Single Dose Clamp Study To Compare Concentration/Time Profile And Metabolic Activity Profile Of 2 New Formulations Of Insulin Glargine With Lantus

Study Overview
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Brief Summary
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Primary Objective: To compare the pharmacokinetic (PK) characteristics of single doses of insulin glargine given as U200 and U500 with those of a single dose (SD) of Lantus® U100 in a euglycemic clamp setting in subjects with type 1 diabetes. Secondary Objectives: To compare the metabolic activity characteristics of single doses of insulin glargine given as U200 and U500 with those of a single dose of Lantus® U100 in a euglycemic clamp setting in subjects with type 1 diabetes. To assess the safety and tolerability of single doses of U200, U500 and Lantus® U100 in subjects with type 1 diabetes.

Detailed Description
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Total study duration for each subject is between 3.5 and 12 weeks. Two overnight stays at the unit in each of 3 treatment periods.

Official Title
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A Single-Center, Randomized, Double-Blind, 3-Treatment, 3-Period, 6-Sequence Cross-Over Study To Compare The Pharmacokinetic And Pharmacodynamic Effects of Single Doses of Insulin Glargine Given As U200 And U500 To Lantus® In A Euglycemic Clamp Setting In Subjects With Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: insulin glargine U200 HOE901
* Drug: insulin glargine U500 HOE901
* Drug: insulin glargine U100 HOE901


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female subjects, between 18 and 65 years of age, inclusive, with type 1 diabetes mellitus for more than one year, as defined by the American Diabetes Association. Total insulin dose <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. Women of childbearing potential with negative pregnancy test and use of a highly effective contraceptive method or women with confirmed postmenopausal status. Having given written informed consent prior to undertaking any study-related procedure. Exclusion criteria: 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). Presence or history of a drug allergy or clinically significant allergic disease according to the Investigator's judgment. Presence or history of drug or alcohol abuse (alcohol consumption >40 grams / day). Smoking more than 5 cigarettes or equivalent per day, unable to refrain from smoking. 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 in the last month before study start with the exception of insulin products, 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; any biologics (antibody or its derivatives) given within 4 months before randomization. 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: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: insulin glargine U100<br>1 single dose | Drug: insulin glargine U100 HOE901<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous<br>* Other names: Lantus;|
| Experimental: insulin glargine U200<br>1 single dose | Drug: insulin glargine U200 HOE901<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous<br>|
| Experimental: insulin glargine U500<br>1 single dose | Drug: insulin glargine U500 HOE901<br>* Pharmaceutical form:solution for injection 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 glargine (INS) concentration curve over the first 12 hours after dosing |  | 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| INS-Area Under the Curve (AUC) over 24 and 36 hours after dosing (INS AUC 0-24 and INS AUC 0-36) |  | 36 hours | 
| AUC up to the last measurable concentration |  | 36 hours | 
| Time to reach 50% of INS-AUC 0-36 |  | 36 hours | 
| Time to reach INS-Cmax (INS-tmax) |  | 36 hours | 
| Area under the body-weight-standardized Glucose Infusion Rate (GIR) over the first 12, 24 and 36 hours after dosing (GIR-AUC0-12, GIR-AUC0-24 and, GIR-AUC0-36) |  | 36 hours | 
| Time to reach 50% of GIR-AUC0-36 (T50%-GIR-AUC0-36) |  | 36 hours | 
| Maximum smoothed body weight standardized glucose infusion rate (GIRmax) and time to GIRmax (GIR-Tmax) |  | 36 hours | 
| Duration of blood glucose control (time to elevation of smoothed blood glucose profile above different pre-specific blood glucose levels) |  | 4 days | 
| Safety and tolerability (Number of patients with adverse events, clinically significant changes in vital signs, laboratory parameters) |  | 4 days |