baSal BoluS Therapy in patIenTs With TypE 1 Diabetes Mellitus (SUBSTITUTE)

• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

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

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 1	Drug: INSULIN GLARGINE; Drug: INSULIN GLULISINE	Phase 4

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).

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	206 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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.
Study Start Date :	November 2010
Actual Primary Completion Date :	January 2013
Actual Study Completion Date :	January 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Insulin glargine + insulin glulisine; 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; Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: once a day at bedtime; Other Name: Lantus SoloStar; Drug: INSULIN GLULISINE; Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: three times a day, preferably just before the meal; Other Name: Apidra SoloStar

Outcome Measures

Primary Outcome Measures :

1. Change in hemoglobin A1c (HbA1c) values (following the reference of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)) [ Time Frame: between baseline (week 0) and endpoint (week 24) ]

Secondary Outcome Measures :

1. Change of HbA1c [ Time Frame: from baseline to week 12 ]
2. Percentage of patients with HbA1c < 7% [ Time Frame: at week 12 and week 24 ]
3. Fasting Blood Glucose (FBG) [ Time Frame: at baseline, week 12 and week 24 ]
4. 7-point Self Monitoring of Blood Glucose (SMBG) [ Time Frame: at baseline, week 12 and week 24 (to be performed the week preceding each visit on two consecutive days) ]
5. Daily dose for insulin glulisine [ Time Frame: At baseline, week 12 and week 24 ]
6. Daily dose for insulin glargine [ Time Frame: At baseline, week 12 and week 24 ]
7. Symptomatic hypoglycemias [ Time Frame: From baseline (week 0) to endpoint (week 24) ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

1. 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
2. Age: 18-60 years inclusive
3. HbA1c: 8% - 10% assessed over the past 6 month
4. At least 1 year of continuous insulin treatment

5. 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
6. Signed informed consent obtained prior to any study procedure

Criteria for entry in the treatment period:

1. HbA1c 8-10% assessed between week -2 and week 0
2. Serum creatinine ≤135 micromol/L in men and ≤110 micromol/L in women
3. Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) lower or equal to three times the upper limit of normal
4. Pregnancy test negative if women of childbearing potential

Exclusion criteria:

1. History of hypersensitivity to insulin glargine and/or insulin glulisine
2. Pregnant, breast-feeding or women of childbearing potential not using efficient contraception
3. Brittle diabetes
4. Known impaired renal function defined as serum creatinine > 135 micromol/L in men and > 110 micromol/L in women at study entry
5. 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
6. Diabetes ketoacidosis
7. History of drug or alcohol abuse
8. Psychiatric or mental disease
9. Inclusion in another study in the past 6 months or previous inclusion in this study
10. 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.

Contacts and Locations

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Sponsors and Collaborators

Sanofi

Investigators

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Study Director:	Clinical Sciences & Operations	Sanofi

More Information

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Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT01204593 History of Changes
Other Study ID Numbers:	LANTU_R_05033; U1111-1116-3450 ( Other Identifier: WHO )
First Posted:	September 17, 2010
Last Update Posted:	March 17, 2014
Last Verified:	March 2014

Additional relevant MeSH terms:

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Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases	Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin glulisine; Hypoglycemic Agents; Physiological Effects of Drugs