A Study to Demonstrate Bioequivalence Between Insulin Glulisine U300 and Insulin Glulisine U100 After a Single Subcutaneous Dose Using the Euglycemic Clamp Technique, in Patients With Type 1 Diabetes Mellitus

NCT ID: NCT02910518

Last Updated: 2022-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-17
• Study Completion Date: 2017-05-03

Brief Summary

Primary Objective:

To demonstrate bioequivalence between insulin glulisine given as 300 Units/mL test formulation and insulin glulisine 100 Units/mL reference formulation after a single subcutaneous (SC) dose.

Secondary Objectives:

• To assess the pharmacodynamic (PD) profiles and further pharmacokinetic (PK) characteristics of insulin glulisine U300 in comparison to insulin glulisine U100 after a single SC dose.
• To assess safety and tolerability of the test and the reference formulation of insulin glulisine.

Detailed Description

The study duration per patient will be 18 to 62 days and will consist of a 4 to 28 days of screening period, a treatment period of 2 days, a washout between dosing occasions of 5-18 days, and follow up visit 7-14 days after last dosing.

Conditions

Type1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Insulin glulisine (U300) - Test formulation

Insulin glulisine (U300) will be given as a single subcutaneous (SC) dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.

Group Type: EXPERIMENTAL

Insulin glulisine (U300)

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: subcutaneous

Insulin aspart

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: intravenous/subcutaneous

NPH insulin

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: subcutaneous

Glucagon

Intervention Type: DRUG

Pharmaceutical form: Powder and solvent for solution for injection

Route of administration: subcutaneous

Glucose

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: intravenous

Heparin

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: intravenous

Insulin glulisine - Reference formulation

Insulin glulisine (U100) will be given as a single SC dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.

Group Type: ACTIVE_COMPARATOR

Insulin glulisine

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: subcutaneous

Insulin aspart

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: intravenous/subcutaneous

NPH insulin

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: subcutaneous

Glucagon

Intervention Type: DRUG

Pharmaceutical form: Powder and solvent for solution for injection

Route of administration: subcutaneous

Glucose

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: intravenous

Heparin

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: intravenous

Interventions

Insulin glulisine (U300)

Pharmaceutical form: solution

Route of administration: subcutaneous

Intervention Type: DRUG

Insulin glulisine

Pharmaceutical form: solution

Route of administration: subcutaneous

Intervention Type: DRUG

Insulin aspart

Pharmaceutical form: solution

Route of administration: intravenous/subcutaneous

Intervention Type: DRUG

NPH insulin

Pharmaceutical form: solution

Route of administration: subcutaneous

Intervention Type: DRUG

Glucagon

Pharmaceutical form: Powder and solvent for solution for injection

Route of administration: subcutaneous

Intervention Type: DRUG

Glucose

Pharmaceutical form: solution

Route of administration: intravenous

Intervention Type: DRUG

Heparin

Pharmaceutical form: solution

Route of administration: intravenous

Intervention Type: DRUG

Other Intervention Names

HMR1964 (U300); Apidra®; NovoRapid®; Insuman® Basal Solostar®; GlucaGen® HypoKit; Glucose 20%; Heparin-Natrium-5000

Eligibility Criteria

Inclusion Criteria

• Male or female subjects with type 1 diabetes mellitus (T1DM) for more than 1 year.
• Total insulin dose of <1.2 U/kg/day.
• Fasting negative serum C-peptide (<0.30 nmol/L).
• Glycohemoglobin at screening (HbA1c) ≤9%.
• Subjects with anti-insulin antibody titer at screening ≤30.0 kU/L.
• Stable insulin regimen for at least 2 months prior to study.
• Normal findings in medical history and physical examination (cardiovascular system, chest and lungs, thyroid, abdomen, nervous system, skin and mucosae, and musculoskeletal system), vital signs, electrocardiogram (ECG), and safety laboratory.

Exclusion Criteria

• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic (apart from T1DM), 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 or any history or presence of heparin induced thrombocytopenia Type II (HIT-type II).
• Severe hypoglycemia resulting in coma/seizures or requiring assistance of another person, and/or hospitalization for diabetic ketoacidosis in the last 6 months before screening visit.
• 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 drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
• Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol.
• Any medication (including medicine containing St John's Wort) within 14 days before inclusion (for systemic glucocorticoids within 3 months) or within 5 times the elimination half-life or PD half-life of the medication, with the exception of insulin, stable treatment (at least 2 months) with thyroid hormones, lipid-lowering and antihypertensive drugs and if female with the exception of hormonal contraception or menopausal hormone replacement therapy.
• Positive reaction to any of the following tests: hepatitis B surface (HBs Ag) antigen, anti hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 276001

Neuss, , Germany

Countries

Germany

Other Identifiers

2016-001498-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1183-8636

Identifier Type: OTHER

Identifier Source: secondary_id

BEQ13941

Identifier Type: -

Identifier Source: org_study_id