euglycemic clamp dose-response study comparing a new insulin glargine formulation with lantus®

Conditions: Type 1 Diabetes Mellitus

Summary: primary objective: - to assess the total metabolic effect ratios of a new insulin glargine formulation versus lantus® secondary objectives: * to assess the exposure ratios of a new insulin glargine formulation versus lantus® * to compare the duration of action of a new insulin glargine formulation versus lantus® * to explore the dose response and dose exposure relationship of a new insulin glargine formulation * to assess the safety and tolerability of a new insulin glargine formulation

the study period for one patient is one month in average and it can last up to 11 weeks broken down as follows: * screening: 3 to 28 days * treatment period: 1 to 4 days: 2 days (1 overnight stay) * washout period: 5 to 18 days (preferentially 7 days between consecutive dosings) * end of study: 1 day after the last dosing

Eligibility criteria:
inclusion criteria: * male or female subjects with diabetes mellitus type 1 for more than one year, * total insulin dose of \<1.2 u/kg/day, * glycohemoglobin (hba1c) ≤ 9.0%, * fasting negative serum c-peptide (\< 0.3 nmol/l), * stable insulin regimen for at least 2 months prior to study, * normal findings in medical history and physical examination (cardiovascular system, chest and lungs, thyroid, abdomen, nervous system, skin and mucosae, and musculo-skeletal system), vital signs, electrocardiogram (ecg) and safety lab, * 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 sbp 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, * likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol, * pregnant or breast feeding women, * any medication (including st john's wort) within 14 days before inclusion, or within 5 times the elimination half-life or pharmacodynamic half-life of that drug, whichever the longest and regular use of any medication other than insulins in the last month before study start with the exception of thyroid hormones, lipid-lowering and antihypertensive drugs, and, if female, with the exception of hormonal contraception or menopausal hormone replacement therapy; any vaccination within the last 28 days, * positive reaction to any of the following tests: hepatitis b surface (hbs ag) antigen, antihepatitis b core antibodies (anti-hbc ab) if compound having possible immune activities, anti-hepatitis c virus (anti-hcv2) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-hiv1 and anti hiv2 ab), * known hypersensitivity to insulin glargine and excipients, * any history or presence of deep leg vein thrombosis. the above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.