A Study to Compare Pharmacokinetics (PK) and Pharmacodynamics (PD) of SAR341402 to Insulin Aspart in Subjects With Type 1 Diabetes Mellitus

A Randomized, Double-Blind, Controlled, Single-Dose, 3-Treatment, 3-Period, 6-Sequence Crossover Study to Compare Exposure and Activity of SAR341402 to NovoRapid® and NovoLog® Using the Euglycemic Clamp Technique, in Subjects With Type 1 Diabetes Mellitus

Primary Objective:

To compare exposure and activity of SAR341402 to NovoRapid® and NovoLog®.

Secondary Objective:

To assess the safety and tolerability of SAR341402.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: SAR341402; Drug: Insulin Aspart

Detailed Description

The total study duration for a screened subject will be about 3 - 8 weeks (excluding screening of 2 to 28 days), treatment period of 2 days for each 3 periods (1 overnight stay), a washout period of 5-18 days (preferentially 7 days between consecutive dosing), and an end-of-study visit of 1 day between Days 5 and 14 after the last administration of the investigational product.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany
    • Investigational Site 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 with diabetes mellitus type 1 for more than one year.
• Total insulin dose of < 1.2 U/kg/day.
• Fasting negative serum C-peptide (< 0.3 nmol/L).
• Glycohemoglobin (HbA1c) ≤ 9%.
• 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 musculo-skeletal system), vital signs, electrocardiogram (ECG) and safety lab.

Exclusion criteria:

• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic (apart from diabetes mellitus type 1), hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness.
• More than one episode of severe hypoglycemia with seizure, coma or requiring assistance of another person during the past 6 months.
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (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.
• 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 the medication, with the exception of insulins, 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.
• Positive result on 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test (T); SAR341402: single dose injection	Drug: SAR341402; Pharmaceutical form: solution Route of administration: subcutaneous
Active Comparator: Reference 1 (R1); NovoRapid®: single dose injection	Drug: Insulin Aspart; Pharmaceutical form: solution Route of administration: subcutaneous; Other Names: NovoLog®
Active Comparator: Reference 2 (R2); NovoLog®: single dose injection	Drug: Insulin Aspart; Pharmaceutical form: solution Route of administration: subcutaneous; Other Names: NovoLog®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of PK parameters: maximum plasma concentration (Cmax)	Maximum plasma concentration (Cmax) of SAR341402, NovoRapid and NovoLog within 12 hours	12 hours
Assessment of PK parameters: Area under the concentration versus time curve (AUC)	INS-AUC of SAR341402, NovoRapid, and NovoLog from 0 to 12 hours	12 hours
Assessment of PK parameter: AUC from dosing to last concentration (AUClast)	INS-AUClast is AUC from the time of dosing to the last measurable concentration of SAR341402, NovoRapid, and NovoLog from 0 to 12 hours	12 hours
Assessment of PD parameters: Area under the body weight standardized glucose infusion rate (GIR)	Area under the body weight standardized glucose infusion rate (GIR) versus time curve from 0 to 12 hours post administration (GIR-AUC0-12)	12 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of PK: Fractional area under the concentration versus time curve	INS-AUC0-2 and INS-AUC4-tlast	12 hours
Assessment of PK: Time to 20 % of INS-AUC	Time to 20% of AUC (t20%-INS-AUC) within 12 hours	12 hours
Assessment of PK: time to reach INS-Cmax (INS-tmax)	INS-tmax within 12 hours	12 hours
Assessment of PK: time to reach INS-t1/2z (INS-t1/2z)	INS-t1/2z within 12 hours	12 hours
Assessment of PD: Fractional area under the body weight standardized GIR versus time curve	GIR-AUC0-2 and GIR-AUC4-12	12 hours
Assessment of PD: Time to 20 % of total GIR-AUC0-12h	Time to 20% of total GIR-AUC0-12h (t20%-GIR-AUC0-12h) within 12 hours	12 hours
Assessment of PD: Maximum smoothed body weight standardized GIR (GIRmax)	Maximum smoothed body weight standardized GIR (GIRmax) within 12 hours	12 hours
Assessment of PD: Time to GIRmax (GIR-tmax)	Time to GIRmax (GIR-tmax) within 12 hours	12 hours
Number of adverse events (AEs)	Number of patients with treatment emergent AEs and serious adverse events (SAEs)	8 weeks

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Kapitza C, Nosek L, Schmider W, Teichert L, Nowotny I. Single-Dose Euglycemic Clamp Study Demonstrating Pharmacokinetic and Pharmacodynamic Similarity Between SAR341402 Insulin Aspart and US- and EU-Approved Versions of Insulin Aspart in Subjects with Type 1 Diabetes. Diabetes Technol Ther. 2020 Apr;22(4):278-284. doi: 10.1089/dia.2019.0351. Epub 2019 Dec 30.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2012
• Primary Completion (Actual): December 28, 2012
• Study Completion (Actual): December 28, 2012

Study Registration Dates

• First Submitted: June 27, 2017
• First Submitted That Met QC Criteria: June 27, 2017
• First Posted (Actual): June 29, 2017

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 Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination
• Other Study ID Numbers: PDY12695; 2012-002355-42 (EudraCT Number); U1111-1127-2950 (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