A 24-week, multicenter, international, randomized (1:1), parallel-group, open-label, comparative study of insulin glargine versus liraglutide in insulin-naïve patients with Type 2 diabetes treated with oral agents and not adequately controlled, followed by a 24-week extension period with insulin glargine for patients not adequately controlled with liraglutide - EAGLE (Efficacy Assessment of insulin Glargine versus LiraglutidE after oral agents failure)

• Register: EUCTR
• Last refreshed on: 29 April 2013
• Main ID: EUCTR2010-018437-21-NL
• Date of registration: 27/07/2010
• Prospective Registration: Yes
• Primary sponsor: SANOFI AVENTIS GROUPE
• Public title: A 24-week, multicenter, international, randomized (1:1), parallel-group, open-label, comparative study of insulin glargine versus liraglutide in insulin-naïve patients with Type 2 diabetes treated with oral agents and not adequately controlled, followed by a 24-week extension period with insulin glargine for patients not adequately controlled with liraglutide - EAGLE (Efficacy Assessment of insulin Glargine versus LiraglutidE after oral agents failure)
• Scientific title: A 24-week, multicenter, international, randomized (1:1), parallel-group, open-label, comparative study of insulin glargine versus liraglutide in insulin-naïve patients with Type 2 diabetes treated with oral agents and not adequately controlled, followed by a 24-week extension period with insulin glargine for patients not adequately controlled with liraglutide - EAGLE (Efficacy Assessment of insulin Glargine versus LiraglutidE after oral agents failure)
• Date of first enrolment: 16/09/2010
• Target sample size: 930
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-018437-21
• 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: yes Other trial design description: Followed by a 24-week extension period If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Austria, Czech Republic, Finland, France, Ireland, Netherlands, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria for the comparative period:

- Patients aged from 35 to 75 years inclusively,
- With Type 2 Diabetes diagnosed for at least 1 year,
- Treated with lifestyle interventions and metformin at the maximum tolerated dosage (with a minimum daily dosage of 1g), either alone or in combination with an oral insulin secretagogue (sulfonylurea, glinide or DPP-IV inhibitor), for more than 3 months,
- 7.5% < HbA1c = 12%,
- BMI between 25 and 40 kg/m2 inclusively ,
- Ability and willingness to perform PG self monitoring using the sponsor-provided glucose meter and to complete the patient diary,
- Willingness and ability to comply with the study protocol,
- Signed informed consent obtained prior to any study procedure.

Inclusion criteria for the extension period:

- Patients treated with liraglutide (at the maximum tolerated dosage), having a mean FPG = 250 mg/dL at Visit 10 or Visit 11, or a HbA1c = 7% at Visit 12
- Dosage of metformin compliant with the inclusion criterion of Visit 1 (i.e. maximum tolerated dosage, with a minimum daily dosage of 1g), and maintained stable during the comparative period.


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:
Exclusion criteria for the comparative period:

- Previous treatment with GLP-1 analogues or insulin (for in the past year (except in case of temporary treatment for gestational diabetes, surgery,
hospitalization…),
- Treatment with thiazolidinediones or a-Glucosidases inhibitors within 3 months prior to study entry,
- Diabetes other than Type 2 diabetes (e.g. secondary to pancreatic disorders, drug or chemical agents intake…),
- Pregnant women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraceptive method),
- Lactating women,
- Hospitalized patients (except hospitalization for routine diabetes check-up),
- Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to study entry, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study, documented by a retina examination within 2 years prior to study entry,
- Impaired renal function (creatinine clearance < 60 mL/mn),
- Impaired hepatic function (ALT, AST = 2.5 times the upper limit of normal range),
- Personal or family history of medullary thyroid carcinoma,
- Multiple endocrine neoplasia syndrome type 2,
- Severe gastro-intestinal disease (including inflammatory bowel disease or diabetic gastroparesis),
- Congestive heart failure,
- History of acute pancreatitis,
- Treatment with corticosteroids with potential systemic action for more than 10 days within 3 months prior to study entry,
- Alcohol or drug abuse in the past 5 years,
- History of sensitivity to the study drugs or to drugs with a similar chemical structure.
- Night shift worker,
- Presence of any condition (medical, psychological, social or geographical), current or anticipated that would compromise the patient’s safety or limit the patient successful participation in the study.

Exclusion criteria for the extension period:

- Treatment with oral antidiabetic drugs other than metformin and patient’s usual sulfonylurea if any, or with insulin during the comparative period (except in case of an emergency, for a period of time less than 7 days),
- Treatment with corticosteroids with potential systemic action within the last 3 months of the comparative period,
- Pregnant women (women of childbearing potential must have a negative pregnancy test at extension period entry and a medically approved contraception method),
- Lactating women,
- Hospitalized patients (except hospitalization for routine diabetes check-up),
- Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence during the comparative period, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the extension period,
- Impaired renal function (creatinine clearance < 60 mL/mn),
- Impaired hepatic function (ALT, AST = 2.5 times the upper limit of normal range),
- History of sensitivity to insulin glargine.



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

Health Condition(s) or Problem(s) studied

Type 2 diabetes not adequately controlled
MedDRA version: 14.0 Level: LLT Classification code 10063624 Term: Type II diabetes mellitus inadequate control System Organ Class: 10027433 - Metabolism and nutrition disorders

Intervention(s)

Trade Name: Lantus
Pharmaceutical Form: Solution for injection
INN or Proposed INN: INSULIN GLARGINE
CAS Number: 160337951
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Victoza
Pharmaceutical Form: Solution for injection
INN or Proposed INN: LIRAGLUTIDE
CAS Number: 204656-20-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Primary Outcome(s)

Main Objective: The primary objective of this study is to demonstrate the superiority of insulin glargine over liraglutide in terms of percentage of patients reaching a HbA1c < 7% at the end of the comparative period in Type 2 diabetic patients failing lifestyle management and oral agents.

Secondary Objective: The main secondary objectives of this study are to assess the effect of insulin glargine in comparison with liraglutide on:
- HbA1c level
- Percentage of patients whose HbA1c has decreased but remains = 7% at the end of the comparative period
- Percentage of patients whose HbA1c has increased at the end of the comparative period
- Fasting Plasma Glucose (FPG)
- 7-point Plasma Glucose (PG) profiles
- Hypoglycemia occurrence
- Body weight
- Adverse events
- Patient reported outcome measures (PROMs): DTSQs, DTSQc and ADDQoL
- Diabetes specific treatment costs

The objectives of the extension period are to assess the effect of insulin glargine in patients not adequately controlled with liraglutide on:
- HbA1c level
- FPG
- 7-point PG profiles
- Hypoglycemia occurrence
- Body weight
- Adverse events
- PROMs: DTSQs, DTSQc and ADDQoL

Primary end point(s): The main criterion will be the percentage of patients reaching a HbA1c < 7% at the end of the comparative period (visit 12).

Secondary ID(s)

2010-018437-21-CZ

LANTU_C_03680