A Trial Investigating the Efficacy and Safety of Insulin... | NCT02131272

NCT02131272

ID	Type	Description
2013-005500-33	EudraCT Number
U1111-1151-4056	Other Identifier	WHO
2015-1316	Registry Identifier	REec

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Insulin detemir and diet/exercise	Experimental	Current OADs i.e. metformin or other OADs are continued unchanged	Drug: Insulin NPH Behavioral: Diet/exercise
Insulin NPH and diet/exercise	Active Comparator	Current OADs i.e. metformin or other OADs are continued unchanged	Drug: Insulin detemir Behavioral: Diet/exercise

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Insulin detemir	Drug	Administered subcutaneously (s.c., under the skin) once or twice daily. The subjects' pre-trial OAD's i.e. metformin treatment should continue unchanged during the treatment period.

Outcomes Module

Measure	Description	Time Frame
Change in HbA1c (Glycosylated Haemoglobin)	Estimated mean change in HbA1c (glycosylated haemoglobin) from baseline to week 26.	week 0, week 26

Secondary Outcomes

Measure	Description	Time Frame
Change in Body Weight Standard Deviation Score (SDS)	Change in body weight standard deviation score (SDS) from baseline to week 26. In order to reduce the variability in body weight measurements, SDS were calculated. SDS for weight was derived by comparing the actual measurements with standard growth charts for the United States. Standard values provided by the standard growth charts according to the subject's sex and age at the time of the measurement were used to calculate the SDS.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Global Clinical Registry (GCR, 1452)	Novo Nordisk A/S	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novo Nordisk Investigational Site		Tucson	Arizona	85724	United States
Novo Nordisk Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30014302	Result	Wheeler MD, Barrientos-Perez M, Lo FS, Liang B, Lunsford A, Thorisdottir O, Zuckerman-Levin N. A 26-week, randomized trial of insulin detemir versus NPH insulin in children and adolescents with type 2 diabetes (iDEAt2). Eur J Pediatr. 2018 Oct;177(10):1497-1503. doi: 10.1007/s00431-018-3205-z. Epub 2018 Jul 16.

Label	URL
Clinical Trials at Novo Nordisk	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Insulin Detemir + Metformin + Diet/Exercise	Subjects were treated with insulin detemir 100 U/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin detemir was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin detemir unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Insulin NPH and diet/exercise

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Insulin Detemir + Metformin + Diet/Exercise	Subjects were treated with insulin detemir 100 U/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin detemir was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin detemir unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.
BG001	Insulin NPH + Metformin + Diet/Exercise	Subjects were treated with NPH 100 IU/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin NPH was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin NPH unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00015.0± 2.1 BG00115.0± 2.2 BG00215.0± 2.1

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00012 BG00115 BG002

Glycosylated haemoglobin (HbA1c)

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0008.72± 0.86 BG0018.95± 1.05 BG002

Body weight standard deviation score

In order to reduce the variability in body weight measurements, standard deviation scores (SDS) were calculated. SDS for weight was derived by comparing the actual measurements with standard growth charts for the United States. Standard values provided by the standard growth charts according to the subject's sex and age at the time of the measurement were used to calculate the SDS.

Mean

Standard Deviation

standard deviation score

Title

Denominators

Categories

Title	Measurements
	BG0001.532± 0.685 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in HbA1c (Glycosylated Haemoglobin)

Estimated mean change in HbA1c (glycosylated haemoglobin) from baseline to week 26.

Full analysis set included all the randomised subjects.

Posted

Least Squares Mean

Standard Error

Percentage of glycosylated haemoglobin

week 0, week 26

ID	Title	Description
OG000	Insulin Detemir + Metformin + Diet/Exercise	Subjects were treated with insulin detemir 100 U/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin detemir was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin detemir unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.
OG001	Insulin NPH + Metformin + Diet/Exercise	Subjects were treated with NPH 100 IU/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin NPH was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin NPH unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.

Units	Counts
Participants	OG00020 OG00122

Title

Denominators

Categories

Title	Measurements
	OG000-0.64± 0.32 OG001-0.81± 0.31

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	HbA1c measurements were analysed with a mixed model for repeated measurements with an unstructured covariance matrix. The model included treatment, visit, age group, prior antidiabetic therapy and interaction between prior antidiabetic therapy and age group as fixed factors and the HbA1c baseline value as covariate. Interactions between visit and all factors and covariates were also included in the model.	Mixed Models Analysis		0.3075	p value is reported for 1 sided test	Least squares mean difference	0.17			2-Sided	95	-0.74	1.09					Non-Inferiority or Equivalence

Secondary

Change in Body Weight Standard Deviation Score (SDS)

Change in body weight standard deviation score (SDS) from baseline to week 26. In order to reduce the variability in body weight measurements, SDS were calculated. SDS for weight was derived by comparing the actual measurements with standard growth charts for the United States. Standard values provided by the standard growth charts according to the subject's sex and age at the time of the measurement were used to calculate the SDS.

Full analysis set included all the randomised subjects.

Posted

Mean

Standard Deviation

standard deviation score

week 0, week 26

ID	Title	Description
OG000	Insulin Detemir + Metformin + Diet/Exercise	Subjects were treated with insulin detemir 100 U/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin detemir was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin detemir unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.
OG001	Insulin NPH + Metformin + Diet/Exercise

Secondary

Proportion of Subjects Achieving HbA1c Below 7.0%, Who Have Not Experienced Any Treatment Emergent Severe Hypoglycaemic Episodes Within the Last 14 Weeks of Treatment.

