Insulins Glargine and gluLisine strAtegy Versus Premixed Insulin strAteGy: a cOmparative Study

Study Overview
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Brief Summary
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Primary Objective: To demonstrate the superiority of a strategy with insulin glargine in comparison with a strategy including the premixed insulin in term of percentage of patients reaching HbA1c (glycosylated hemoglobin) below 7% at the end of treatment and who do not experience documented symptomatic hypoglycemia (confirmed by a Plasma Glucose (PG) below 56 mg/dL (3.1 mmol/L)) over a 24-week treatment period, in Type 2 diabetes patients failing lifestyle management and oral agents. Secondary Objectives: To assess the effect of insulin glargine in comparison with premixed insulin on : Evolution of HbA1c level during the treatment period Percentage of patients who reach the target of HbA1c < 7 % and who do not experience documented symptomatic hypoglycemia confirmed by a Plasma Glucose (PG) below 70 mg/dL (3.9 mmol/L) Percentage of patients who reach the target of HbA1c < 6.5% and who do not experience documented symptomatic hypoglycemia confirmed by a PG below 56 mg/dL (3.1 mmol/L) >Percentage of patients who reach the target of HbA1c < 6.5% and who do not experience documented symptomatic hypoglycemia confirmed by a PG below 70 mg/dL (3.9 mmol/L) >Evolution of Fasting Plasma Glucose Evolution of 7-point plasma glucose profiles Evolution of weight Hypoglycemia occurrence Dose of insulins Evolution of liver function Overall safety

Official Title
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A 24-week, Open, Multicenter, Comparative Study of 2 Strategies (Including Insulin Glargine Versus Premixed Insulin) for the Therapeutic Management of Patients With Type 2 Diabetes Failing Oral Agents

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: INSULIN GLARGINE
* Drug: INSULIN GLULISINE
* Drug: PREMIXED INSULIN


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Type 2 diabetes diagnosed for more than 1 year Insulin naïve Treated with lifestyle interventions and oral antidiabetic drugs, at least metformin at the maximum tolerated dose (with a minimum dose of 1g/day), for at least 3 months HbA1c ≥ 7.0 % and ≤ 10.5% Body mass index (BMI) ≤ 40 kg/m2 Ability and willingness to perform plasma glucose (PG) 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 any study procedure Exclusion criteria: Treatment with glucagon-like peptide-1 (GLP-1) agonists in the 3 months prior to study entry Previous treatment with insulin (except for treatment of gestational diabetes or brief treatment with insulin for less than 1 week) Diabetes other than type 2 diabetes (e.g. type 1 diabetes, diabetes secondary to pancreatic disorders, drug or chemical agent intake) Pregnant or lactating women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method) Hospitalized patient (except 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 retina examination, in the 2 years prior to study entry History of sensitivity to the study drugs or to drugs with a similar chemical structure Impaired renal function: creatinine clearance < 60ml/min Impaired liver function (ALT, AST > 3 x upper limit of normal range) Severe gastro-intestinal disease Treatment with corticosteroids with potential systemic action within the 3 months prior to study entry Likelihood of requiring treatments during the study which are not permitted Treatment with an investigational product in the 30 days prior to study entry Alcohol or drug abuse within the last 5 years The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin glargine<br>Administered once a day in the evening, at the same time every day. The starting daily dose is 0.2 U/Kg of body weight or 12 U, at the investigator's decision. Insulin glulisine is administered for patients of the insulin glargine group requiring insulin glulisine at week 12 (visit 11). Insulin glulisine is administered prior (10-15 min) to the main meal of the day, which is the meal with highest Post-Prandial Plasma Glucose (PPPG) on the 3 profiles performed before week 12. Starting dose is of 4 units per day. | Drug: INSULIN GLARGINE<br>* Pharmaceutical form: solution for injection Route of administration: sub-cutaneous injection Dose regimen: 100 Units/mL solution for injection in a pre-filled SoloStar pen (3 ml)<br>Drug: INSULIN GLULISINE<br>* Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: 100 Units/mL solution for injection in a pre-filled SoloStar pen (3 mL)<br>|
| Experimental: Premixed insulin<br>administered once a day (in the evening at dinner) or twice a day (in the morning before breakfast and in the evening at dinner). Starting daily dose will be 6 U at breakfast and 6 U at dinner, if administered twice a day or 12 U at dinner if administered once a day | Drug: PREMIXED INSULIN<br>* Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: - 30% soluble insulin aspart and 70 % protamine-crystallised insulin aspart in pre-filled Flexpen for all the countries except Mexico 25 % insulin lispro solution and 75% insulin lispro protamine in cartridges for Humapen Luxura for Mexico only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with Glycosylated Haemoglobin (HbA1c) <7% with no documented symptomatic hypoglycemia (confirmed by a Plasma Glucose (PG) ≤ 56 mg/dL [3.1 mmol/L] |  | From baseline (visit 2, week 0) to visit 14 (week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-point plasma glucose (PG) profile recorded on 3 consecutive days |  | From baseline (visit 2, week 0) to visit 14 (week 24) | 
| Self-monitored PG (Plasma Glucose) values over 3 consecutive days |  | before visit 4 (week 2) | 
| Self-monitored PG (Plasma Glucose) values over 3 consecutive days |  | before visit 8 (week 6) | 
| Self-monitored PG (Plasma Glucose) values over 3 consecutive days |  | before visit 12 (week 16) | 
| Weight and supine blood pressure |  | From baseline (visit 2, week 0) to visit 14 (week 24) | 
| Insulin doses of the day before each visit |  | from visit 3 (week 1) to visit 14 (week 24) | 
| Biochemistry and lipid profile |  | From baseline (visit 2, week 0) to visit 14 (week 24) |