Clinical trial NCT03916601: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-04-16
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: (Cohort 1) Assessment of PK parameter: Maximum insulin concentration (INS-Cmax)
timeFrame: 24 hours
measure: (Cohort 1) Assessment of PK parameter: Area under the insulin concentration time curve (INS-AUClast)
timeFrame: 0 to 24 hours
measure: (Cohort 2) Assessment of PK parameters: Area under the insulin concentration time curve from 0 to 4 hours post administration (INS-AUC0-4H)
timeFrame: 0 to 4 hours
measure: (Cohort 2) Area under the insulin concentration time curve from 4 to 12 hours post administration (INS-AUC4-12H)
timeFrame: 4 to 12 hours
measure: (Cohort 2) Assessment of PK parameter: Maximum insulin concentration (INS-Cmax)
timeFrame: 24 hours
Secondary outcomes:
measure: Assessment of PK parameter: Area under the insulin concentration time curve from 0 to infinity (INS-AUC)
timeFrame: 0 to 24 hours
measure: 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)
timeFrame: 0 to 4 hours, 0 to 24 hours, and 4 to 24 hours
measure: Assessment of PK parameter: Time to INS-Cmax
timeFrame: 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 -
measure: Assessment of PK parameter: Half-life (t1/2)
timeFrame: 24 hours
measure: Assessment of PD parameter: GIR versus time curve from 0 to 24 hours post administration (GIR-AUC0-24H)
timeFrame: 0 to 24 hours
measure: Assessment of PD parameter: Maximum smoothed body weight standardized glucose infusion rate (GIRmax)
timeFrame: 24 hours
measure: Assessment of PD parameter: Time to GIRmax (GIR-tmax)
timeFrame: 24 hours
measure: Assessment of PK parameter: Time to Cmax (INS-tmax)
timeFrame: 24 hours
measure: 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)
timeFrame: 0 to 4 hours
measure: 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)
timeFrame: 4 to 12 hours
measure: Assessment of PD parameter: Maximum smoothed body weight standardized glucose infusion rate (GIRmax)
timeFrame: 24 hours
measure: Assessment of PD parameter: Time to GIRmax (GIR-tmax)
timeFrame: 24 hours
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Investigational Site Number 2760001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
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.