Comparison of the Efficacy and Safety of Two Different Do... | NCT01680341

NCT01680341

ID	Type	Description	Link
2012-000373-23	EudraCT Number
U1111-1127-4114	Other Identifier	WHO

Status Module

Oversight Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
IDegAsp Simple	Experimental		Drug: insulin degludec/insulin aspart
IDegAsp Step wise	Experimental		Drug: insulin degludec/insulin aspart

Interventions

Name	Type	Description	Arm Group Labels	Other Names
insulin degludec/insulin aspart	Drug	Twice weekly self-titration at intervals of 3-4 days, based upon a single pre-breakfast and pre-dinner SMPG (self-measured plasma glucose) value. For subcutaneous (s.c., under the skin) administration.

Outcomes Module

Measure	Description	Time Frame
Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%)	Change from baseline in HbA1c after 26 weeks of treatment.	Week 0, Week 26

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG)	Change from baseline in fasting plasma glucose (FPG) after 26 weeks of treatment	Week 0, Week 26
Subjects With HbA1c Below 7.0%	Number of subjects with HbA1c below 7% after 26 weeks of treatment.

Eligibility 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		Goodyear	Arizona	85395	United States
Novo Nordisk Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
23710902	Result	Bode BW, Buse JB, Fisher M, Garg SK, Marre M, Merker L, Renard E, Russell-Jones DL, Hansen CT, Rana A, Heller SR; BEGIN(R) Basal-Bolus Type 1 trial investigators. Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN((R)) Basal-Bolus Type 1): 2-year results of a randomized clinical trial. Diabet Med. 2013 Nov;30(11):1293-7. doi: 10.1111/dme.12243. Epub 2013 Jun 17.
29451706

Label	URL
Clinical Trials at Novo Nordisk	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	IDegAsp Simple	Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	IDegAsp Simple	Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.
BG001	IDegAsp Step Wise	IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).
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
	BG00058.8± 9.8 BG00159.1± 9.4 BG00258.9± 9.6

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00060 BG00153 BG002

Glycosylated Haemoglobin (HbA1c)

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0008.2± 0.9 BG0018.2± 0.9 BG002

Fasting plasma glucose

Mean

Standard Deviation

mmol/L

Title

Denominators

Categories

Title	Measurements
	BG0007.8± 2.3 BG0018.1± 3.0 BG002

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 From Baseline in HbA1c (Glycosylated Haemoglobin) (%)

Change from baseline in HbA1c after 26 weeks of treatment.

The full analysis set (FAS) included all randomised subjects. Missing data were imputed using last observation carried forward (LOCF).

Posted

Least Squares Mean

Standard Error

Percent (%) glycosylated haemoglobin

Week 0, Week 26

ID	Title	Description
OG000	IDegAsp Simple	Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.
OG001	IDegAsp Step Wise	IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).

Units	Counts
Participants	OG000136 OG001136

Title

Denominators

Categories

Title	Measurements
	OG000-1.45± 0.09 OG001-1.33± 0.09

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG)

Change from baseline in fasting plasma glucose (FPG) after 26 weeks of treatment

The full analysis set (FAS) included all randomised subjects. Missing data were imputed using LOCF.

Posted

Least Squares Mean

Standard Error

mmol/L

Week 0, Week 26

ID	Title	Description
OG000	IDegAsp Simple	Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.
OG001	IDegAsp Step Wise	IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).

Secondary

Subjects With HbA1c Below 7.0%

Number of subjects with HbA1c below 7% after 26 weeks of treatment.

The full analysis set (FAS) included all randomised subjects. Missing data were imputed using LOCF.

Posted

Number

Subjects

Week 26

ID	Title	Description
OG000	IDegAsp Simple	Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.
OG001	IDegAsp Step Wise	IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).

Secondary

Percentage of Subjects With HbA1c Below 7.0% Without Confirmed Hypoglycaemia

Percentage of subjects with HbA1c below 7% without confirmed hypoglycaemic episodes after 26 weeks of treatment.

The full analysis set (FAS) included all randomised subjects. Missing data were imputed using LOCF. Twenty five (25) subjects did not contribute to statistical analysis as Endpoint was only defined for subjects exposed for at least 12 treatment weeks.

Posted

Number

percentage of subjects

Week 26

ID	Title	Description
OG000	IDegAsp Simple	Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.
OG001	IDegAsp Step Wise	IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).

Secondary

Incidence of Treatment Emergent Adverse Events (TEAEs)

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

The safety analysis set included all subjects who received at least one dose of the investigational product.

Posted

Number

number of events

Weeks 0-28

ID	Title	Description
OG000	IDegAsp Simple	Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.
OG001	IDegAsp Step Wise	IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).

Secondary

Number of Treatment Emergent Confirmed Hypoglycaemic Episodes

Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

The safety analysis set included all subjects who received at least one dose of the investigational product.

Posted

Number

episodes

Weeks 0-27

ID	Title	Description
OG000	IDegAsp Simple	Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.
OG001	IDegAsp Step Wise	IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).

Secondary

Number of Treatment Emergent Confirmed Hypoglycaemic Episodes in the Maintenance Period

Confirmed hypoglycaemic episodes in the maintenance period (from Week 16 to the end of the trial including follow-up [Week 27]) consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

The safety analysis set included all subjects who received at least one dose of the investigational product. Subjects in maintenance period were included in this analysis.

Posted

Number

episodes

From week 16 to end of trial including follow-up (week 27)

ID	Title	Description
OG000	IDegAsp Simple	Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.
OG001	IDegAsp Step Wise	IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).

Secondary

Number of Treatment Emergent Nocturnal (00:01-05:59) Confirmed Hypoglycaemic Episodes

The safety analysis set included all subjects who received at least one dose of the investigational product.

Posted

Number

episodes

Weeks 0-27

ID	Title	Description
OG000	IDegAsp Simple	Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.
OG001	IDegAsp Step Wise	IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).

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	IDegAsp Simple	Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.			7	135	45	135
EG001	IDegAsp Step Wise	IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).			10	134	53	134

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected134 at risk
Aortic valve stenosis	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected134 at risk
Coronary artery disease	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected135 at risk EG0011 events1 affected134 at risk
Coronary artery occlusion	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected134 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected134 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected134 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected134 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected134 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected134 at risk
Abscess limb	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected134 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0002 events2 affected135 at risk EG0010 events0 affected134 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected134 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected134 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected134 at risk
Pulmonary arterial hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected134 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected134 at risk
Hypertension	Vascular disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected134 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0007 events5 affected135 at risk EG00112 events8 affected134 at risk
Bronchitis	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0006 events6 affected135 at risk EG0017 events7 affected134 at risk
Influenza	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0005 events5 affected135 at risk EG00112 events12 affected134 at risk
Nasopharyngitis	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG00016 events12 affected135 at risk EG00123 events20 affected134 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG00016 events14 affected135 at risk EG00112 events10 affected134 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG0006 events6 affected135 at risk EG0019 events8 affected134 at risk
Headache	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG00010 events9 affected135 at risk EG0018 events8 affected134 at risk

ID	Term
D003920	Diabetes Mellitus
D003924	Diabetes Mellitus, Type 2

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