Comparison of the Efficacy and Safety of Two Intensificat... | NCT01388361

NCT01388361

ID	Type	Description	Link
2011-001493-25	EudraCT Number
U1111-1120-2782	Other Identifier	WHO

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
IDeg (non-randomised)	Experimental	Drug: insulin degludec
IDeg + IAsp	Experimental	Drug: insulin degludec Drug: insulin aspart
IDeg + liraglutide	Experimental	Drug: insulin degludec Drug: liraglutide

Interventions

Name	Type	Description	Arm Group Labels	Other Names
insulin degludec	Drug	Injected s.c. (under the skin) once daily. The doses will be individually adjusted	IDeg (non-randomised) IDeg + IAsp IDeg + liraglutide

Outcomes Module

Measure	Description	Time Frame
Change From Baseline in HbA1c (%) (Glycosylated Haemoglobin)	Values for change in HbA1c from baseline to 26 weeks of treatment period.	week 0, week 26

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG)	Values for change in FPG in mmol/L from baseline to week 26 of randomised period.	week 0, week 26
Change From Baseline in Body Weight	Corresponds to the values of change in body weight in kilograms from baseline to week 26.

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		Concord	California	94520-1926	United States
Novo Nordisk Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
24443830	Result	Mathieu C, Rodbard HW, Cariou B, Handelsman Y, Philis-Tsimikas A, Ocampo Francisco AM, Rana A, Zinman B; BEGIN: VICTOZA ADD-ON (NN1250-3948) study group. A comparison of adding liraglutide versus a single daily dose of insulin aspart to insulin degludec in subjects with type 2 diabetes (BEGIN: VICTOZA ADD-ON). Diabetes Obes Metab. 2014 Jul;16(7):636-44. doi: 10.1111/dom.12262. Epub 2014 Feb 11.

Label	URL
Clinical Trials at Novo Nordisk	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	IDeg	This non-randomised arm consisted of subjects treated with IDeg + metformin who achieved the target glycosylated haemoglobin (HbA1c) < 7.0 % at the end of treatment in NN1250-3643. Subjects were treated with once-daily subcutaneous administration of IDeg 100 U/mL prefilled pen along with stable and pre-trial dose of oral antidiabetic drug metformin for 26-weeks. These subjects continued on IDeg + metformin to assess the treatment regimen's ability to sustain long term glycaemic control. No comparisons of endpoints were made between the non-randomised and randomised treatment arms.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

The full analysis set (FAS) included all randomised patients except for 7 subjects (2 subjects with IDeg+ liraglutide; 5 subjects with IDeg+IAsp arm) fasting plasma glucose (FPG) values were missing at baseline. Non-randomised set (NAS) included all non-randomised subjects, the FPG values were missing for 10 subjects at baseline.

Arm/Group Information

ID	Title	Description
BG000	IDeg	This non-randomised arm consisted of subjects treated with IDeg + metformin who achieved the target glycosylated haemoglobin (HbA1c) < 7.0 % at the end of treatment in NN1250-3643. Subjects were treated with once-daily subcutaneous administration of IDeg 100 U/mL prefilled pen along with stable and pre-trial dose of oral antidiabetic drug metformin for 26-weeks. These subjects continued on IDeg + metformin to assess the treatment regimen's ability to sustain long term glycaemic control. No comparisons of endpoints were made between the non-randomised and randomised treatment arms.
BG001	IDeg + Liraglutide	All subjects in this arm were randomised to once-daily subcutaneous administration of IDeg 100 U/mL in a prefilled pen along with once-daily subcutaneous administration of liraglutide (6 mg/mL) in a prefilled pen for 26 weeks of treatment. Subjects continued their oral antidiabetic drug metformin at a stable, pre-trial dose throughout the trial period.
BG002	IDeg + IAsp OD	Subjects in this arm were randomised to once-daily subcutaneous administration of IDeg 100 U/mL in prefilled pen along with once-daily subcutaneous administration of insulin aspart (IAsp)100 U/mL in a FlexPen® administered just before the largest meal for 26 weeks of treatment. Subjects continued their oral antidiabetic drug metformin at a stable, pre-trial dose throughout the trial period.
BG003	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

Non-randomised population.

