Phase III Study for Glimepiride + Metformin Hydrochloride (Amaryl M) Slow Release (SR)

A 16-Week Controlled, Double Blind, Double Dummy, Randomized, Two Arm Parallel-Group Study to Compare the Efficacy and Safety of Amaryl M 1/250 mg b.i.d vs. Amaryl M SR 2/500 mg od. in Patients With Type 2 Diabetes Mellitus

Primary:

To show the equivalence in terms of efficacy glycated hemoglobin (HbA1c) of glimepiride/metformin slow-release combination tablet (Amaryl M SR 2/500) once daily compared with fixed-dose glimepiride/metformin combination tablet (Amaryl M 1/250) twice a day on HbA1c in patients with type 2 Diabetes Mellitus (DM)

Secondary: To compare the following parameters in two treatment arm

• Efficacy; Fasting Plasma Glucose (FPG) and Post-prandial two hours plasma glucose (PP2h)
• Response rates in terms of HbA1c, FPG
• Patient compliance

Safety:

• episodes of hypoglycemia
• adverse events
• laboratory values including hematology blood chemistry and urinalysis
• vital sign and physical examination

Inclusion Criteria:

• Subjects with type 2 DM diagnosed for at least 3 months but no longer than 10 years before screening;
• - BMI ≤ 40 kg/m²;
• A negative pregnancy test for all females of childbearing potential

Exclusion Criteria:

• A history of acute metabolic complications such as diabetic ketoacidosis or hyperosmolar nonketotic coma within 3 months before screening;
• Current therapy with any oral anti-diabetic drugs or previous use in the 4 weeks other than sulfonylureas or metformin (8 weeks in case of thiazolidinedione) before screening;
• Concomitant treatment prohibited during the study period;
• Any oral anti-diabetic drugs other than study medication
• Any insulin therapy over 7 days consecutively or intermittently in order to treat acute metabolic decompensation or systemic infection during the study
• Intermittent use of systemic corticosteroids or large dose of inhaled steroids
• Subjects with clinically significant renal (serum creatinine level >1.5 mg/dL in male and >1.4 mg/dL in female) or hepatic disease (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2x upper limit of normal (ULN));
• Subjects with acute and severe cardiovascular disease (e.g. heart failure, myocardiac infarction, stroke etc.)
• Clinically significant laboratory abnormality on screening labs or any medical condition that would affect the completion or outcome of the study in the opinion of the investigator and/or sponsor;
• Pregnant or lactating females;
• History of drug or alcohol abuse;
• Subjects with known hypersensitivity to glimepirides, or metformin; Night-shift workers;
• Treatment with any investigational product in the last 3 months before study entry;

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