Comparison of Exposure and Activity of SAR341402 Mix 70/30 to NovoLog Mix 70/30, NovoMix 30 and SAR341402 Rapid-acting Solution in Patients With Type 1 Diabetes Mellitus

A Randomized, Double-blind, Single-dose, Cross-over Study in Two Cohorts to Compare Exposure and Activity of SAR341402 Mix 70/30 to Novolog® Mix 70/30, Novomix® 30 and SAR341402 Rapid-Acting Solution Using the Euglycemic Clamp Technique, in Patients With Type 1 Diabetes Mellitus

Primary Objectives:

• To demonstrate similarity in exposure of SAR341402 Mix 70/30 to NovoLog Mix 70/30 and NovoMix 30 (cohort 1).
• To demonstrate distinctiveness in early and intermediate exposure of SAR341402 Mix 70/30 compared to SAR341402 rapid-acting solution (cohort 2).

Secondary Objectives:

• To demonstrate similarity in activity of SAR341402 Mix 70/30 to NovoLog Mix 70/30 and NovoMix 30.
• To demonstrate distinctiveness in early and intermediate activity of SAR341402 Mix 70/30 compared to SAR341402 rapid-acting solution.
• To assess the safety and tolerability of SAR341402 rapid-acting solution and SAR341402 Mix 70/30.

Study Overview

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

Detailed Description

• Cohort 1: The total study duration for a screened patient will be about 3 - 8 weeks (excluding screening), with screening period of 4 to 28 days, 3 treatment periods of 2 days each period, washout period of 5 to 18 days, and end-of-study visit at 5 to 12 days after last IMP administration.
• Cohort 2: The total study duration for a screened patient will be about 2 - 5 weeks (excluding screening), with screening period of 4 to 28 days, 2 treatment periods of 2 days each period, washout period of 5 to 18 days, and end-of-study visit at 5 to 12 days after last IMP administration.

• Study Type: Interventional
• Enrollment (Actual): 52
• 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 :

