Euglycemic Clamp Dose-response Study Comparing a New Insulin Glargine Formulation With Lantus®

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

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.