A Study to Compare Pharmacokinetics and Pharmacodynamics of SAR342434 to Insulin Lispro in Subjects With Type 1 Diabetes
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
SAR342434
Insulin Lispro
Insulin Lispro
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.
- Any history or presence of deep leg vein thrombosis or a frequent appearance of deep leg vein thrombosis in 1st degree relatives (parents, siblings or children).
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Sites / Locations
- Sanofi Administrative Office
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
SAR342434: single dose injection
US-approved Humalog®: single dose injection
EU-approved Humalog®: single dose injection
Outcomes
Primary Outcome Measures
Maximum plasma concentration (Cmax) of SAR342434, US-approved Humalog and EU-approved Humalog
Area under the concentration versus time curve (AUC) of SAR342434, US-approved Humalog and EU-approved Humalog
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
The fractional area under the concentration versus time curve from 0 or y to x hours post administration (INS-AUC0 or Y to X)
Time to 20% of AUC (t20%-AUC)
NS-tmax, INS-t1/2z
The fractional area under the body weight standardized GIR versus time curve from 0 or y to x hours post administration (GIR-AUC0 or Y to X)
Time to 20% of total GIR-AUC0-12h (t20%-GIR-AUC0-12h)
Maximum smoothed body weight standardized GIR (GIRmax)
Time to GIRmax (GIR-tmax)
Duration of blood glucose control (time to elevation of smoothed blood glucose profile above clamp level and to elevation above different pre-specified blood glucose levels)
Number of patients with AEs, SAEs, laboratory, vital signs and electrocardiographic abnormalities , injections site reaction assessment (ISR), and if any, hypoglycemia
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02273258
Brief Title
A Study to Compare Pharmacokinetics and Pharmacodynamics of SAR342434 to Insulin Lispro in Subjects With Type 1 Diabetes
Official Title
A Randomized, Double-Blind, Controlled, Single-Dose, 3-Treatment, 3-Period, 6-Sequence Crossover Study to Compare Exposure and Activity of SAR342434 to Humalog® Using the Euglycemic Clamp Technique, in Subjects With Type 1 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Primary Objective:
To compare exposure and activity of SAR342434 to US-approved and EU-approved Humalog®.
Secondary Objective:
To assess the safety and tolerability of SAR342434.
Detailed Description
The total study duration for a screened subject will be about 3 - 8 weeks (min-max duration, excl. screening)
Screening: 2 to 28 days (D -28 to D -2)
Treatment period 1 - 3: 2 days (1 overnight stay)
Washout: 5 - 18 days (preferentially 7 days between consecutive dosing)
End-of-study visit: 1 day between D 5 and D14 after last administration of 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
SAR342434: single dose injection
Arm Title
Reference 1 (R1)
Arm Type
Active Comparator
Arm Description
US-approved Humalog®: single dose injection
Arm Title
Reference 2 (R2)
Arm Type
Active Comparator
Arm Description
EU-approved Humalog®: single dose injection
Intervention Type
Drug
Intervention Name(s)
SAR342434
Intervention Description
Pharmaceutical form:solution Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
Insulin Lispro
Intervention Description
Pharmaceutical form:solution Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
Insulin Lispro
Intervention Description
Pharmaceutical form:solution Route of administration: subcutaneous
Primary Outcome Measure Information:
Title
Maximum plasma concentration (Cmax) of SAR342434, US-approved Humalog and EU-approved Humalog
Time Frame
12 hours
Title
Area under the concentration versus time curve (AUC) of SAR342434, US-approved Humalog and EU-approved Humalog
Time Frame
12 hours
Title
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
The fractional area under the concentration versus time curve from 0 or y to x hours post administration (INS-AUC0 or Y to X)
Time Frame
12 hours
Title
Time to 20% of AUC (t20%-AUC)
Time Frame
12 hours
Title
NS-tmax, INS-t1/2z
Time Frame
12 hours
Title
The fractional area under the body weight standardized GIR versus time curve from 0 or y to x hours post administration (GIR-AUC0 or Y to X)
Time Frame
12 hours
Title
Time to 20% of total GIR-AUC0-12h (t20%-GIR-AUC0-12h)
Time Frame
12 hours
Title
Maximum smoothed body weight standardized GIR (GIRmax)
Time Frame
12 hours
Title
Time to GIRmax (GIR-tmax)
Time Frame
12 hours
Title
Duration of blood glucose control (time to elevation of smoothed blood glucose profile above clamp level and to elevation above different pre-specified blood glucose levels)
Time Frame
12 hours
Title
Number of patients with AEs, SAEs, laboratory, vital signs and electrocardiographic abnormalities , injections site reaction assessment (ISR), and if any, hypoglycemia
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.
Any history or presence of deep leg vein thrombosis or a frequent appearance of deep leg vein thrombosis in 1st degree relatives (parents, siblings or children).
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
Sanofi Administrative Office
City
Frankfurt
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
A Study to Compare Pharmacokinetics and Pharmacodynamics of SAR342434 to Insulin Lispro in Subjects With Type 1 Diabetes
We'll reach out to this number within 24 hrs