse events were collected from week 0 to week 52.
Gastrointestinal disorders Gastritis	0.00% 0/177 • Adverse events were collected from week 0 to week 52.	1.2% 2/170 • Number of events 2 • Adverse events were collected from week 0 to week 52.
Gastrointestinal disorders Abdominal Pain	0.56% 1/177 • Number of events 1 • Adverse events were collected from week 0 to week 52.	0.00% 0/170 • Adverse events were collected from week 0 to week 52.
Injury, poisoning and procedural complications Burns Second Degree	0.56% 1/177 • Number of events 1 • Adverse events were collected from week 0 to week 52.	0.00% 0/170 • Adverse events were collected from week 0 to week 52.
Injury, poisoning and procedural complications Medication Error	0.00% 0/177 • Adverse events were collected from week 0 to week 52.	0.59% 1/170 • Number of events 1 • Adverse events were collected from week 0 to week 52.
Nervous system disorders Convulsion	0.00% 0/177 • Adverse events were collected from week 0 to week 52.	0.59% 1/170 • Number of events 1 • Adverse events were collected from week 0 to week 52.
Nervous system disorders Epilepsy	0.00% 0/177 • Adverse events were collected from week 0 to week 52.	0.59% 1/170 • Number of events 1 • Adverse events were collected from week 0 to week 52.
Renal and urinary disorders Nephropathy	0.00% 0/177 • Adverse events were collected from week 0 to week 52.	0.59% 1/170 • Number of events 1 • Adverse events were collected from week 0 to week 52.
Respiratory, thoracic and mediastinal disorders Adenoidal Hypertrophy	0.00% 0/177 • Adverse events were collected from week 0 to week 52.	0.59% 1/170 • Number of events 1 • Adverse events were collected from week 0 to week 52.