Clinical trial NCT00174642: Opposing Step-by-step Insulin Reinforcement to Intensified Strategy
Official title: Comparison of Three Therapeutic Strategies for Treating Type 2 Diabetes Mellitus Patients Poorly Controlled With Basal Insulin Associated With Oral Antidiabetic Drugs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 811
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: HbA1c
timeFrame: From the beginning to the end of the study
measure: 24-hour blood glucose levels
timeFrame: From the beginning to the end of the study
measure: symptomatic hypoglycemia (diurnal and nocturnal)
timeFrame: From the beginning to the end of the study
measure: Severe hypoglycemia (diurnal and nocturnal),
timeFrame: From the beginning to the end of the study
measure: Insulin doses
timeFrame: From the beginning to the end of the study
Secondary outcomes:
measure: Vital signs
timeFrame: From the beginning to the end of the study
measure: Adverse events
timeFrame: From the beginning to the end of the study
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Sanofi-Aventis
city: Paris
country: France
facility: Sanofi-Aventis
city: Berlin
country: Germany
facility: Sanofi-Aventis
city: Athens
country: Greece
facility: Sanofi-Aventis
city: Budapest
country: Hungary
facility: Sanofi-Aventis
city: Dublin
country: Ireland
facility: Sanofi-Aventis
city: Milan
country: Italy
facility: Sanofi-Aventis
city: Seoul
country: Korea, Republic of
facility: Sanofi-Aventis
city: Vilnius
country: Lithuania
facility: Sanofi-Aventis
city: Mexico
country: Mexico
facility: Sanofi-Aventis
city: Gouda
country: Netherlands
facility: Sanofi-Aventis
city: Warsaw
country: Poland
facility: Sanofi-Aventis
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis
city: Barcelona
country: Spain
facility: Sanofi-Aventis
city: Stockholm
country: Sweden
facility: Sanofi-Aventis
city: Taipei
country: Taiwan
facility: Sanofi-Aventis
city: Istanbul
country: Turkey
facility: Sanofi-Aventis
city: Guildford
country: United Kingdom
facility: Sanofi-Aventis
Study officials:
affiliation: Sanofi
name: Valérie Pilorget, MD
role: STUDY_DIRECTOR
References: