A Study to Compare Pharmacokinetics (PK) and Pharmacodynamics (PD) of SAR341402 to Insulin Aspart in Subjects With Type 1 Diabetes Mellitus

Type 1 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03202875
• Other study ID #: PDY12695
• Secondary ID: 2012-002355-42U1
• Status: Completed
• Phase: Phase 1
• Start date: November 14, 2012
• Est. completion date: December 28, 2012

Study information

• Verified date: April 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

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

Secondary Objective:

To assess the safety and tolerability of SAR341402.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 28, 2012
• Est. primary completion date: December 28, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• SAR341402
Pharmaceutical form: solution Route of administration: subcutaneous
• Insulin Aspart
Pharmaceutical form: solution Route of administration: subcutaneous
• Insulin Aspart
Pharmaceutical form: solution Route of administration: subcutaneous

Locations

Country	Name	City	State
Germany	Investigational Site 276001	Neuss

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of PK parameters: maximum plasma concentration (Cmax)	Maximum plasma concentration (Cmax) of SAR341402, NovoRapid and NovoLog within 12 hours	12 hours
Primary	Assessment of PK parameters: Area under the concentration versus time curve (AUC)	INS-AUC of SAR341402, NovoRapid, and NovoLog from 0 to 12 hours	12 hours
Primary	Assessment of PK parameter: AUC from dosing to last concentration (AUClast)	INS-AUClast is AUC from the time of dosing to the last measurable concentration of SAR341402, NovoRapid, and NovoLog from 0 to 12 hours	12 hours
Primary	Assessment of PD parameters: Area under the body weight standardized glucose infusion rate (GIR)	Area under the body weight standardized glucose infusion rate (GIR) versus time curve from 0 to 12 hours post administration (GIR-AUC0-12)	12 hours
Secondary	Assessment of PK: Fractional area under the concentration versus time curve	INS-AUC0-2 and INS-AUC4-tlast	12 hours
Secondary	Assessment of PK: Time to 20 % of INS-AUC	Time to 20% of AUC (t20%-INS-AUC) within 12 hours	12 hours
Secondary	Assessment of PK: time to reach INS-Cmax (INS-tmax)	INS-tmax within 12 hours	12 hours
Secondary	Assessment of PK: time to reach INS-t1/2z (INS-t1/2z)	INS-t1/2z within 12 hours	12 hours
Secondary	Assessment of PD: Fractional area under the body weight standardized GIR versus time curve	GIR-AUC0-2 and GIR-AUC4-12	12 hours
Secondary	Assessment of PD: Time to 20 % of total GIR-AUC0-12h	Time to 20% of total GIR-AUC0-12h (t20%-GIR-AUC0-12h) within 12 hours	12 hours
Secondary	Assessment of PD: Maximum smoothed body weight standardized GIR (GIRmax)	Maximum smoothed body weight standardized GIR (GIRmax) within 12 hours	12 hours
Secondary	Assessment of PD: Time to GIRmax (GIR-tmax)	Time to GIRmax (GIR-tmax) within 12 hours	12 hours
Secondary	Number of adverse events (AEs)	Number of patients with treatment emergent AEs and serious adverse events (SAEs)	8 weeks