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

Study Overview
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Brief Summary
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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

Detailed Description
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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

Official Title
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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

Conditions
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Type1 Diabetes

Intervention / Treatment
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* Drug: Insulin glargine new formulation HOE901


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin glargine new formulation (test T formulation)<br>Once daily for 6 days | Drug: Insulin glargine new formulation HOE901<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>|
| Experimental: Insulin glargine new formulation (reference R formulation)<br>Once daily for 6 days | Drug: Insulin glargine new formulation HOE901<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the serum insulin concentration curve within 24 hours (INS-AUC0-24) after dosing on Day 6 |  | 24-hours (D6 to D7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum insulin concentration (INS-Cmax) |  | 24-hours (D6 to D7) | 
| Time to INS-Cmax (INS-tmax) |  | 24-hours (D6 to D7) | 
| Time to reach 50% of INS-AUC0-24 (T50%-INS-AUC0-24) |  | 24-hours (D6 to D7) | 
| Area under the body-weight-standardized Glucose Infusion Rate (GIR) within 24 hours (GIR-AUC0-24h) after dosing on Day 6 during the clamp |  | 24-hours (D6 to D7) | 
| Maximum smoothed body weight standardized glucose infusion rate (GIRmax) |  | 24-hours (D6 to D7) | 
| Time to GIRmax (GIR-Tmax) |  | 24-hours (D6 to D7) | 
| Time to reach at least 50% of GIR-AUC0-24 (T50%-GIR-AUC0-24) |  | 24-hours (D6 to D7) | 
| Duration of blood glucose control (time to elevation of smoothed blood glucose profile above clamp level and to elevation above different prespecified blood glucose levels) |  | 24-hours (D6 to D7) | 
| Safety as measured by adverse events/serious adverse events, ohypoglycemia events, physical examinations, clinical laboratory, electrocardiograms, vital signs, injection site reactions and anti-insulin antibodies. |  | up to 9 weeks |