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00061.9± 9.3 BG001NA± NAValues available in the next row, baseline values for IDeg + Liraglutide vs. IDeg + IAsp OD. BG002NA± NAValues available in the next row, baseline values for IDeg + Liraglutide vs. IDeg + IAsp OD.

Age, Continuous

Randomised population.

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG000NA± NAValues available in the previous row, baseline values for non-randomised arm IDeg. BG00161.1± 9.5

Sex: Female, Male

Non-randomised population.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00090 BG001NAValues available in the next row, baseline values for IDeg + Liraglutide vs. IDeg + IAsp OD.

Sex: Female, Male

Randomised population.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000NAValues available in the previous row, baseline values for non-randomised arm IDeg. BG00125

Glycosylated haemoglobin (HbA1c)

Non-randomised population.

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0006.4± 0.4 BG001NA± NAValues available in the next row, baseline values for IDeg + Liraglutide vs. IDeg + IAsp OD.

Glycosylated haemoglobin (HbA1c)

Randomised population.

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Title

Denominators

Categories

Title	Measurements
	BG000NA± NAValues available in the previous row, baseline values for non-randomised arm IDeg. BG001

Fasting plasma glucose (FPG)

Non-randomised population.

Mean

Standard Deviation

mmol/L

Title

Denominators

Categories

Title	Measurements
	BG0006.7± 1.8 BG001NA± NAValues available in the next row, baseline values for IDeg + Liraglutide vs. IDeg + IAsp OD.

Fasting plasma glucose (FPG)

Randomised population.

Mean

Standard Deviation

mmol/L

Title

Denominators

Categories

Title	Measurements
	BG000NA± NAValues available in the previous row, baseline values for non-randomised arm IDeg. BG0016.4± 2.4

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)

Values for change in HbA1c from baseline to 26 weeks of treatment period.

The FAS and NAS included all randomised and non-randomised subjects respectively, and missing data was imputed using last observation carried forward (LOCF).

Posted

Mean

Standard Deviation

percentage of glycosylated haemoglobin

week 0, week 26

ID	Title	Description
OG000	IDeg	This non-randomised arm consisted of subjects treated with IDeg + metformin who achieved the target glycosylated haemoglobin (HbA1c) < 7.0 % at the end of treatment in NN1250-3643. Subjects were treated with once-daily subcutaneous administration of IDeg 100 U/mL prefilled pen along with stable and pre-trial dose of oral antidiabetic drug metformin for 26-weeks. These subjects continued on IDeg + metformin to assess the treatment regimen's ability to sustain long term glycaemic control. No comparisons of endpoints were made between the non-randomised and randomised treatment arms.
OG001	IDeg + Liraglutide	All subjects in this arm were randomised to once-daily subcutaneous administration of IDeg 100 U/mL in a prefilled pen along with once-daily subcutaneous administration of liraglutide (6 mg/mL) in a prefilled pen for 26 weeks of treatment. Subjects continued their oral antidiabetic drug metformin at a stable, pre-trial dose throughout the trial period.
OG002	IDeg + IAsp OD	Subjects in this arm were randomised to once-daily subcutaneous administration of IDeg 100 U/mL in prefilled pen along with once-daily subcutaneous administration of insulin aspart (IAsp)100 U/mL in a FlexPen® administered just before the largest meal for 26 weeks of treatment. Subjects continued their oral antidiabetic drug metformin at a stable, pre-trial dose throughout the trial period.

Units	Counts
Participants	OG000236 OG00188 OG00289

Title

Denominators

Categories

Title	Measurements
	OG0000.10± 0.40 OG001-0.74± 0.73 OG002-0.39± 0.72

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG)

Values for change in FPG in mmol/L from baseline to week 26 of randomised period.

Both sets of FAS and NAS included all randomised and non-randomised subjects in the treatment period. The FPG values were missing for 7 subjects in FAS (2 subjects with IDeg+ liraglutide; 5 subjects with IDeg+IAsp arm) and 10 subjects in NAS for IDeg arm at baseline. The missing data was imputed using LOCF.

