baSal BoluS Therapy in patIenTs With TypE 1 Diabetes Mellitus

Study Overview
=================
Brief Summary
-----------------
Primary Objective: To evaluate the efficacy of the association Lantus (once-a-day, od) Apidra (thrice-a-day, tid) in terms of change HbA1c from baseline to end of study (week 24), in patients with Type 1 Diabetes Mellitus (T1DM). Secondary Objectives: To evaluate: The change of hemoglobin A1c (HbA1c) from baseline to week 12 The percentage of patients with HbA1c < 7% at week 12 and week 24 The FBG and the 7-point self monitoring of blood glucose (SMBG) at baseline, week 12 and week 24 The daily dose for both insulin glulisine insulin glargine at baseline, week 12 and week 24 The incidence of symptomatic hypoglycemias Adverse events

Detailed Description
-----------------
After a two-week run-in period patients will enter a six-month treatment period. Estimated study duration per patient : 26 weeks (including a 2-week run-in period).

Official Title
-----------------
Phase IV, Multicenter, International, Non-comparative, Open Label Study of Efficacy and Safety of Basal Bolus Therapy (Insulin Glargine + Insulin Glulisine) in Patients With T1 Diabetes Previously Uncontrolled on Any Insulin Regimen.

Conditions
-----------------
Diabetes Mellitus, Type 1

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Known Type 1 diabetic patients (male or female) treated with any type of insulin regimen, except: continuous subcutaneous insulin infusion (CSII, or pump), and patients already treated with insulin glargine Age: 18-60 years inclusive HbA1c: 8% - 10% assessed over the past 6 month At least 1 year of continuous insulin treatment Willingness to accept, and ability to follow: a basal bolus regimen (glargine x1 and glulisine x3 per day), self-monitoring blood glucose (SMBG) a fixed meal plan, or CHO counting Signed informed consent obtained prior to any study procedure Criteria for entry in the treatment period: HbA1c 8-10% assessed between week -2 and week 0 Serum creatinine ≤135 micromol/L in men and ≤110 micromol/L in women Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) lower or equal to three times the upper limit of normal Pregnancy test negative if women of childbearing potential Exclusion criteria: History of hypersensitivity to insulin glargine and/or insulin glulisine Pregnant, breast-feeding or women of childbearing potential not using efficient contraception Brittle diabetes Known impaired renal function defined as serum creatinine > 135 micromol/L in men and > 110 micromol/L in women at study entry Known impaired hepatic function defined as Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) greater than three times the upper limit of normal at study entry Diabetes ketoacidosis History of drug or alcohol abuse Psychiatric or mental disease Inclusion in another study in the past 6 months or previous inclusion in this study Patient unable or unwilling to manage properly the basal bolus regimen 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
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin glargine + insulin glulisine<br>Insulin glargine dosage will be individually titrated once a week to obtain FPG 80-120 mg/dL (4.5-6.7 mmol/L). Insulin glulisine dosage will be individually titrated once a week to obtain a 2-hour postprandial plasma glucose (PPG) < 180 mg/dL (<10.0 mmol/L) and ideally around 140 mg/dL. | Drug: INSULIN GLARGINE<br>* Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: once a day at bedtime<br>* Other names: Lantus SoloStar;Drug: INSULIN GLULISINE<br>* Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: three times a day, preferably just before the meal<br>* Other names: Apidra SoloStar;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemoglobin A1c (HbA1c) values (following the reference of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)) |  | between baseline (week 0) and endpoint (week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of HbA1c |  | from baseline to week 12 | 
| Percentage of patients with HbA1c < 7% |  | at week 12 and week 24 | 
| Fasting Blood Glucose (FBG) |  | at baseline, week 12 and week 24 | 
| 7-point Self Monitoring of Blood Glucose (SMBG) |  | at baseline, week 12 and week 24 (to be performed the week preceding each visit on two consecutive days) | 
| Daily dose for insulin glulisine |  | At baseline, week 12 and week 24 | 
| Daily dose for insulin glargine |  | At baseline, week 12 and week 24 | 
| Symptomatic hypoglycemias |  | From baseline (week 0) to endpoint (week 24) |