Opposing Step-by-step Insulin Reinforcement to Intensified Strategy

Diabetes Mellitus, Type 2 Clinical Trial

— OSIRIS  

Official title:

Comparison of Three Therapeutic Strategies for Treating Type 2 Diabetes Mellitus Patients Poorly Controlled With Basal Insulin Associated With Oral Antidiabetic Drugs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00174642
• Other study ID #: HMR1964A_3506
• Secondary ID: EUDRACT # : 2004
• Status: Completed
• Phase: Phase 3
• First received: September 9, 2005
• Last updated: September 14, 2009
• Start date: December 2004

Study information

• Verified date: September 2009
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

Primary objectives :

• To show the non inferiority in terms of efficacy (HbA1c) of insulin glargine plus metformin combined with 1 to 3 bolus of insulin glulisine introduced progressively (Arm 2) compared with insulin glargine plus metformin combined with 3 bolus of insulin glulisine (Arm 1), in type 2 diabetes mellitus patients poorly controlled on basal insulin therapy with oral antidiabetic drugs.

• To show the non inferiority in terms of efficacy (HbA1c) of insulin glargine plus metformin combined with 1 to 3 bolus of insulin glulisine introduced progressively (Arm 2) compared with insulin glargine plus metformin and insulin secretagogue (sulfonylurea or glinide) combined with 1 to 3 bolus of insulin glulisine introduced progressively (Arm 3), in type 2 diabetes mellitus patients poorly controlled on basal insulin therapy with oral antidiabetic drugs.

Secondary objectives :

• To compare between the 3 treatment groups: evolution of HbA1c over time, percentage of subjects with HbA1c <= 7% at the end of the study, evolution of blood glucose profiles, incidence of hypoglycemia, insulin doses, evolution of body weight and treatment satisfaction.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 811
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

• Type 2 diabetic

• BMI = 40 kg/m²

• HbA1c > 7%

• Treated with basal insulin (NPH, Insulin Zinc, insulin glargine or insulin detemir), and at least, two OAD including an insulin secretagogue (sulfonylurea or glinide, at any dosage) and metformin (at the maximum tolerated dosage), for more than 6 months

Exclusion criteria:

• Type 1 diabetes mellitus

• Treatment with OADs only

• Treatment with thiazolidinediones

• Treatment with an insulin other than basal insulin (Premix, rapid insulin, fast-acting insulin analogue)

• 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 (confirmed by an optic fundus performed in the 2 years prior study entry)

• Pregnancy (women of childbearing potential must have a negative pregnancy test at study entry and effective contraception)

• Breast-feeding

• History of hypersensitivity to the study drug or to drugs with a similar chemical structure or to insulin glargine

• Treatment with systemic corticosteroids, irrespective of the dose of administration and irrespective of the prior or foreseeable treatment duration

• Treatment with any investigational product in the last 2 months before study entry, except for insulin glargine

• 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 ALT and/or AST greater than three times the upper limit of normal at study entry

• Impaired renal function as shown by serum creatinine >135 µmol/l in men and > 110 µmol/l in women at study entry

• History of drug or alcohol abuse

• Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study

• Subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

• Subject deprived of freedom by a judicial or administrative decision

• Subject is the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Insulin Glargine
One daily injection in the evening. 100 U/ml
• Insulin Glulisine
Given immediately before each of the three main meals. 100 U/ml
• Metformin
At same dosages as the previous treatment
• insulin secretagogue
sulfonylurea or glinide

Locations

Country	Name	City	State
Belgium	Sanofi-Aventis	Brussels
France	Sanofi-Aventis	Paris
Germany	Sanofi-Aventis	Berlin
Greece	Sanofi-Aventis	Athens
Hungary	Sanofi-Aventis	Budapest
Ireland	Sanofi-Aventis	Dublin
Italy	Sanofi-Aventis	Milan
Korea, Republic of	Sanofi-Aventis	Seoul
Lithuania	Sanofi-Aventis	Vilnius
Mexico	Sanofi-Aventis	Mexico
Netherlands	Sanofi-Aventis	Gouda
Poland	Sanofi-Aventis	Warsaw
Russian Federation	Sanofi-Aventis	Moscow
Spain	Sanofi-Aventis	Barcelona
Sweden	Sanofi-Aventis	Stockholm
Taiwan	Sanofi-Aventis	Taipei
Turkey	Sanofi-Aventis	Istanbul
United Kingdom	Sanofi-Aventis	Guildford

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Korea, Republic of,  Lithuania,  Mexico,  Netherlands,  Poland,  Russian Federation,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c		From the beginning to the end of the study	No
Primary	24-hour blood glucose levels		From the beginning to the end of the study	No
Primary	symptomatic hypoglycemia (diurnal and nocturnal)		From the beginning to the end of the study	No
Primary	Severe hypoglycemia (diurnal and nocturnal),		From the beginning to the end of the study	No
Primary	Insulin doses		From the beginning to the end of the study	No
Secondary	Vital signs		From the beginning to the end of the study	No
Secondary	Adverse events		From the beginning to the end of the study	Yes