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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: insulin glargine U100 HOE901; Drug: insulin glargine U200 HOE901; Drug: insulin glargine U500 HOE901

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Investigational Site Number 276001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: insulin glargine U100; 1 single dose	Drug: insulin glargine U100 HOE901; Pharmaceutical form:solution for injection Route of administration: subcutaneous; Other Names: Lantus
Experimental: insulin glargine U200; 1 single dose	Drug: insulin glargine U200 HOE901; Pharmaceutical form:solution for injection Route of administration: subcutaneous
Experimental: insulin glargine U500; 1 single dose	Drug: insulin glargine U500 HOE901; Pharmaceutical form:solution for injection Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: July 24, 2014
• First Submitted That Met QC Criteria: July 24, 2014
• First Posted (Estimate): July 25, 2014

Study Record Updates

• Last Update Posted (Estimate): December 24, 2014
• Last Update Submitted That Met QC Criteria: December 23, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine
• Other Study ID Numbers: PDY13928; 2014-001252-33; U1111-1153-3712 (Other Identifier: UTN)