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

NCT03916601 | Completed Phase 1 FDA Drug

• 3 other identifiers: PDY150842017-002482-22U1111-1197-7984
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (5)

• (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 Outcomes (12)

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

  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)

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

• Assessment of PK parameter: Time to INS-Cmax

  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)

  24 hours

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

  0 to 24 hours

Study Arms (4)

Test (T)

EXPERIMENTAL

SAR341402 Mix 70/30: single dose injection

Drug: SAR341402

Reference 1 (R1)

ACTIVE COMPARATOR

NovoLog Mix 70/30: single dose injection

Drug: Insulin Aspart

Reference 2 (R2)

ACTIVE COMPARATOR

NovoMix30: single dose injection

Drug: Insulin Aspart

Reference 3 (R3)

EXPERIMENTAL

SAR341402 rapid-acting solution: single dose injection

Drug: SAR341402

Interventions

SAR341402 DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Reference 3 (R3)

Insulin Aspart DRUG

Pharmaceutical form: suspension for injection Route of administration: subcutaneous

Also known as: NovoLog Mix 70/30

Reference 1 (R1)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Investigational Site Number 2760001

Neuss, 41460, Germany

Location

Related Publications (1)

• 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.

  PMID: 33236518 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin Aspart; insulin aspart, insulin aspart protamine drug combination 30:70

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

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: April 12, 2019
• First Posted: April 16, 2019
• Study Start: December 13, 2017
• Primary Completion: March 22, 2018
• Study Completion: March 22, 2018
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)