Posted

Mean

Standard Deviation

mmol/L

week 0, week 26

ID	Title	Description
OG000	IDeg	This non-randomised arm consisted of subjects treated with IDeg + metformin who achieved the target glycosylated haemoglobin (HbA1c) < 7.0 % at the end of treatment in NN1250-3643. Subjects were treated with once-daily subcutaneous administration of IDeg 100 U/mL prefilled pen along with stable and pre-trial dose of oral antidiabetic drug metformin for 26-weeks. These subjects continued on IDeg + metformin to assess the treatment regimen's ability to sustain long term glycaemic control. No comparisons of endpoints were made between the non-randomised and randomised treatment arms.
OG001	IDeg + Liraglutide	All subjects in this arm were randomised to once-daily subcutaneous administration of IDeg 100 U/mL in a prefilled pen along with once-daily subcutaneous administration of liraglutide (6 mg/mL) in a prefilled pen for 26 weeks of treatment. Subjects continued their oral antidiabetic drug metformin at a stable, pre-trial dose throughout the trial period.

Secondary

Change From Baseline in Body Weight

Corresponds to the values of change in body weight in kilograms from baseline to week 26.

Both sets of FAS and NAS included all randomised and non-randomised subjects in the treatment period and missing data was imputed using LOCF. At baseline, the body weight values were missing for 1 subject in IDeg + Liraglutide arm from FAS and 3 subjects in NAS for IDeg arm.

Posted

Mean

Standard Deviation

week 0, week 26

ID	Title	Description
OG000	IDeg	This non-randomised arm consisted of subjects treated with IDeg + metformin who achieved the target glycosylated haemoglobin (HbA1c) < 7.0 % at the end of treatment in NN1250-3643. Subjects were treated with once-daily subcutaneous administration of IDeg 100 U/mL prefilled pen along with stable and pre-trial dose of oral antidiabetic drug metformin for 26-weeks. These subjects continued on IDeg + metformin to assess the treatment regimen's ability to sustain long term glycaemic control. No comparisons of endpoints were made between the non-randomised and randomised treatment arms.
OG001	IDeg + Liraglutide	All subjects in this arm were randomised to once-daily subcutaneous administration of IDeg 100 U/mL in a prefilled pen along with once-daily subcutaneous administration of liraglutide (6 mg/mL) in a prefilled pen for 26 weeks of treatment. Subjects continued their oral antidiabetic drug metformin at a stable, pre-trial dose throughout the trial period.

Secondary

Number of Severe and Minor Treatment Emergent Hypoglycaemic Episodes

Corresponds to number of treatment emergent hypoglycaemic events from onset on or after the first day of exposure to investigational product and no later than 7 days after last exposure to investigational product. Confirmed hypoglycaemia was defined as the pool of severe hypoglycaemic episodes and minor episodes with a plasma glucose (PG) value < 3.1 mmol/L (56 mg/dL).

The safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or its comparator

Posted

Number

events

Onset on or after the first day of exposure to investigational product for 26 weeks of treatment period and no later than 7 days after last exposure to investigational product.

