Euglycemic Clamp Study Comparing Two New Insulin Glargine Formulations in Subjects With Type 1 Diabetes Mellitus

A Double-blind, Randomized, Two-treatment Crossover Bioequivalence Study Comparing Two New Insulin Glargine Formulations Using the Euglycemic Clamp Technique in Subjects With Type 1 Diabetes Mellitus

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

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.