Opposing Step-by-step Insulin Reinforcement to Intensified Strategy

Overview[ - collapse ][ - ]

Purpose 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.
ConditionDiabetes Mellitus, Type 2
InterventionDrug: Insulin Glargine
Drug: Insulin Glulisine
Drug: Metformin
Drug: insulin secretagogue
PhasePhase 3
SponsorSanofi
Responsible PartySanofi
ClinicalTrials.gov IdentifierNCT00174642
First ReceivedSeptember 9, 2005
Last UpdatedSeptember 14, 2009
Last verifiedSeptember 2009

Tracking Information[ + expand ][ + ]

First Received DateSeptember 9, 2005
Last Updated DateSeptember 14, 2009
Start DateDecember 2004
Estimated Primary Completion DateNot Provided
Current Primary Outcome Measures
  • HbA1c [Time Frame: From the beginning to the end of the study] [Designated as safety issue: No]
  • 24-hour blood glucose levels [Time Frame: From the beginning to the end of the study] [Designated as safety issue: No]
  • symptomatic hypoglycemia (diurnal and nocturnal) [Time Frame: From the beginning to the end of the study] [Designated as safety issue: No]
  • Severe hypoglycemia (diurnal and nocturnal), [Time Frame: From the beginning to the end of the study] [Designated as safety issue: No]
  • Insulin doses [Time Frame: From the beginning to the end of the study] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • Vital signs [Time Frame: From the beginning to the end of the study] [Designated as safety issue: No]
  • Adverse events [Time Frame: From the beginning to the end of the study] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief TitleOpposing Step-by-step Insulin Reinforcement to Intensified Strategy
Official TitleComparison of Three Therapeutic Strategies for Treating Type 2 Diabetes Mellitus Patients Poorly Controlled With Basal Insulin Associated With Oral Antidiabetic Drugs
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionDiabetes Mellitus, Type 2
InterventionDrug: Insulin Glargine
One daily injection in the evening. 100 U/ml
Drug: Insulin Glulisine
Given immediately before each of the three main meals. 100 U/ml
Drug: Metformin
At same dosages as the previous treatment
Drug: insulin secretagogue
sulfonylurea or glinide
Study Arm (s)
  • Experimental: 1
    Insulin Glargine + 3 bolus of Insulin Glulisine + Metformin
  • Experimental: 2
    Insulin Glargine + 1 to 3 bolus of Insulin Glulisine + Metformin
  • Experimental: 3
    Insulin Glargine + 1 to 3 bolus of Insulin Glulisine + Metformin + Insulin secretagogue

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment811
Estimated Completion DateNot Provided
Estimated Primary Completion DateDecember 2008
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.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesBelgium, France, Germany, Greece, Hungary, Ireland, Italy, Korea, Republic of, Lithuania, Mexico, Netherlands, Poland, Russian Federation, Spain, Sweden, Taiwan, Turkey, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number NCT00174642
Other Study ID NumbersHMR1964A_3506
Has Data Monitoring CommitteeNot Provided
Information Provided BySanofi
Study SponsorSanofi
CollaboratorsNot Provided
Investigators Study Director: Valérie Pilorget, MD Sanofi
Verification DateSeptember 2009

Locations[ + expand ][ + ]

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