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

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

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

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: SAR161271; Drug: Insulin glargine HOE901

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 : SAR161271 0.3 U/kg; 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; Pharmaceutical form:Solution for injection Route of administration: subcutaneous; Drug: Insulin glargine HOE901; Pharmaceutical form:Solution for injection Route of administration: subcutaneous
Experimental: Cohort 2 : SAR161271 0.6 U/kg; 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; Pharmaceutical form:Solution for injection Route of administration: subcutaneous; Drug: Insulin glargine HOE901; Pharmaceutical form:Solution for injection Route of administration: subcutaneous
Experimental: Cohort 3 : SAR161271 1.2 U/kg; 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; Pharmaceutical form:Solution for injection Route of administration: subcutaneous; Drug: Insulin glargine HOE901; Pharmaceutical form:Solution for injection Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: January 19, 2010
• First Submitted That Met QC Criteria: January 19, 2010
• First Posted (Estimate): January 21, 2010

Study Record Updates

• Last Update Posted (Estimate): July 26, 2011
• Last Update Submitted That Met QC Criteria: July 25, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Glargine
• Other Study ID Numbers: TDU10987; TDU10948