Official 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 Insulin Glargine or Insulin Detemir.”

Primary 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) ≤ 56 mg/dL (3.1 mmol/L)

Secondary objectives: - To compare between the 2 treatment groups, the percentage of patients who reach the target of HbA1c < 7% and < 6.5% at the end of the treatment period - To compare the changes in HbA1c and fasting plasma glucose (FPG) - To compare the evolution of blood glucose profiles - To compare the day to day FPG variability, the insulin doses - To determine in each treatment group the biochemical and patient-related determinants of failure to reach HbA1c targets - To compare the overall incidence and rate of symptomatic hypoglycemia and nocturnal symptomatic hypoglycemia confirmed by PG ≤ 56 mg/dL (3.1 mmol/L) - To compare over the treatment period, the overall incidence and rate of symptomatic hypoglycemia and symptomatic nocturnal hypoglycemia (with PG ≤ 70 mg/dL [3.9 mmol/L]), of symptomatic day-time hypoglycemia (with PG ≤ 70 mg/dL and with PG ≤ 56 mg/dL), of severe hypoglycemia, of asymptomatic hypoglycemia with PG ≤ 56 mg/dL - To compare the overall safety: incidence of adverse events (including serious hypoglycemia and local tolerance at injection site), change in body weight, in waist circumference and in waist / hip ratio - To assess the quality of life and treatment satisfaction

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2008

Intervention(s) in this Clinical Trial

• Drug: Insulin glargine
  • Subcutaneous injection, once a day in the evening
• Drug: Insulin Detemir
  • Subcutaneous injection, twice a day at breakfast and before dinner

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Insulin Glargine
• Active Comparator: 2
  • Insulin Detemir

Primary Measures

• HbA1c recorded
  • Time Frame: At baseline, week 12 and week 24
    Safety Issue?: No
• Self-monitored fasting BG in both treatment arms and pre-dinner BG in detemir arm
  • Time Frame: On the 4 consecutive days before each visit
    Safety Issue?: No
• Self-monitored BG values from 8-point 24-hour profile recorded on 2 consecutive days
  • Time Frame: Within the week prior to baseline, week 12 and week 24
    Safety Issue?: No
• Episodes of hypoglycemia (symptomatic, total and categorized as day-time/nocturnal, severe or asymptomatic)
  • Time Frame: All across the study
    Safety Issue?: No
• Self-monitored BG values whenever patient experiences symptoms possibly related to hypoglycemia.
  • Time Frame: All across the study
    Safety Issue?: No

Secondary Measures

• Doses of insulin glargine or insulin detemir
  • Time Frame: Daily
    Safety Issue?: No
• Laboratory fasting plasma glucose
  • Time Frame: At baseline, week 12 and week 24
    Safety Issue?: No
• Insulinemia and fasting C-peptide level
  • Time Frame: At baseline
    Safety Issue?: No
• Lipid profile
  • Time Frame: at baseline and week 24
    Safety Issue?: No
• Patient reported outcomes (quality of life and treatment satisfaction)
  • Time Frame: at baseline, week 4, week 12 and at the last visit
    Safety Issue?: No
• Safety data: occurrence of adverse events and weight
  • Time Frame: assessed at each visit
    Safety Issue?: Yes
• Waist and hip circumferences
  • Time Frame: measured at baseline, week 12 and week 24
    Safety Issue?: No
• Systolic and diastolic blood pressure
  • Time Frame: measured at study entry, baseline, week 12 and week 24
    Safety Issue?: No
• Physical examination
  • Time Frame: performed at study entry and at last visit.
    Safety Issue?: No

Inclusion Criteria:

• Type 2 diabetes for at least 1 year
• Insulin naïve
• Treated with stable doses of oral antidiabetics for at least 3 months prior to study start, including at least metformin (at least 1g/day)
• 7% ≤ HbA1c ≤ 10.5 %
• Body mass index (BMI) < 40 kg/m²
• Ability and willingness to perform blood glucose monitoring using a blood glucose meter and to use a patient diary

Exclusion Criteria:

• Type 1 diabetes
• Current or previous use of insulin (except for previous treatment of gestational diabetes or brief treatment with insulin for less than 1 week)
• Treatment with glucagon-like peptide (GLP)-1 receptor agonists or with dipeptidyl peptidase (DPP)-IV inhibitors
• 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)
• Pregnancy (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraceptive method)
• Breast-feeding
• History of hypersensitivity to the study drugs or to drugs with a similar chemical structure
• Treatment with systemic corticosteroids in the 3 months prior to study entry
• Treatment with any investigational product in the 2 months prior to study entry
• Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol
• Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major disease making implementation of the protocol or interpretation of the study results difficult
• 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
• 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
• History of drug or alcohol abuse in the last year
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sanofi-Aventis

Overall Clinical Trial Officials and Contacts

Valérie Pilorget Study Director Sanofi-Aventis  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00405418

Study ID Number: LANTU_C_00579

ClinicalTrials.gov Identifier: NCT00405418

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)