Comparison of Two Treatment Regimens in Patients With Type 2 Diabetes After Short-term Intensive Insulin Therapy

Study Overview
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Brief Summary
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Primary Objective: To test the hypothesis that basal insulin based treatment (G+) is noninferior to twice-daily premixed insulin (PM-2) in term of hemoglobin A1c (glycosylated hemoglobin, HbA1c) reduction from baseline to end of study. The test for superiority can be done if noninferiority is achieved. Secondary Objectives: To assess efficacy in terms of percentage of patients achieving HbA1c <7% and HbA1c <7% without hypoglycemia. To assess efficacy in terms of percentage of patients achieving fasting plasma glucose (FPG) <7 mmol/L and FPG <7 mmol/L without hypoglycemia. To assess safety in term of occurrence of moderate/severe hypoglycemia. To assess daily blood glucose (BG) variation. To assess patient satisfaction.

Detailed Description
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The duration of study is approximately 21 months. Each patient will be followed for approximately 27 weeks from screening visit to end-of-study

Official Title
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A 26-Week, Multi-Center, Open-label, Randomized, Parallel-group Study to Evaluate the Efficacy and Safety of Two Treatment Regimens in Patients With Type 2 Diabetes After Short-Term Intensive Insulin Therapy: Basal Insulin Based Treatment (With Prandial OADs Combination) Versus Twice-daily Premixed Insulin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: INSULIN GLARGINE (HOE901)
* Drug: Insulin Glulisine
* Drug: Biphasic insulin aspart 30
* Drug: Repaglinide
* Drug: Acarbose
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Patients with age between 18 and 70 years. Hemoglobin A1c>7.5%, and ≤11%. Fasting plasma glucose >7 mmol/L. Fasting C peptide >1 ng/mL. Type 2 diabetes (T2DM) patients with diabetes diagnosis between 2 and 10 years (World Health Organization 1999 T2DM diagnose criteria). Continuous treatment with stable doses of metformin (≥1 g/day) and 1 oral antihyperglycemic drug (at least half maximum dose) for more than 3 months prior to screening. Body mass index ≥21 kg/m2, and <40 kg/m2. Exclusion criteria: More than 7 consecutive days of insulin treatment within the 12 months except for acute disease or surgery. Diabetes other than T2DM (e.g. type 1 diabetes, diabetes secondary to pancreatic disorders, drug or chemical agent intake). History of hypoglycemia unawareness or recurrent hypoglycemia or severe hypoglycemia within the past 12 months. History of sensitivity to the study drugs or to drugs with a similar chemical structure. Pregnancy or planned pregnancy or current lactation (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method). Acute diabetic complications (diabetic ketoacidosis, lactic acidosis, hyperosmolar nonketotic diabetic coma) within the past 12 months. Significant diabetic complications and serious disease, e.g., symptomatic autonomic neuropathy, gastroparesis, unstable angina or active proliferative retinopathy. Acute infections which may affect BG control within the past 4 weeks. Active liver disease, alanine transaminase (ALT) and/or aspartate aminotransferase (AST) greater than two times the upper limit of the reference range at screening. Impaired renal function, defined as but not limited to, serum creatinine levels ≥1.5 mg/dL (132 μmol/L) for males and ≥1.4 mg/dL (123 μmol/L) for females or presence of macroproteinuria (>2 g/day). 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: 18 Years
Maximum Age: 70 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: Glargine based therapy<br>Once daily glargine plus prandial oral anti-hyperglycemic drugs | Drug: INSULIN GLARGINE (HOE901)<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous injection<br>* Other names: Lantus;Drug: Insulin Glulisine<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous injection<br>* Other names: Apidra;Drug: Repaglinide<br>* Pharmaceutical form: tablet Route of administration: oral administration<br>* Other names: NovoNorm;Drug: Acarbose<br>* Pharmaceutical form: tablet Route of administration: oral administration<br>* Other names: Glucobay;|
| Active Comparator: Premixed insulin<br>Twice daily premixed insulin | Drug: Biphasic insulin aspart 30<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous injection<br>* Other names: Novolog Mix70/30;Drug: Metformin<br>* Pharmaceutical form: tablet or capsule Route of administration: oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemoglobin A1c (HbA1c) | Change in HbA1c from baseline to week 24 | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients with fasting plasma glucose (FPG) <6.1 mmol/L | Percentage of patients with FPG <6.1 mmol/L at week 12 and week 24 | At Week 12 and Week 24 | 
| Patients with FPG <6.1 mmol/L without hypoglycemia | Percentage of patients with FPG <6.1 mmol/L without hypoglycemia at week 12 and week 24 | At Week 12 and Week 24 | 
| Patients with FPG <7 mmol/L | Percentage of patients with FPG <7 mmol/L at week 12 and week 2 | At Week 12 and Week 24 | 
| Patients with FPG <7 mmol/L without hypoglycemia | Percentage of patients with FPG <7 mmol/L without hypoglycemia at week 12 and week 24 | At Week 12 and Week 24 | 
| Patients with HbA1c <7% | Percentage of patients with HbA1c <7% at week 12 and week 24 | At Week 12 and Week 24 | 
| Patients with HbA1c <7% without hypoglycemia | Percentage of patients with HbA1c <7% without hypoglycemia at week 12 and week 24 | At Week 12 and Week 24 | 
| Hypoglycemic events | Incidence of hypoglycemia during treatment period | Baseline to Week 24 | 
| Change in FPG | Change in FPG from baseline to week 24 | Baseline to Week 24 | 
| Change in body weight | Change in body weight from baseline to week 24 | Baseline to Week 24 | 
| Insulin dose | Total daily insulin dose at week 24 | At Week 24 | 
| Daily BG variation at week 24 | Daily blood glucose (BG) variation at week 24 | At Week 24 | 
| European quality of life - 5 dimensions (EQ-5D) | Change in quality of life scores from baseline to week 24 on 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is measured at 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problem. | Baseline to Week 24 | 
| Subgroup analysis | Subgroup analysis of control rate of HbA1c <7% according to duration of diabetes, oral anti-hyperglycemic drug(OAD) treatment and HbA1c at screening, FPG, post prandial glucose(PPG) excursion and C peptide at the beginning of run-in period, insulin dose at end of run-in period | At week 24 |