Clinical trial NCT03202875: A Study to Compare Pharmacokinetics (PK) and Pharmacodynamics (PD) of SAR341402 to Insulin Aspart in Subjects With Type 1 Diabetes Mellitus
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-06-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Primary Objective:

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

Secondary Objective:

To assess the safety and tolerability of SAR341402.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of PK parameters: maximum plasma concentration (Cmax)
timeFrame: 12 hours
measure: Assessment of PK parameters: Area under the concentration versus time curve (AUC)
timeFrame: 12 hours
measure: Assessment of PK parameter: AUC from dosing to last concentration (AUClast)
timeFrame: 12 hours
measure: Assessment of PD parameters: Area under the body weight standardized glucose infusion rate (GIR)
timeFrame: 12 hours
Secondary outcomes:
measure: Assessment of PK: Fractional area under the concentration versus time curve
timeFrame: 12 hours
measure: Assessment of PK: Time to 20 % of INS-AUC
timeFrame: 12 hours
measure: Assessment of PK: time to reach INS-Cmax (INS-tmax)
timeFrame: 12 hours
measure: Assessment of PK: time to reach INS-t1/2z (INS-t1/2z)
timeFrame: 12 hours
measure: Assessment of PD: Fractional area under the body weight standardized GIR versus time curve
timeFrame: 12 hours
measure: Assessment of PD: Time to 20 % of total GIR-AUC0-12h
timeFrame: 12 hours
measure: Assessment of PD: Maximum smoothed body weight standardized GIR (GIRmax)
timeFrame: 12 hours
measure: Assessment of PD: Time to GIRmax (GIR-tmax)
timeFrame: 12 hours
measure: Number of adverse events (AEs)
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Investigational Site 276001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.