Type 1 Diabetes Mellitus
Conditions
Brief summary
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
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.
Interventions
DRUGinsulin glargine U200 HOE901
Pharmaceutical form:solution for injection Route of administration: subcutaneous
DRUGinsulin glargine U500 HOE901
Pharmaceutical form:solution for injection Route of administration: subcutaneous
DRUGinsulin glargine U100 HOE901
Pharmaceutical form:solution for injection Route of administration: subcutaneous
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the serum insulin glargine (INS) concentration curve over the first 12 hours after dosing | 12 hours |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| INS-Area Under the Curve (AUC) over 24 and 36 hours after dosing (INS AUC 0-24 and INS AUC 0-36) | 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 |
| Time to reach 50% of GIR-AUC0-36 (T50%-GIR-AUC0-36) | 36 hours |
Countries
Germany
Outcome results
None listed