A Study to Compare Pharmacokinetics and Pharmacodynamics of SAR342434 to Insulin Lispro in Subjects With Type 1 Diabetes

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 SAR342434 to Humalog® Using the Euglycemic Clamp Technique, in Subjects With Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02273258
• Other study ID #: PDY12704
• Secondary ID: 2012-004453-86U1
• Status: Completed
• Phase: Phase 1
• First received: October 21, 2014
• Last updated: October 21, 2014
• Start date: March 2013
• Est. completion date: July 2013

Study information

• Verified date: October 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• 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.

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• SAR342434
Pharmaceutical form:solution Route of administration: subcutaneous
• Insulin Lispro
Pharmaceutical form:solution Route of administration: subcutaneous
• Insulin Lispro
Pharmaceutical form:solution Route of administration: subcutaneous

Locations

Country	Name	City	State
Germany	Sanofi Administrative Office	Frankfurt

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma concentration (Cmax) of SAR342434, US-approved Humalog and EU-approved Humalog		12 hours	No
Primary	Area under the concentration versus time curve (AUC) of SAR342434, US-approved Humalog and EU-approved Humalog		12 hours	No
Primary	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	No
Secondary	The fractional area under the concentration versus time curve from 0 or y to x hours post administration (INS-AUC0 or Y to X)		12 hours	No
Secondary	Time to 20% of AUC (t20%-AUC)		12 hours	No
Secondary	NS-tmax, INS-t1/2z		12 hours	No
Secondary	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)		12 hours	No
Secondary	Time to 20% of total GIR-AUC0-12h (t20%-GIR-AUC0-12h)		12 hours	No
Secondary	Maximum smoothed body weight standardized GIR (GIRmax)		12 hours	No
Secondary	Time to GIRmax (GIR-tmax)		12 hours	No
Secondary	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)		12 hours	No
Secondary	Number of patients with AEs, SAEs, laboratory, vital signs and electrocardiographic abnormalities , injections site reaction assessment (ISR), and if any, hypoglycemia		8 weeks	Yes