A Trial Investigating the Efficacy and Safety of Insulin Degludec/Insulin Aspart Once Daily Plus Insulin Aspart for the Remaining Meals Versus Insulin Detemir Once or Twice Daily Plus Meal Time Insulin Aspart in Children and Adolescents With Type 1 Diabetes Mellitus

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01835431

Enrollment

362

Registered

2013-04-19

Start date

2013-10-17

Completion date

2014-11-07

Last updated

2019-06-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes, Diabetes Mellitus, Type 1

Brief summary

This trial is conducted in Asia, Europe and North and South America. The aim of the trial is to investigate the efficacy and safety of insulin degludec/insulin aspart once daily plus insulin aspart for the remaining meals in children and adolescents with type 1 diabetes mellitus.

Interventions

DRUGinsulin degludec/insulin aspart

Administered subcutaneously (s.c., under the skin) once daily with a main meal. Dose individually adjusted.

DRUGinsulin aspart

Administered s.c. with the remaining meals. Dose individually adjusted.

DRUGinsulin detemir

Administered s.c. once or twice daily. Dose individually adjusted. Subjects will continue with their pre-trial dosing scheme (once (OD) or twice daily (BID)) and will be allowed to switch from OD to BID dosing.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

1 Years to 17 Years

Healthy volunteers

Inclusion criteria

- Informed consent obtained before any trial related activities. Trial related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Subjects diagnosed with type 1 diabetes mellitus - HbA1c below or equal to 11.0%

Exclusion criteria

- Known hypoglycaemic unawareness or recurrent severe hypoglycaemic events as judged by the investigator - More than 1 episode of diabetic ketoacidosis requiring hospitalisation within the last 3 months prior to Visit 1 (Screening) - Any chronic disorder or significant concomitant disease, which in the investigator's opinion might jeopardise the subject's safety or compliance with the protocol

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%)	Week 0 to week 16	Percentage point change in glycosylated haemoglobin A1c (HbA1c) from baseline (week 0) to 16 Weeks. Change from baseline summary statistics at week 16 contains only those who had both baseline and week 16 assesment.

Secondary

Measure	Time frame	Description
Incidence of Treatment Emergent Adverse Events (TEAEs)	After 16 weeks of treatment	A Treatment Emergent Adverse Event (TEAE) was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day on randomised treatment.
Number of Treatment Emergent Confirmed Hypoglycaemic Episodes (Plasma Glucose (PG) Below 3.1mmol/L (56mg/dL) or Severe Hypoglycaemia)	After 16 weeks of treatment	Treatment emergent hypoglycaemic episodes (PG \< 3.1 mmol/L (56 mg/dL) or severe hypoglycaemia). Confirmed hypoglycaemic episodes were defined as episodes that were either: 1. Severe (i.e. the child is having altered mental status and cannot assist in their care, is semiconscious or unconscious or in coma with or without convulsions and may require parenteral therapy (glucagon or i.v. glucose), or 2. An episode biochemically confirmed by PG value of \<3.1 mmol/L (56 mg/dL), with or without symptoms consistent with hypoglycaemia.
Change From Baseline in Fasting Plasma Glucose	week 0, week 16	Change from baseline in FPG after 16 weeks of treatment. Change from baseline summary statistics at week 16 contains only those who had both baseline and week 16 assesment.
Number of Hyperglycaemic Episodes (PG Above 14.0 mmol/L (250 mg/dL) Where Subject Looks/Feels Ill	After 16 weeks of treatment	The episode of hyperglycaemia was noted when the glucose measurement was 14.0mmol/L or above and the subject looked /felt ill.
Number of Hyperglycaemic Episodes (PG Above 14.0 mmol/L (250 mg/dL) Where Subject Looks/Feels Ill With Ketosis (Blood Ketones Above 1.5 mmol/L)	After 16 weeks of treatment	The episode of hyperglycaemia was noted when the glucose measurement was 14.0mmol/L or above and the subject looked /felt ill. The ketone meaurement involved an additional finger prick and ketosis was considered present if blood ketones were higher than 1.5mmol/L
Number of Treatment Emergent Nocturnal Confirmed Hypoglycaemic Episodes	After 16 weeks of treatment	The confirmed hypoglycaemic episodes occurring between 23:00 and 07:00 were considered for this endpoint