• Total insulin dose of < 1.0 U/kg/day.
• Total basal insulin dose ≤0.4 U/kg/day.
• Fasting serum C-peptide < 0.3 nmol/L.
• Anti-insulin antibody titer ≤30.0 kU/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 and/or hospitalized for diabetic ketoacidosis.
• 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 ≥30 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.
• 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test (T); SAR341402 Mix 70/30: single dose injection	Drug: SAR341402; Pharmaceutical form: solution for injection Route of administration: subcutaneous; Drug: SAR341402; Pharmaceutical form: suspension for injection Route of administration: subcutaneous
Active Comparator: Reference 1 (R1); NovoLog Mix 70/30: single dose injection	Drug: Insulin Aspart; Pharmaceutical form: suspension for injection Route of administration: subcutaneous; Other Names: Novo Mix 30
Active Comparator: Reference 2 (R2); NovoMix30: single dose injection	Drug: Insulin Aspart; Pharmaceutical form: suspension for injection Route of administration: subcutaneous; Other Names: Novo Mix 30
Experimental: Reference 3 (R3); SAR341402 rapid-acting solution: single dose injection	Drug: SAR341402; Pharmaceutical form: solution for injection Route of administration: subcutaneous; Drug: SAR341402; Pharmaceutical form: suspension for injection Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Cohort 1) Assessment of PK parameter: Maximum insulin concentration (INS-Cmax)	Maximum plasma concentration (Cmax) of SAR341402 Mix 70/30, NovoLog Mix 70/30, NovoMix 30 and SAR341402 within 24 hours	24 hours
(Cohort 1) Assessment of PK parameter: Area under the insulin concentration time curve (INS-AUClast)	INS-AUC of SAR341402 Mix 70/30, NovoLog Mix 70/30, and NovoMix 30 from 0 to 24 hours	0 to 24 hours
(Cohort 2) Assessment of PK parameters: Area under the insulin concentration time curve from 0 to 4 hours post administration (INS-AUC0-4H)	INS-AUC0-4H for SAR341402 Mix 70/30 and SAR341402 rapid acting solution from 0 to 4 hours	0 to 4 hours
(Cohort 2) Area under the insulin concentration time curve from 4 to 12 hours post administration (INS-AUC4-12H)	INS-AUC4-12H for SAR341402 Mix 70/30 and SAR341402 rapid acting solution from 4 to 12 hours	4 to 12 hours
(Cohort 2) Assessment of PK parameter: Maximum insulin concentration (INS-Cmax)	(Cohort 2) Maximum plasma concentration (Cmax) of SAR341402 Mix 70/30 and SAR341402 rapid acting solution within 24 hours	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of PK parameter: Area under the insulin concentration time curve from 0 to infinity (INS-AUC)	(Cohort 1) INS-AUC for SAR341402 Mix 70/30, Novolog Mix 70/30 and NovoMix 30 from 0 to 24 hours	0 to 24 hours
Assessment of PK parameter: Area under the insulin concentration time curve for fractional periods post administration (INS-AUC0-4H, INS-AUC0-24H, INS-AUC4-24H)	(Cohort 1) INS-AUC0-4H, INS-AUC0-24H, INS-AUC4-24H for SAR341402 Mix 70/30, Novolog Mix 70/30 and NovoMix 30	0 to 4 hours, 0 to 24 hours, and 4 to 24 hours
Assessment of PK parameter: Time to INS-Cmax	(Cohort 1) INS-tmax for SAR341402 Mix 70/30, Novolog Mix 70/30, NovoMix 30 and SAR341402 rapid acting solution within 24 hours	24 hours - 4. 24 hours - 5. 0 to 24 hours - 6. 24 hours - 7. 24 hours - 8. 24 hours - 9. 0 to 4 hours - 10. 4 to 12 hours - 11. 24 hours - 12. 24 hours -
Assessment of PK parameter: Half-life (t1/2)	(Cohort 1) INS-t1/2z for SAR341402 Mix 70/30, Novolog Mix 70/30 and NovoMix 30 within 24 hours	24 hours
Assessment of PD parameter: GIR versus time curve from 0 to 24 hours post administration (GIR-AUC0-24H)	(Cohort 1) The area under the body weight standardized glucose infusion rate (GIR) versus time curve from 0 to 24 hours post administration for SAR341402 Mix 70/30, Novolog Mix 70/30 and NovoMix 30 from 0 to 24 hours	0 to 24 hours
Assessment of PD parameter: Maximum smoothed body weight standardized glucose infusion rate (GIRmax)	(Cohort 1) GIRmax for SAR341402 Mix 70/30, Novolog Mix 70/30, NovoMix 30 and SAR341402 rapid acting solution within 24 hours	24 hours
Assessment of PD parameter: Time to GIRmax (GIR-tmax)	(Cohort 1) GIR-tmax for SAR341402 Mix 70/30, Novolog Mix 70/30, NovoMix 30 and SAR341402 rapid acting solution within 24 hours	24 hours
Assessment of PK parameter: Time to Cmax (INS-tmax)	(Cohort 2) INS-tmax for SAR341402 Mix 70/30 and SAR341402 rapid acting solution within 24 hours	24 hours
Assessment of PD parameter: The area under the body weight standardized glucose infusion rate (GIR) versus time curve from 0 to 4 hours post administration (GIR-AUC0-4H)	(Cohort 2) GIR-AUC0-4H for SAR341402 Mix 70/30 and SAR341402 rapid acting solution from 0 to 4 hours	0 to 4 hours
Assessment of PD parameter: The area under the body weight standardized glucose infusion rate (GIR) versus time curve from 4 to 12 hours post administration (GIR-AUC4-12H)	(Cohort 2) GIR-AUC4-12H for SAR341402 Mix 70/30 and SAR341402 rapid acting solution from 4 to 12 hours	4 to 12 hours
Assessment of PD parameter: Maximum smoothed body weight standardized glucose infusion rate (GIRmax)	(Cohort 2) GIRmax for SAR341402 Mix 70/30, Novolog Mix 70/30, NovoMix 30 and SAR341402 rapid acting solution within 24 hours	24 hours
Assessment of PD parameter: Time to GIRmax (GIR-tmax)	(Cohort 2) GIR-tmax for SAR341402 Mix 70/30, Novolog Mix 70/30, NovoMix 30 and SAR341402 rapid acting solution within 24 hours	24 hours

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Kapitza C, Nosek L, Schmider W, Teichert L, Mukherjee B, Nowotny I. A single-dose euglycaemic clamp study in two cohorts to compare the exposure of SAR341402 (insulin aspart) Mix 70/30 with US- and European-approved versions of insulin aspart Mix 70/30 and SAR341402 rapid-acting solution in subjects with type 1 diabetes. Diabetes Obes Metab. 2021 Mar;23(3):674-681. doi: 10.1111/dom.14260. Epub 2020 Dec 10.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2017
• Primary Completion (Actual): March 22, 2018
• Study Completion (Actual): March 22, 2018

Study Registration Dates

• First Submitted: April 12, 2019
• First Submitted That Met QC Criteria: April 12, 2019
• First Posted (Actual): April 16, 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 Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination
• Other Study ID Numbers: PDY15084; 2017-002482-22; U1111-1197-7984 (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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes