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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

Primary Purpose

Type 1 Diabetes

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

SAR341402

Insulin Aspart

SAR341402

About this trial

This is an interventional treatment trial for Type 1 Diabetes

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Investigational Site Number 2760001

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Test (T)

Reference 1 (R1)

Reference 2 (R2)

Reference 3 (R3)

Arm Description

SAR341402 Mix 70/30: single dose injection

NovoLog Mix 70/30: single dose injection

NovoMix30: single dose injection

SAR341402 rapid-acting solution: single dose injection

Outcomes

Primary Outcome Measures

(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

(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

(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

(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

(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

Secondary Outcome Measures

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

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

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

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

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

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

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

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

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

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

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

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

Full Information

NCT ID

NCT03916601

First Posted

April 12, 2019

Last Updated

April 21, 2022

Sponsor

Sanofi

1. Study Identification

Unique Protocol Identification Number

NCT03916601

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

December 13, 2017 (Actual)

Primary Completion Date

March 22, 2018 (Actual)

Study Completion Date

March 22, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

52 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Test (T)

Arm Type

Experimental

Arm Description

SAR341402 Mix 70/30: single dose injection

Arm Title

Reference 1 (R1)

Arm Type

Active Comparator

Arm Description

NovoLog Mix 70/30: single dose injection

Arm Title

Reference 2 (R2)

Arm Type

Active Comparator

Arm Description

NovoMix30: single dose injection

Arm Title

Reference 3 (R3)

Arm Type

Experimental

Arm Description

SAR341402 rapid-acting solution: single dose injection

Intervention Type

Drug

Intervention Name(s)

SAR341402

Intervention Description

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Intervention Type

Drug

Intervention Name(s)

Insulin Aspart

Other Intervention Name(s)

NovoLog Mix 70/30

Intervention Description

Pharmaceutical form: suspension for injection Route of administration: subcutaneous

Intervention Type

Drug

Intervention Name(s)

Insulin Aspart

Other Intervention Name(s)

Novo Mix 30

Intervention Description

Pharmaceutical form: suspension for injection Route of administration: subcutaneous

Intervention Type

Drug

Intervention Name(s)

SAR341402

Intervention Description

Pharmaceutical form: suspension for injection Route of administration: subcutaneous

Primary Outcome Measure Information:

Title

(Cohort 1) Assessment of PK parameter: Maximum insulin concentration (INS-Cmax)

Description

Maximum plasma concentration (Cmax) of SAR341402 Mix 70/30, NovoLog Mix 70/30, NovoMix 30 and SAR341402 within 24 hours

Time Frame

24 hours

Title

(Cohort 1) Assessment of PK parameter: Area under the insulin concentration time curve (INS-AUClast)

Description

INS-AUC of SAR341402 Mix 70/30, NovoLog Mix 70/30, and NovoMix 30 from 0 to 24 hours

Time Frame

0 to 24 hours

Title

(Cohort 2) Assessment of PK parameters: Area under the insulin concentration time curve from 0 to 4 hours post administration (INS-AUC0-4H)

Description

INS-AUC0-4H for SAR341402 Mix 70/30 and SAR341402 rapid acting solution from 0 to 4 hours

Time Frame

0 to 4 hours

Title

(Cohort 2) Area under the insulin concentration time curve from 4 to 12 hours post administration (INS-AUC4-12H)

Description

INS-AUC4-12H for SAR341402 Mix 70/30 and SAR341402 rapid acting solution from 4 to 12 hours

Time Frame

4 to 12 hours

Title

(Cohort 2) Assessment of PK parameter: Maximum insulin concentration (INS-Cmax)

Description

(Cohort 2) Maximum plasma concentration (Cmax) of SAR341402 Mix 70/30 and SAR341402 rapid acting solution within 24 hours

Time Frame

24 hours

Secondary Outcome Measure Information:

Title

Assessment of PK parameter: Area under the insulin concentration time curve from 0 to infinity (INS-AUC)

Description

(Cohort 1) INS-AUC for SAR341402 Mix 70/30, Novolog Mix 70/30 and NovoMix 30 from 0 to 24 hours

Time Frame

0 to 24 hours

Title

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)

Description

(Cohort 1) INS-AUC0-4H, INS-AUC0-24H, INS-AUC4-24H for SAR341402 Mix 70/30, Novolog Mix 70/30 and NovoMix 30

Time Frame

0 to 4 hours, 0 to 24 hours, and 4 to 24 hours

Title

Assessment of PK parameter: Time to INS-Cmax

Description

(Cohort 1) INS-tmax for SAR341402 Mix 70/30, Novolog Mix 70/30, NovoMix 30 and SAR341402 rapid acting solution within 24 hours

Time Frame

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 -

Title

Assessment of PK parameter: Half-life (t1/2)

Description

(Cohort 1) INS-t1/2z for SAR341402 Mix 70/30, Novolog Mix 70/30 and NovoMix 30 within 24 hours

Time Frame

24 hours

Title

Assessment of PD parameter: GIR versus time curve from 0 to 24 hours post administration (GIR-AUC0-24H)

Description

Time Frame

0 to 24 hours

Title

Assessment of PD parameter: Maximum smoothed body weight standardized glucose infusion rate (GIRmax)

Description

(Cohort 1) GIRmax for SAR341402 Mix 70/30, Novolog Mix 70/30, NovoMix 30 and SAR341402 rapid acting solution within 24 hours

Time Frame

24 hours

Title

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

Description

(Cohort 1) GIR-tmax for SAR341402 Mix 70/30, Novolog Mix 70/30, NovoMix 30 and SAR341402 rapid acting solution within 24 hours

Time Frame

24 hours

Title

Assessment of PK parameter: Time to Cmax (INS-tmax)

Description

(Cohort 2) INS-tmax for SAR341402 Mix 70/30 and SAR341402 rapid acting solution within 24 hours

Time Frame

24 hours

Title

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)

Description

(Cohort 2) GIR-AUC0-4H for SAR341402 Mix 70/30 and SAR341402 rapid acting solution from 0 to 4 hours

Time Frame

0 to 4 hours

Title

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)

Description

(Cohort 2) GIR-AUC4-12H for SAR341402 Mix 70/30 and SAR341402 rapid acting solution from 4 to 12 hours

Time Frame

4 to 12 hours

Title

Assessment of PD parameter: Maximum smoothed body weight standardized glucose infusion rate (GIRmax)

Description

(Cohort 2) GIRmax for SAR341402 Mix 70/30, Novolog Mix 70/30, NovoMix 30 and SAR341402 rapid acting solution within 24 hours

Time Frame

24 hours

Title

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

Description

(Cohort 2) GIR-tmax for SAR341402 Mix 70/30, Novolog Mix 70/30, NovoMix 30 and SAR341402 rapid acting solution within 24 hours

Time Frame

24 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Sciences & Operations

Organizational Affiliation

Sanofi

Official's Role

Study Director

Facility Information:

Facility Name

Investigational Site Number 2760001

City

Neuss

ZIP/Postal Code

41460

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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

Citations:

PubMed Identifier

33236518

Citation

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.

Results Reference

result

Learn more about this trial

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

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