A Bioequivalence Study Comparing Two Different Strengths Formulations of Insulin Lispro in Patients With Type 1 Diabetes

A Randomized, Double-blind, Single-dose, 2-treatment, 2-period, 2-sequence Crossover Bioequivalence Study Comparing Two Different Strengths Formulations of Insulin Lispro Using the Euglycemic Clamp Technique, in Patients With Type 1 Diabetes Mellitus

Primary Objective:

To demonstrate bioequivalence between insulin lispro given as SAR342434, 200 Units/ml test formulation (T) and insulin lispro 100 Units/ml reference formulation (R) after a single subcutaneous (SC) dose

Secondary Objectives:

• To assess the pharmacodynamic profiles and further pharmacokinetic characteristics of the test formulation (T) in comparison to the reference formulation (R) after a single SC dose
• To assess the safety and tolerability of the test and the reference formulation of insulin lispro

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Insulin Lispro SAR342434

Detailed Description

Study duration per participant is approximately 62 days including a screening period up to 28 days before first dose, 2 periods of 2 days, a wash out period of 5 to 18 days (preferred7 days) and an end of study visit 7 to 14 days after the last dose

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Investigational Site Number 2760001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Male or female patients, between 18 and 64 years of age, inclusive, with diabetes mellitus type 1 for more than one year
• Total insulin dose of <1.0 U/kg/day
• Fasting serum C-peptide <0.30 nmol/L at screening
• Glycohemoglobin (HbA1c) ≤75 mmol/mol (≤9%) at screening
• Stable insulin regimen for at least 2 months prior to study (day of insulin regimen switch, with respect to safety of the patient and scientific integrity of the study).
• Patients with anti-insulin antibody titer at screening ≤ 30.0 kU/L
• Body weight between 50.0 kg and 100.0 kg, inclusive, il male , and between 40.0 and 90.0 kg, inclusive, if female, Body Mass Index between 18 and 30.0 kg/m², inclusive

Exclusion criteria:

• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness or any history or presence of HIT-type II (heparin induced thrombocytopenia Type II)
• More than 1 episode of 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 headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only, more than twice a month).
• Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥20 mmHg within 3 minutes when changing from supine to 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
• If female, pregnancy (defined as positive β-HCG blood test), breast-feeding

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: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test (T); Insulin Lispro (SAR342434), 200 Units/ml, single dose on day 1 of each period	Drug: Insulin Lispro SAR342434; Pharmaceutical form:solution for injection Route of administration: subcutaneous; Other Names: Insulin lispro Sanofi®
Active Comparator: Reference (R); Insulin Lispro Sanofi® ,100 Units/ml, single dose on day 1 of each period	Drug: Insulin Lispro SAR342434; Pharmaceutical form:solution for injection Route of administration: subcutaneous; Other Names: Insulin lispro Sanofi®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of pharmacokinetc (PK) parameter:INS-Cmax	Maximum Insulin (INS) concentration	10 hours
Assessment of PK parameter :INS-AUClast -	Area under INS concentration time curve from 0 to last measurable concentration -	10 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of PK parameter:INS-AUC	Area under INS concentration time curve from 0 to infinity	10 hours
Assessment of PK parameter:INS-tmax	Time to reach INS-Cmax	10 hours
Assessment of PK parameter:INS-t1/2z	INS terminal half life	10 hours
Assessment of pharmacodynamic (PD) parameter:GIR-AUC0-8	Area under the Glucose Infusion Rate (GIR) time curve from 0 to 8 hours	8 hours
Assessment of PD parameter:GIR-max	Maximum smoothed GIR	8 hours
Assessment of PD parameter:GIR-tmax	Time to reach GIR-max	8 hours
Duration of blood glucose control	Duration of blood glucose control at or below 105 mg/dL	8 hours
Adverse Events	Number of participants with adverse events	Up to Day 62

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2019
• Primary Completion (Actual): August 19, 2019
• Study Completion (Actual): August 19, 2019

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: April 3, 2019
• First Posted (Actual): April 4, 2019

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

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 Lispro
• Other Study ID Numbers: BEQ15846; 2018-003131-30 (EudraCT Number); U1111-1207-8959 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No