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

NCT02910518 | Completed Phase 1

• 3 other identifiers: BEQ139412016-001498-34U1111-1183-8636
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Type1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• Assessment of PK parameter: maximum observed insulin concentration

  10 hours

• Assessment of PK parameter: area under the concentration time curve

  10 hours

Secondary Outcomes (7)

• Assessment of PK parameter: time to reach Cmax (INS-tmax)

  10 hours

• Assessment of PK parameter: terminal half-life (INS-t1/2z)

  10 hours

• Assessment of PD parameter: area under the body weight standardized glucose infusion rate (GIR) versus time curve from 0 to 10 hours (GIR-AUC0-10)

  10 hours

• Assessment of PD parameter: maximum smoothed body weight standardized GIR (GIRmax)

  10 hours

• Assessment of PD parameter: time to GIRmax (GIR-tmax)

  10 hours

Study Arms (2)

Insulin glulisine (U300) - Test formulation

EXPERIMENTAL

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.

Drug: Insulin glulisine (U300); Drug: Insulin aspart; Drug: NPH insulin; Drug: Glucagon; Drug: Glucose; Drug: Heparin

Insulin glulisine - Reference formulation

ACTIVE COMPARATOR

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.

Drug: Insulin glulisine; Drug: Insulin aspart; Drug: NPH insulin; Drug: Glucagon; Drug: Glucose; Drug: Heparin

Interventions

Insulin glulisine (U300) DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

Also known as: HMR1964 (U300)

Insulin glulisine (U300) - Test formulation

Insulin glulisine DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

Also known as: Apidra®

Insulin glulisine - Reference formulation

Insulin aspart DRUG

Pharmaceutical form: solution Route of administration: intravenous/subcutaneous

Also known as: NovoRapid®

Insulin glulisine (U300) - Test formulation; Insulin glulisine - Reference formulation

NPH insulin DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

Also known as: Insuman® Basal Solostar®

Insulin glulisine (U300) - Test formulation; Insulin glulisine - Reference formulation

Glucagon DRUG

Pharmaceutical form: Powder and solvent for solution for injection Route of administration: subcutaneous

Also known as: GlucaGen® HypoKit

Insulin glulisine (U300) - Test formulation; Insulin glulisine - Reference formulation

Glucose DRUG

Pharmaceutical form: solution Route of administration: intravenous

Also known as: Glucose 20%

Insulin glulisine (U300) - Test formulation; Insulin glulisine - Reference formulation

Heparin DRUG

Pharmaceutical form: solution Route of administration: intravenous

Also known as: Heparin-Natrium-5000

Insulin glulisine (U300) - Test formulation; Insulin glulisine - Reference formulation

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Investigational Site Number 276001

Neuss, 41460, Germany

Location

MeSH Terms

Interventions

insulin glulisine; Insulin Aspart; Insulin, Isophane; Glucagon; Glucose; Heparin

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Long-Acting; Proglucagon; Hexoses; Monosaccharides; Sugars; Carbohydrates; Glycosaminoglycans; Polysaccharides

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2016
• First Posted: September 22, 2016
• Study Start: February 17, 2017
• Primary Completion: May 3, 2017
• Study Completion: May 3, 2017
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)