TARGET GLYCEMIC CONTROL AND THE INCIDENCE OF DOCUMENTED SYMPTOMATIC HYPOGLYCEMIA IN INSULIN NAÏVE SUBJECTS WITH TYPE 2 DIABETES FAILING ON ORAL HYPOGLYCEMIC AGENT(S) AND TREATED WITH LANTUS (INSULIN GLARGINE) OR LEVEMIR (INSULIN DETEMIR): MULTICENTER, MULTINATIONAL, RANDOMIZED, OPEN-LABEL, COMPARATIVE, PARALLEL-GROUP STUDY - L2T3

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-000324-13-DK
• Date of registration: 11/08/2006
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis groupe
• Public title: TARGET GLYCEMIC CONTROL AND THE INCIDENCE OF DOCUMENTED SYMPTOMATIC HYPOGLYCEMIA IN INSULIN NAÏVE SUBJECTS WITH TYPE 2 DIABETES FAILING ON ORAL HYPOGLYCEMIC AGENT(S) AND TREATED WITH LANTUS (INSULIN GLARGINE) OR LEVEMIR (INSULIN DETEMIR): MULTICENTER, MULTINATIONAL, RANDOMIZED, OPEN-LABEL, COMPARATIVE, PARALLEL-GROUP STUDY - L2T3
• Scientific title: TARGET GLYCEMIC CONTROL AND THE INCIDENCE OF DOCUMENTED SYMPTOMATIC HYPOGLYCEMIA IN INSULIN NAÏVE SUBJECTS WITH TYPE 2 DIABETES FAILING ON ORAL HYPOGLYCEMIC AGENT(S) AND TREATED WITH LANTUS (INSULIN GLARGINE) OR LEVEMIR (INSULIN DETEMIR): MULTICENTER, MULTINATIONAL, RANDOMIZED, OPEN-LABEL, COMPARATIVE, PARALLEL-GROUP STUDY - L2T3
• Date of first enrolment: 19/10/2006
• Target sample size: 910
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-000324-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: Double blind: Parallel group: yes Cross over: Other: If controlled, specify comparator, Other Medicinial Product: yes Placebo: Other:

Countries of recruitment

Denmark, Finland, Germany, Ireland, Netherlands, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Men or women, aged from 40 to 75 years inclusive
2. Type 2 diabetes for at least 1 year
3. Insulin naïve
4. Treated with stable doses of OADs for at least 3 months prior to study start, including at least metformin (at least 1g/day)
5. 7% <= HbA1c <=10.5 %
6. Body mass index (BMI) < 40 kg/m2
7. Ability and willingness to perform blood glucose monitoring using a blood glucose meter and to use a patient diary
8. Written informed consent obtained prior to enrollment in the study

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:
1. Type 1 diabetes
2. Current or previous use of insulin (except for previous treatment of gestational diabetes or brief treatment with insulin for less than 1 week)
3. Treatment with GLP-1 receptor agonists or with DPP-IV inhibitors
4. Active proliferative diabetic retinopathy, as defined by the application of photocoagulation or surgery, in the 6 months before study entry or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgery during the study (an optic fundus examination should have been performed in the 2 years prior to study entry)
5. Pregnancy (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraceptive method)
6. Breast-feeding
7. History of hypersensitivity to the study drugs or to drugs with a similar chemical structure
8. Treatment with systemic corticosteroids in the 3 months prior to study entry
9. Treatment with any investigational product in the 2 months prior to study entry
10. Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol
11. Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major disease making implementation of the protocol or interpretation of the study results difficult
12. Impaired hepatic function as shown by Alamine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) greater than three times the upper limit of normal range at study entry
13. Impaired renal function as shown by serum creatinine >=1.5 mg/dL (>= 133 µmol/L) in men and >= 1.4 mg/dL (124 µmol/L) in women at study entry
14. History of drug or alcohol abuse in the last year
15. Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
16. Patient unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits and unlikelihood of completing the study
17. Patient is the investigator or any sub-investigator, research assistant, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol




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

Health Condition(s) or Problem(s) studied

Type II diabetes mellitus
MedDRA version: 8.1 Level: LLT Classification code 10045242

Intervention(s)

Trade Name: LANTUS 100IU/ml solution for injection in a cartridge
Product Name: Lantus 100 IU/ml, solution for injection in a cartridge
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Insulin glargine
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: -100

Trade Name: LEVEMIR 100U/ml solution for injection in a cartridge
Product Name: Levemir 100 U/ml solution for injection in a cartridge
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Insulin detemir
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: -100

Primary Outcome(s)

Primary end point(s): Data collected for the assessment of primary and main secondary endpoints:
• HbA1c recorded at baseline, week 12 and week 24
• Self-monitored fasting BG in both treatment arms and pre-dinner BG in detemir arm on the 4 consecutive days before each visit
• Self-monitored blood glucose values from 8-point 24-hour profile (immediately before and 2 hours after breakfast, lunch and dinner, at bedtime and at 3:00 a.m.) recorded on 2 consecutive days within the week prior to randomization visit 2 (baseline), visit 12 (week 12) and last visit (week 24). In this protocol, bedtime should be at least 2 hours and 30 minutes after dinner
• Episodes of hypoglycemia (symptomatic hypoglycemia, total and categorized as day-time/nocturnal, severe hypoglycemia, asymptomatic hypoglycemia)
• Self-monitored blood glucose values whenever the patient experiences symptoms possibly related to hypoglycemia
• Daily doses of insulin glargine or insulin detemir
• Laboratory fasting plasma glucose at baseline, week 12 and week 24
• Insulinemia and fasting C-peptide level at baseline
• Lipid profile at baseline and week 24
• Patient reported outcomes (quality of life and treatment satisfaction) will be assessed at baseline, week 4, week 12 and at the last visit, using: the Fear of hypoglycemia score (in the Netherlands and Germany, Australia and UK), the DSC-R and the WHO-5 (in selected countries), and the DTSQ questionnaires
• Safety data: occurrence of adverse events and weight will be assessed at each visit. Waist and hip circumferences will be measured at baseline, week 12 and week 24. Systolic and diastolic blood pressure will be measured at study entry, baseline, week 12 and week 24. A physical examination will be performed at study entry and at the last visit.

Secondary Objective: To compare :
• between the 2 trt groups, the % of pts who reach the target of HbA1c < 7% and < 6.5% at the end of the treatment period
• the changes in HbA1c and FPG
• the evolution of blood glucose profiles
• the day to day FPG variability, the insulin doses
• the overall incidence , rate of symptomatic hypoglyc. and nocturnal symptomatic hypoglyc.confirmed by PG < = 56 mg/dL
• over the trt period, the overall incidence and rate of symptomatic hypoglyc. and symptomatic nocturnal hypoglyc. (with PG< =70 mg/dL , of symptomatic day-time hypoglyc. (with PG < =70 mg/dL and with PG < = 56 mg/dL), of severe hypoglycemia, of asymptomatic hypoglyc. with PG < =56 mg/dL
• the overall safety: incidence of AE (including serious hypoglyc. and local tolerance at injection site), change in body weight, in waist circumference and in waist / hip ratio

To determine the biochemical and patient-related determinants of failure to reach HbA1c targets

To assess the QoL and trt satisfaction

Main Objective: To demonstrate the non-inferiority of insulin glargine in comparison to insulin detemir in term of percentage of patients who reach the target of HbA1c < 7% at the end of the treatment period and do not experience symptomatic hypoglycemia, confirmed by plasma glucose (PG) inferior or equal to 56 mg/dL (3.1 mmol/L)

Secondary ID(s)

LANTU-C-00579

2006-000324-13-IE