Proportion of subjects achieving HbA1c <7.0% is presented as percentage of subjects achieving HbA1c <7.0%, who have not experienced any treatment emergent severe hypoglycaemic episodes (an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) within the last 14 weeks of treatment.

Full analysis set included all the randomised subjects. Only subjects who have been exposed for a minimum of 14 weeks contributed to the analysis (20 subjects in the Insulin detemir + metformin + diet/exercise arm and 21 subjects in the Insulin NPH + metformin + diet/exercise arm).

Posted

Number

Percentage of subjects

At week 26

ID	Title	Description
OG000	Insulin Detemir + Metformin + Diet/Exercise	Subjects were treated with insulin detemir 100 U/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin detemir was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin detemir unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.

Secondary

Proportion of Subjects Achieving HbA1c Below 7.5%, Who Have Not Experienced Any Treatment Emergent Severe Hypoglycaemic Episodes Within the Last 14 Weeks of Treatment

Proportion of subjects achieving HbA1c below 7.5% is presented as percentage of subjects achieving HbA1c <7.5%, who have not experienced any treatment emergent severe hypoglycaemic episodes (an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) within the last 14 weeks of treatment.

Posted

Number

Percentage of subjects

At week 26

ID	Title	Description
OG000	Insulin Detemir + Metformin + Diet/Exercise	Subjects were treated with insulin detemir 100 U/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin detemir was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin detemir unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.

Secondary

Total Number of Treatment Emergent Nocturnal (23:00-06:59) Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes

The total number of blood glucose confirmed symptomatic nocturnal (time of onset between 23:00 and 06.59 both inclusive) severe (an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or blood glucose confirmed symptomatic hypoglycaemic episodes (plasma glucose value <3.1 mmol/L [56 mg/dL] with symptoms consistent with hypoglycaemia) experienced by the subjects during the trial.

Safety analysis set included all subjects receiving at least one dose of randomised treatment.

Posted

Number

Number of episodes

Weeks 0 - 26

ID	Title	Description
OG000	Insulin Detemir + Metformin + Diet/Exercise	Subjects were treated with insulin detemir 100 U/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin detemir was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin detemir unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.
OG001	Insulin NPH + Metformin + Diet/Exercise

Secondary

Total Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes

Total number of treatment emergent severe (an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or blood glucose confirmed symptomatic hypoglycaemic episodes (plasma glucose value <3.1 mmol/L [56 mg/dL] with symptoms consistent with hypoglycaemia) experienced by the subjects during the trial.

Safety analysis set included all subjects receiving at least one dose of randomised treatment.

Posted

Number

Number of episodes

Weeks 0 - 26

ID	Title	Description
OG000	Insulin Detemir + Metformin + Diet/Exercise	Subjects were treated with insulin detemir 100 U/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin detemir was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin detemir unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.
OG001	Insulin NPH + Metformin + Diet/Exercise

Secondary

Incidence of Adverse Events (AEs)

The total number of treatment emergent adverse events (the onset of the adverse event is on or after the first day of trial product administration, and no later than 7 days after the last day of trial product administration) reported during the 26 weeks of treatment.

Safety analysis set included all subjects receiving at least one dose of randomised treatment.

Posted

Number

Number of events

weeks 0 - 26

ID	Title	Description
OG000	Insulin Detemir + Metformin + Diet/Exercise	Subjects were treated with insulin detemir 100 U/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin detemir was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin detemir unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.
OG001	Insulin NPH + Metformin + Diet/Exercise	Subjects were treated with NPH 100 IU/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin NPH was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin NPH unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Insulin Detemir + Metformin + Diet/Exercise	Subjects were treated with insulin detemir 100 U/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin detemir was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin detemir unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.			0	20	8	20
EG001	Insulin NPH + Metformin + Diet/Exercise	Subjects were treated with NPH 100 IU/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin NPH was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin NPH unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.			1	22	9	22

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Migraine	Nervous system disorders	MedDRA	Systematic Assessment		EG0000 events0 affected20 at risk EG0011 events1 affected22 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected22 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected22 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected22 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected22 at risk
Gastroenteritis viral	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected22 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0004 events3 affected20 at risk EG0014 events1 affected22 at risk
Impetigo	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected22 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected20 at risk EG0013 events2 affected22 at risk
Injection site erythema	General disorders	MedDRA	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected22 at risk
Lip dry	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected22 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected22 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected20 at risk EG0013 events3 affected22 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0004 events1 affected20 at risk EG0010 events0 affected22 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected22 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected22 at risk
Soft tissue injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected22 at risk
Toothache	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected22 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events1 affected22 at risk
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected22 at risk
Viral infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected22 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 events2 affected20 at risk EG0010 events0 affected22 at risk

The trial was terminated earlier than planned due to a very slow recruitment rate. Based on the low number of subjects, the conclusions should be interpreted with caution.

Certain Agreements

ID	Term
D003920	Diabetes Mellitus
D003924	Diabetes Mellitus, Type 2

ID	Term
D000069057	Insulin Detemir
D007336	Insulin, Isophane

Ancestor Terms

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

Subjects were treated with NPH 100 IU/mL administered subcutaneously in the thigh region once or twice daily for a period of 26 weeks. For insulin naïve subjects, insulin NPH was initiated at a dose of 0.1-0.2 U/kg with a maximum dose of 10 U at the investigators discretion. Subjects who were already on basal insulin were switched to insulin NPH unit-to-unit once or twice daily, depending on previous injection frequency. Subjects were dosed according to individual requirements during the trial period. All subjects continued treatment with metformin on their pre-study dose(s) throughout the trial. The diet/exercise intervention was performed through changes in eating and activity behaviours.

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases