Back to resultsA Study to Compare Pharmacokinetics (PK) and Pharmacodynamics (PD) of SAR341402 to Insulin Aspart in Subjects With Type 1 Diabetes Mellitus
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
SAR341402
Insulin Aspart
Insulin Aspart
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes
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.
Sites / Locations
- Investigational Site 276001
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
Test (T)
Reference 1 (R1)
Reference 2 (R2)
Arm Description
SAR341402: single dose injection
NovoRapid®: single dose injection
NovoLog®: single dose injection
Outcomes
Primary Outcome Measures
Assessment of PK parameters: maximum plasma concentration (Cmax)
Maximum plasma concentration (Cmax) of SAR341402, NovoRapid and NovoLog within 12 hours
Assessment of PK parameters: Area under the concentration versus time curve (AUC)
INS-AUC of SAR341402, NovoRapid, and NovoLog from 0 to 12 hours
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
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)
Secondary Outcome Measures
Assessment of PK: Fractional area under the concentration versus time curve
INS-AUC0-2 and INS-AUC4-tlast
Assessment of PK: Time to 20 % of INS-AUC
Time to 20% of AUC (t20%-INS-AUC) within 12 hours
Assessment of PK: time to reach INS-Cmax (INS-tmax)
INS-tmax within 12 hours
Assessment of PK: time to reach INS-t1/2z (INS-t1/2z)
INS-t1/2z within 12 hours
Assessment of PD: Fractional area under the body weight standardized GIR versus time curve
GIR-AUC0-2 and GIR-AUC4-12
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
Assessment of PD: Maximum smoothed body weight standardized GIR (GIRmax)
Maximum smoothed body weight standardized GIR (GIRmax) within 12 hours
Assessment of PD: Time to GIRmax (GIR-tmax)
Time to GIRmax (GIR-tmax) within 12 hours
Number of adverse events (AEs)
Number of patients with treatment emergent AEs and serious adverse events (SAEs)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03202875
Brief Title
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
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
November 14, 2012 (Actual)
Primary Completion Date
December 28, 2012 (Actual)
Study Completion Date
December 28, 2012 (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
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
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
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Test (T)
Arm Type
Experimental
Arm Description
SAR341402: single dose injection
Arm Title
Reference 1 (R1)
Arm Type
Active Comparator
Arm Description
NovoRapid®: single dose injection
Arm Title
Reference 2 (R2)
Arm Type
Active Comparator
Arm Description
NovoLog®: single dose injection
Intervention Type
Drug
Intervention Name(s)
SAR341402
Intervention Description
Pharmaceutical form: solution
Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
Insulin Aspart
Other Intervention Name(s)
NovoRapid®
Intervention Description
Pharmaceutical form: solution
Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
Insulin Aspart
Other Intervention Name(s)
NovoLog®
Intervention Description
Pharmaceutical form: solution
Route of administration: subcutaneous
Primary Outcome Measure Information:
Title
Assessment of PK parameters: maximum plasma concentration (Cmax)
Description
Maximum plasma concentration (Cmax) of SAR341402, NovoRapid and NovoLog within 12 hours
Time Frame
12 hours
Title
Assessment of PK parameters: Area under the concentration versus time curve (AUC)
Description
INS-AUC of SAR341402, NovoRapid, and NovoLog from 0 to 12 hours
Time Frame
12 hours
Title
Assessment of PK parameter: AUC from dosing to last concentration (AUClast)
Description
INS-AUClast is AUC from the time of dosing to the last measurable concentration of SAR341402, NovoRapid, and NovoLog from 0 to 12 hours
Time Frame
12 hours
Title
Assessment of PD parameters: Area under the body weight standardized glucose infusion rate (GIR)
Description
Area under the body weight standardized glucose infusion rate (GIR) versus time curve from 0 to 12 hours post administration (GIR-AUC0-12)
Time Frame
12 hours
Secondary Outcome Measure Information:
Title
Assessment of PK: Fractional area under the concentration versus time curve
Description
INS-AUC0-2 and INS-AUC4-tlast
Time Frame
12 hours
Title
Assessment of PK: Time to 20 % of INS-AUC
Description
Time to 20% of AUC (t20%-INS-AUC) within 12 hours
Time Frame
12 hours
Title
Assessment of PK: time to reach INS-Cmax (INS-tmax)
Description
INS-tmax within 12 hours
Time Frame
12 hours
Title
Assessment of PK: time to reach INS-t1/2z (INS-t1/2z)
Description
INS-t1/2z within 12 hours
Time Frame
12 hours
Title
Assessment of PD: Fractional area under the body weight standardized GIR versus time curve
Description
GIR-AUC0-2 and GIR-AUC4-12
Time Frame
12 hours
Title
Assessment of PD: Time to 20 % of total GIR-AUC0-12h
Description
Time to 20% of total GIR-AUC0-12h (t20%-GIR-AUC0-12h) within 12 hours
Time Frame
12 hours
Title
Assessment of PD: Maximum smoothed body weight standardized GIR (GIRmax)
Description
Maximum smoothed body weight standardized GIR (GIRmax) within 12 hours
Time Frame
12 hours
Title
Assessment of PD: Time to GIRmax (GIR-tmax)
Description
Time to GIRmax (GIR-tmax) within 12 hours
Time Frame
12 hours
Title
Number of adverse events (AEs)
Description
Number of patients with treatment emergent AEs and serious adverse events (SAEs)
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
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 276001
City
Neuss
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
31825248
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.
Results Reference
derived
Learn more about this trial
A Study to Compare Pharmacokinetics (PK) and Pharmacodynamics (PD) of SAR341402 to Insulin Aspart in Subjects With Type 1 Diabetes Mellitus
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