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

Condition(s) targeted: Type 1 Diabetes Mellitus

Intervention: insulin glargine U200 HOE901 (Drug); insulin glargine U500 HOE901 (Drug); insulin glargine U100 HOE901 (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Sanofi

Official(s) and/or principal investigator(s):
Clinical Sciences & Operations, Study Director, Affiliation: Sanofi

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.

Official title: 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

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Primary outcome: Area under the serum insulin glargine (INS) concentration curve over the first 12 hours after dosing

Secondary outcome:

INS-Area Under the Curve (AUC) over 24 and 36 hours after dosing (INS AUC 0-24 and INS AUC 0-36)

AUC up to the last measurable concentration

Time to reach 50% of INS-AUC 0-36

Time to reach INS-Cmax (INS-tmax)

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)

Time to reach 50% of GIR-AUC0-36 (T50%-GIR-AUC0-36)

Maximum smoothed body weight standardized glucose infusion rate (GIRmax) and time to GIRmax (GIR-Tmax)

Duration of blood glucose control (time to elevation of smoothed blood glucose profile above different pre-specific blood glucose levels)

Safety and tolerability (Number of patients with adverse events, clinically significant changes in vital signs, laboratory parameters)

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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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.

Investigational Site Number 276001, Neuss 41460, Germany

Starting date: August 2014
Last updated: December 23, 2014