Lantus Versus NPH: Comparison in Insulin Naive People Not Adequately Controlled With at Least One Oral Anti Diabetics (OAD) Treatment

Study Overview
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Brief Summary
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Primary Objective: To demonstrate the superiority of insulin glargine over insulin NPH (Neutral Protamin Hagedornon) the change in HbA1c from baseline to the end of the treatment period. Secondary Objective: To compare between treatment groups: Plasma glucose (fasting, nocturnal) over time, Changes from baseline in HbA1c over time, Percentage of patients who reach the target of HbA1c <7 and <6.5, Use of prandial insulin as rescue medication at month 6, Incidence and rate of hypoglycemia (symptomatic diurnal and nocturnal, asymptomatic and severe), Daily dose of insulin, Change in body weight from baseline, Evolution of 8-point plasma-glucose (PG) profiles, Overall safety, Patient reported outcomes (treatment satisfaction).

Official Title
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Superiority of Insulin Glargine Lantus vs. NPH: Treat to Normoglycemia Concept.Effect of Insulin Glargine in Comparison to Insulin NPH in Insulin-nave People With Type 2 Diabetes Mellitus Treated With at Least One OAD and Not Adequately Controlled

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin Glargine (HOE901) [Lantus]
* Drug: Glimepiride
* Drug: human insulin [NPH]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Insulin-naïve type 2 diabetes mellitus Type 2 diabetes mellitus diagnosed for at least 1 year Treated with at least one OAD (Metformin [daily dose of at least 1000mg], Sulfonylurea, glinides or alpha-glucosidase inhibitor) at stable dose for at least 3 months. HbA1c > or = 7.0% and < or = 10.5% BMI < 40 kg/m² Ability and willingness to perform plasma glucose monitoring using the sponsor-provided glucose meter and patient diary at home Informed consent obtained in writing at enrolment into the study Willingness and ability to comply with the study protocol Exclusion criteria: Treatment with GLP-1 agonists or with DPP-IV inhibitors in the 3 months prior to study entry Treatment with TZD as monotherapy Diabetes mellitus other than Type 2 (e.g. secondary to pancreatic disorders, drugs or chemical agents intake...) Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to visit 1, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study (an optic fundus examination should have been performed within the 2 years prior to study entry) Impaired renal function: serum creatinine > or =1.5 mg/dL (> or = 133µmol/L) or > or = 1.4 mg/dL (> or = 124 µmol/L) in men and women, respectively History of sensitivity to the study drugs or to drugs with a similar chemical structure Impaired hepatic function (ALT and/or AST > 3 x upper limit of normal range) Pregnant or lactating women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method), Treatment with systemic corticosteroids within the 3 months prior to study entry or likelihood of requiring treatments during the study which are not permitted. Treatment with an investigational product in the 30 days prior to visit 1 Alcohol or drug abuse in the last year Presence of any condition (medical, psychological, social or geographical), current or anticipated that the Investigator feels would compromise the patient's safety or limit the patient successful participation in the study (including night shift worker) 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
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Before randomization (common with arm 2): 2 weeks of Screening phase: Oral Anti Diabetics (OAD) 2 weeks of Run-In phase: switch of OAD (Sulfonylurea (except Glimepiride), glinides or alpha-glucosidase inhibitor) to Glimepiride After randomization: 36 weeks of study treatment phase: Insulin Glargine + OAD(s) at stable dose | Drug: Insulin Glargine (HOE901) [Lantus]<br>* 100 Units/ml solution for injection in a pre-filled pen SoloStar® (3 ml)<br>Drug: Glimepiride<br>* tablets of 1 and 2 mg<br>|
| Active Comparator: 2<br>Before randomization (common with arm 1): 2 weeks of Screening phase: Oral Anti Diabetics (OAD) 2 weeks of Run-In phase: switch of OAD (Sulfonylurea (except Glimepiride), glinides or alpha-glucosidase inhibitor) to Glimepiride After randomization: 36 weeks of study treatment phase: NPH + OAD(s) at stable dose | Drug: Glimepiride<br>* tablets of 1 and 2 mg<br>Drug: human insulin [NPH]<br>* 100 IU/ml suspension for injection in a prefilled pen OptiSet® (3 ml)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c |  | Recorded at baseline (week 0), week 12, week 24 and week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-monitored fasting plasma glucose (FPG) |  | Before baseline (week 0), weeks 12, 24 and 36 | 
| 8-points profiles |  | The week before baseline, at 12, 24 and 36 weeks | 
| Episodes of hypoglycemia |  | From the week -2 to the week 36 | 
| Daily doses of insulin |  | At week 1, week 2, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 20, week 24, week 28, week 32, week 36 | 
| Need of additional prandial insulin |  | At week 24 |