euglycemic clamp study comparing two new insulin glargine formulations in subjects with type 1 diabetes mellitus

Conditions: Type1 Diabetes

Summary: primary objective: to demonstrate equivalence in exposure to insulin glargine given as test formulation t and reference formulation r in steady state conditions after 6 once-daily subcutaneous (sc) doses secondary objective: * to assess relative pharmacodynamic activity of the insulin glargine test formulation t to the insulin glargine reference formulation r in steady state conditions after 6 once-daily sc doses * to assess the safety and tolerability of the test and reference formulations of two new insulin glargine formulations

total study duration per subject: 29 to 64 days including screening visit duration of each part of the study for one subject: * screening: 3 to 21 days before 1st dosing (day -21 to day -3) * treatment period 1 and 2: 8 days (dosing on 6 days) * washout between last/1st dosing days of the treatment periods: 7-21 days (preferentially 7 days) end-of-study visit: 7-10 days after last dosing

Eligibility criteria:
inclusion criteria : * male or female subjects, between 18 and 64 years of age, inclusive, with diabetes mellitus type 1 for more than one year * total insulin dose of \< 1.2 u/kg/day * minimum usual basal insulin dose ≥ 0.2 u/kg/day * body weight between 50.0 kg and 110.0 kg, body mass index between 18.5 and 30.0 kg/m2 inclusive * fasting negative serum c-peptide (\< 0.3 nmol/l) * glycohemoglobin (hba1c) ≤ 75 mmol/mol \[≤ 9.0%\] * stable insulin regimen for at least 2 months prior to inclusion in study * certified as otherwise healthy for type-1 diabetes mellitus patient * laboratory parameters within the normal range * women of childbearing potential with negative pregnancy test and use of a highly effective contraceptive method or women with confirmed postmenopausal status exclusion criteria: * any history or presence of clinically relevant cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic (apart from diabetes mellitus type 1), hematological, neurological, psychiatric, systemic (affecting the body as a whole), ocular, gynecologic (if female), or infectious disease; any acute infectious disease or signs of acute illness. * more than one episode of severe hypoglycemia with seizure, coma or requiring assistance of another person during the past 6 months * frequent severe headaches and / or migraine, recurrent nausea and / or vomiting (more than twice a month) * symptomatic hypotension (whatever the decrease in blood pressure), or asymptomatic postural hypotension defined by a decrease in systolic blood pressure equal to or greater than 20 mmhg within three minutes when changing from the supine to the standing position * presence or history of a drug allergy or clinically significant allergic disease according to the investigator's judgment * likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol * presence or history of drug or alcohol abuse (alcohol consumption \> 40 grams / day) * if female, pregnancy (defined as positive beta human chorionic gonadotropin test), breast-feeding * known hypersensitivity to insulin glargine or excipients of the study drug * any history or presence of deep leg vein thrombosis or a frequent appearance of deep leg vein thrombosis in first degree relatives (parents, siblings or children) the above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.