ID	Title	Description
OG000	IDeg	This non-randomised arm consisted of subjects treated with IDeg + metformin who achieved the target glycosylated haemoglobin (HbA1c) < 7.0 % at the end of treatment in NN1250-3643. Subjects were treated with once-daily subcutaneous administration of IDeg 100 U/mL prefilled pen along with stable and pre-trial dose of oral antidiabetic drug metformin for 26-weeks. These subjects continued on IDeg + metformin to assess the treatment regimen's ability to sustain long term glycaemic control. No comparisons of endpoints were made between the non-randomised and randomised treatment arms.
OG001	IDeg + Liraglutide	All subjects in this arm were randomised to once-daily subcutaneous administration of IDeg 100 U/mL in a prefilled pen along with once-daily subcutaneous administration of liraglutide (6 mg/mL) in a prefilled pen for 26 weeks of treatment. Subjects continued their oral antidiabetic drug metformin at a stable, pre-trial dose throughout the trial period.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	IDeg	This non-randomised arm consisted of subjects treated with IDeg + metformin who achieved the target glycosylated haemoglobin (HbA1c) < 7.0 % at the end of treatment in NN1250-3643. Subjects were treated with once-daily subcutaneous administration of IDeg 100 U/mL prefilled pen along with stable and pre-trial dose of oral antidiabetic drug metformin for 26-weeks. These subjects continued on IDeg + metformin to assess the treatment regimen's ability to sustain long term glycaemic control. No comparisons of endpoints were made between the non-randomised and randomised treatment arms.	11	236	64	236
EG001	IDeg + Liraglutide	All subjects in this arm were randomised to once-daily subcutaneous administration of IDeg 100 U/mL in a prefilled pen along with once-daily subcutaneous administration of liraglutide (6 mg/mL) in a prefilled pen for 26 weeks of treatment. Subjects continued their oral antidiabetic drug metformin at a stable, pre-trial dose throughout the trial period.	4	87	40	87
EG002	IDeg + IAsp OD	Subjects in this arm were randomised to once-daily subcutaneous administration of IDeg 100 U/mL in prefilled pen along with once-daily subcutaneous administration of insulin aspart (IAsp)100 U/mL in a FlexPen® administered just before the largest meal for 26 weeks of treatment. Subjects continued their oral antidiabetic drug metformin at a stable, pre-trial dose throughout the trial period.	5	86	18	86

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Angina pectoris	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Coronary artery disease	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected236 at risk EG0011 events1 affected87 at risk EG0020 events0 affected86 at risk
Vitreous detachment	Eye disorders	MedDRA	Systematic Assessment	EG0000 events0 affected236 at risk EG0010 events0 affected87 at risk EG0021 events1 affected86 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected236 at risk EG0011 events1 affected87 at risk EG0020 events0 affected86 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected236 at risk EG0010 events0 affected87 at risk EG0021 events1 affected86 at risk
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0001 events1 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Non-cardiac chest pain	General disorders	MedDRA	Systematic Assessment	EG0002 events2 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 events1 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 events0 affected236 at risk EG0010 events0 affected87 at risk EG0021 events1 affected86 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 events0 affected236 at risk EG0010 events0 affected87 at risk EG0021 events1 affected86 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 events1 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 events1 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 events0 affected236 at risk EG0011 events1 affected87 at risk EG0020 events0 affected86 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected236 at risk EG0010 events0 affected87 at risk EG0021 events1 affected86 at risk
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Calculus ureteric	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 events1 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Glomerulonephritis	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 events1 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Hypertensive crisis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 events1 affected236 at risk EG0010 events0 affected87 at risk EG0020 events0 affected86 at risk
Peripheral vascular disorder	Vascular disorders	MedDRA	Systematic Assessment	EG0000 events0 affected236 at risk EG0011 events1 affected87 at risk EG0020 events0 affected86 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00010 events8 affected236 at risk EG00112 events9 affected87 at risk EG0022 events1 affected86 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 events3 affected236 at risk EG00125 events18 affected87 at risk EG0021 events1 affected86 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 events4 affected236 at risk EG0015 events5 affected87 at risk EG0020 events0 affected86 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG00014 events13 affected236 at risk EG0011 events1 affected87 at risk EG0022 events2 affected86 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00054 events43 affected236 at risk EG00111 events9 affected87 at risk EG00212 events11 affected86 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00015 events12 affected236 at risk EG0015 events4 affected87 at risk EG0023 events3 affected86 at risk
Lipase increased	Investigations	MedDRA	Systematic Assessment	EG0000 events0 affected236 at risk EG0017 events6 affected87 at risk EG0020 events0 affected86 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 events2 affected236 at risk EG0015 events5 affected87 at risk EG0021 events1 affected86 at risk

Ancestor Terms

ID	Term
D061266	Insulin, Short-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
D052216	Glucagon-Like Peptide 1
D004763	Glucagon-Like Peptides
D052336	Proglucagon
D005768	Gastrointestinal Hormones

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

ID	Term
C571886	insulin degludec
D061267	Insulin Aspart
D000069450	Liraglutide