A 26 week randomised, parallel three-arm, open-label, multi-centre, multinational treat-to-target trial comparing fixed ratio combination of insulin degludec and liraglutide versus insulin degludec or liraglutide alone, in subjects with type 2 diabetes treated with 1-2 oral anti-diabetic drugs (OADs) with a 26 week extension - DUAL I

• Register: EUCTR
• Last refreshed on: 3 June 2013
• Main ID: EUCTR2010-021560-15-DE
• Date of registration: 20/01/2011
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: A 26 week randomised, parallel three-arm, open-label, multi-centre, multinational treat-to-target trial comparing fixed ratio combination of insulin degludec and liraglutide versus insulin degludec or liraglutide alone, in subjects with type 2 diabetes treated with 1-2 oral anti-diabetic drugs (OADs) with a 26 week extension - DUAL I
• Scientific title: A 26 week randomised, parallel three-arm, open-label, multi-centre, multinational treat-to-target trial comparing fixed ratio combination of insulin degludec and liraglutide versus insulin degludec or liraglutide alone, in subjects with type 2 diabetes treated with 1-2 oral anti-diabetic drugs (OADs) with a 26 week extension - DUAL I
• Date of first enrolment: 17/05/2011
• Target sample size: 1660
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-021560-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Finland, Germany, Hungary, Ireland, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
• Subjects with type 2 diabetes
• HbA1c 7.0-10.0 % (both inclusive) with the aim of a median HbA1c of 8.3%. Accordingly, when approximately 50% of the randomised subjects have a HbA1c above 8.3%, the remaining subjects randomised must have a HbA1c of below or equal to 8.3%, or when approximately 50% of the randomised subjects have a HbA1c of below or equal to 8.3%, the remaining subjects randomised must have a HbA1c above 8.3%
• Male or female, age 18 years or above
• Subjects on stable dose of 1-2 OADs (metformin [= 1500 mg or max tolerated dose] or metformin [= 1500 mg or max tolerated dose] + pioglitazone [= 30 mg]) for at least 90 days prior to screening
• BMI = 40 kg/m^2
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Treatment with insulin (except for short-term treatment due to intercurrent illness at the discretion of the Investigator)
• Treatment with GLP-1 receptor agonists (eg exenatide, liraglutide), sulphonylurea or dipeptidyl peptidase 4 (DPP-4) inhibitors within 90 days prior to trial
• Impaired liver function, defined as alanine aminotransferese (ALAT) = 2.5 times Upper Normal Range (UNR) (one retest analysed at the central laboratory within a week from first sample taken is permitted with the result of the last sample being the conclusive)
• Impaired renal function defined as serum-creatinine = 133 µmol/l (= 1.5 mg/dl) for males and = 125 µmol/l (= 1.4) for females, or as allowed according to local contraindications for metformin (one retest analysed at the central laboratory within a week from first sample taken is permitted with the result of the last sample being the conclusive)
• Screening calcitonin = 50 ng/L
• Subjects with personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2)
• Cardiac disorder defined as: congestive heart failure (NYHA class III-IV), diagnosis of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the last 12 months and planned coronary, carotid or peripheral artery revascularisation procedures
• Severe uncontrolled treated or untreated hypertension (systolic blood pressure = 180 mm Hg or diastolic blood pressure = 100 mm Hg)
• Acute treatment required proliferative retinopathy or maculopathy (macular oedema)
• History of chronic pancreatitis or idiopathic acute pancreatitis


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type 2 diabetes
MedDRA version: 14.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Intervention(s)

Product Name: Insulin degludec/liraglutide
Product Code: NNC 0100-0454/ NNC 90-1170
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Insulin degludec
CAS Number: 844439-96-9
Current Sponsor code: NNC 0100-0454
Other descriptive name: Insulin 454
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: Liraglutide
CAS Number: 204656-20-2
Current Sponsor code: NN 90-1170
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 3.6-

Product Name: Insulin degludec
Product Code: NNC 0100-0454
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Insulin degludec
CAS Number: 844439-96-9
Current Sponsor code: NNC 0100-0454
Other descriptive name: Insulin 454
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Victoza
Product Code: NNC 90-1170
Pharmaceutical Form: Solution for injection
INN or Proposed INN: LIRAGLUTIDE
CAS Number: 204656-20-2
Current Sponsor code: NNC 90-1170
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6.0-

Primary Outcome(s)

Primary end point(s): Change from baseline in HbA1c after 26 weeks of treatment

Secondary Objective: • To confirm superiority of insulin degludec/liraglutide vs insulin degludec after 26 weeks of treatment on either weight control, hypoglycaemic episodes, glycaemic control in relation to a meal, or glycaemic control as indirectly measured by daily dose of insulin degludec
• To compare general efficacy and safety of insulin degludec/liraglutide, insulin degludec and liraglutide after 26 and 52 weeks of treatment
• To confirm the efficacy of insulin degludec/liraglutide in controlling glycaemia in subjects with type 2 diabetes after 52 weeks of treatment

Main Objective: To confirm the efficacy of insulin degludec/liraglutide in controlling glycaemia in subjects with type 2 diabetes.

This is done by comparing the difference in change in HbA1c from baseline after 26 weeks of treatment to a non-inferiority limit of 0.3% for insulin degludec/liraglutide vs insulin degludec and to a superiority limit of 0% for insulin degludec/liraglutide vs liraglutide.

Secondary ID(s)

2010-021560-15-GB

NN9068-3697