Countries

Belgium, Brazil, Canada, Croatia, Czechia, India, Israel, North Macedonia, Poland, Russia, Serbia, Slovenia, South Africa, Spain, United States

Participant flow

Recruitment details

The trial was conducted at 63 sites in 14 countries as follows: Belgium: 3 sites; Brazil: 1 sites; Canada: 3 sites; Czech Republic 3 sites; Croatia: 2 sites; Israel: 6 sites; Macedonia: 2 sites; Poland: 3 sites; Russia: 5 sites; Serbia: 4 sites; Slovenia: 1 sites; South Africa: 2 sites; Spain: 5 sites; and United States: 23 sites.

Participants by arm

Arm	Count
IDegAsp OD Insulin degludec/insulin aspart (IDegAsp) once daily (OD) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 1-3 times daily for 16 weeks.	182
IDet OD/BID Insulin detemir (IDet) OD/BID (once daily /twice daily) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 2-4 times daily for 16 weeks	180
Total	362

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0
Overall Study	other	0	2
Overall Study	Protocol Violation	1	0
Overall Study	Withdrawal by Subject	6	10

Baseline characteristics

Characteristic	IDegAsp OD	IDet OD/BID	Total
Age, Continuous	10.5 years STANDARD_DEVIATION 4.3	10.8 years STANDARD_DEVIATION 4.6	10.6 years STANDARD_DEVIATION 4.5
Fasting plasma Glucose (FPG)	8.6 mmol/L STANDARD_DEVIATION 4.4	8.1 mmol/L STANDARD_DEVIATION 4.2	8.4 mmol/L STANDARD_DEVIATION 4.3
HbA1c	8.1 percentage (%) STANDARD_DEVIATION 1.2	8.1 percentage (%) STANDARD_DEVIATION 1.2	8.1 percentage (%) STANDARD_DEVIATION 1.2
Sex: Female, Male Female	93 Participants	94 Participants	187 Participants
Sex: Female, Male Male	89 Participants	86 Participants	175 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	96 / 181	97 / 179
serious Total, serious adverse events	11 / 181	7 / 179

Outcome results

Primary

Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%)

Percentage point change in glycosylated haemoglobin A1c (HbA1c) from baseline (week 0) to 16 Weeks. Change from baseline summary statistics at week 16 contains only those who had both baseline and week 16 assesment.

Time frame: Week 0 to week 16

Population: The FAS included all randomised subjects. 20 subjects were withdrawn and only 4 subjects though completed the study did not have assesments.

Arm	Measure	Value (MEAN)	Dispersion
IDegAsp OD	Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%)	-0.3 percentage (%)	Standard Deviation 1
IDet OD/BID	Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%)	-0.3 percentage (%)	Standard Deviation 0.9

Secondary

Change From Baseline in Fasting Plasma Glucose

Change from baseline in FPG after 16 weeks of treatment. Change from baseline summary statistics at week 16 contains only those who had both baseline and week 16 assesment.

Time frame: week 0, week 16

Population: The FAS included all randomised subjects. 338 subjects had assessment at baseline, 326 had assessment at week 16, 2 subjects were withdrawn before exposure and 22 subjects week 16 assessment was not done.

Arm	Measure	Value (MEAN)	Dispersion
IDegAsp OD	Change From Baseline in Fasting Plasma Glucose	-0.3 mmol/L	Standard Deviation 6.4
IDet OD/BID	Change From Baseline in Fasting Plasma Glucose	-0.1 mmol/L	Standard Deviation 4.8

Secondary

Incidence of Treatment Emergent Adverse Events (TEAEs)

A Treatment Emergent Adverse Event (TEAE) was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day on randomised treatment.