Study of How Single Rising Doses of SAR161271 Are Absorbed and Act in Patients With Type 1 Diabetes Mellitus (T1DM)

Study Overview
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Brief Summary
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Primary Objective: - To establish initial safety/tolerability and pharmacodynamic and pharmacokinetic profiles of four formulations of SAR161271 in patients with T1DM. Secondary Objective: - To establish relative potency of SAR161271 compared with insulin glargine in patients with T1DM

Detailed Description
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The total per patient is between 31 and 67 days; including post-study visit between 108 and 172 days. In case of an additional late post-study visit after last dosing, approximately 213 to 279 days, broken down as follows: Screening: 3 to 27 days; Treatment Periods each 1 day with institutionalisation from Day -1 to Day 3; Wash-out between doses: 7 to 10 days; End of Study visit: 7 to 10 days after last dose. Post-study visit 84 to 112 days after last dosing. If necessary, additional post-study visit 6 to 7 months after last dosing.

Official Title
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Randomized, Double-blind, Euglycemic Glucose Clamp Study of Four Formulations of SAR161271, in Single Doses in Healthy Subjects and Single Ascending Doses in Patients With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: SAR161271
* Drug: Insulin glargine HOE901


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients who have type 1 diabetes mellitus (T1DM) as defined by American Diabetes Association average total insulin dose of <1.2 U/kg/day Fasting negative serum C-peptide (<0.3 nmol/L) Glycated hemoglobin (HbA1c) < or = 9% Stable insulin regimen for at least 2 months before the study Body weight between 50-110 kg inclusive; body mass index between 18-30 kg/m2, inclusive Certified as healthy for T1DM by a comprehensive clinical assessment Exclusion criteria: Any history or presence of clinically relevant (for T1DM) cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness, or major diabetic complications such as diabetic retinopathy. Blood donation, any volume, within 1 month before inclusion. Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician Regular use of any medication other than insulins in the last month before study start with the exception of thyroid hormones, metformin, lipid-lowering and antihypertensive drugs Positive reaction to any of the following tests: hepatitis B surface (HBs) antigen, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus (HIV) 1 antibodies, anti-HIV2 antibodies. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 : SAR161271 0.3 U/kg<br>Cross-over design of four formulation of SAR161271 0.3U/kg or insulin glargine administered as a single dose in the morning between about 11h00 and about 12h00; fasting for about 12h before and for the duration of the clamp | Drug: SAR161271<br>* Pharmaceutical form:Solution for injection Route of administration: subcutaneous<br>Drug: Insulin glargine HOE901<br>* Pharmaceutical form:Solution for injection Route of administration: subcutaneous<br>|
| Experimental: Cohort 2 : SAR161271 0.6 U/kg<br>Cross-over design of four formulation of SAR161271 0.6U/kg or insulin glargine administered as a single dose in the morning between about 11h00 and about 12h00; fasting for about 12h before and for the duration of the clamp | Drug: SAR161271<br>* Pharmaceutical form:Solution for injection Route of administration: subcutaneous<br>Drug: Insulin glargine HOE901<br>* Pharmaceutical form:Solution for injection Route of administration: subcutaneous<br>|
| Experimental: Cohort 3 : SAR161271 1.2 U/kg<br>Cross-over design of four formulation of SAR161271 1.2 U/kg or insulin glargine administered as a single dose in the morning between about 11h00 and about 12h00; fasting for about 12h before and for the duration of the clamp | Drug: SAR161271<br>* Pharmaceutical form:Solution for injection Route of administration: subcutaneous<br>Drug: Insulin glargine HOE901<br>* Pharmaceutical form:Solution for injection Route of administration: subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Safety in terms of adverse and serious adverse events, vital signs, ECG, safety laboratory for each cohort |  | up to 7 days after dose | 
| - Pharmacodynamics (Glucose infusion rate) time-action profile |  | up to 30 hours after dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Pharmacokinetic parameters |  | up to 168 hours after dose | 
| - anti-insulin antibody production |  | pre-dose and after 4th dose |