Relative Bioavailability and Activity of Different Formulations of Insulin Glargine and Lixisenatide in Patients With Diabetes Mellitus Type 1

A Randomized, Cross-over, Open, Euglycemic Clamp Study on the Relative Bioavailability and Activity of 0.6 U/kg Insulin Glargine and 20 μg Lixisenatide, Given as On-site Mix Compared to Separate Simultaneous Injections in Subjects With Type 1 Diabetes Mellitus

Primary Objective:

• to assess the relative bioavailability of a single dose of insulin glargine (Lantus) and lixisenatide given subcutaneously as on-site mix versus separate and simultaneous injections of each drug

Secondary Objectives:

• to compare the activity of a single dose of insulin glargine and lixisenatide given subcutaneously as on-site mix versus separate and simultaneous injections of each drug
• to assess the safety and tolerability of insulin glargine and lixisenatide given subcutaneously as on-site mix

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Insulin glargine HOE901; Drug: Lixisenatide AVE0010

Detailed Description

The study period for one patient is one month in average and it can last up to 7 months (+ 2 weeks) with post-study and follow-up visits

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: 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 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Subjects with type 1 diabetes mellitus for more than one year with total insulin dose of <1.2 U.kg/day, but otherwise healthy with glycohemoglobin (HbA1c) ≤ 9.0%, stable insulin regimen for at least 2 months prior to study, normal finding in medical history and physical examination.

Exclusion criteria:

• any history or presence of clinically relevant cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic (apart from diabetes mellitus type I), hematological, neurological, psychiatric, systemic (affecting the body as a whole), ocular, gynecologic (if female), or infectious disease; any acute 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 severe headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month)
• Symptomatic hypotension, or asymptomatic postural hypotension defined by a decrease in systolic blood pressure (SBP) equal to or greater than 20 mmHg within three minutes when changing from the supine to the standing position
• Presence or history of a drug allergy to clinically significant allergic disease
• Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol
• Pregnant or breast feeding women
• Any medication within 14 days before inclusion, or within 5 times the elimination half-life of that drug, whichever the longest and regular use of any medication other than insulins in the last month before study start with the exception of 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 reaction to any of the following tests: hepatitis B surface (HBs Ag) antigen, antihepatitis B core antibodies (anti-HBc Ab) if compound having possible immune activities, anti-hepatitis C virus (anti-HCV2) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab)
• History of unexplained pancreatitis, chronic pancreatitis and/or pancreatectomy

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
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Lantus(insulin glargine)/lixisenatide on-site mix; Single dose injection of an on site mix of Lantus U100 and lixisenatide (800µg/mL in Lantus U100) at one peri-umbilical site under fasting conditions	Drug: Insulin glargine HOE901; Pharmaceutical form:solution for injection Route of administration: subcutaneous; Drug: Lixisenatide AVE0010; Pharmaceutical form:solution for injection Route of administration: subcutaneous
ACTIVE_COMPARATOR: lixisenatide + Lantus (insulin glargine); Single dose, separate injection simultaneous injections of Lantus U100 and lixisenatide (100µg/mL) at opposite peri-umbilical sites within 1 minute under fasting conditions	Drug: Insulin glargine HOE901; Pharmaceutical form:solution for injection Route of administration: subcutaneous; Drug: Lixisenatide AVE0010; Pharmaceutical form:solution for injection Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma lixisenatide concentration curve (LIX-AUClast)	1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
Lixisenatide maximum plasma/serum peak concentration (LIX-Cmax)	1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma lixisenatide concentration curve (AUC)	1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
Time to Cmax (Tmax ) for lixisenatide	1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
Area under the body weight standardized glucose infusion rate curve (GIR) within 24 h (GIR-AUC0-24)	1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
Time to 50% of the GIR-AUC within 24 h (T50%-GIR AUC0-24)	1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
Maximum smoothed body weight standardized glucose infusion rate GIRmax	1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
Time to GIRmax (GIR-Tmax)	1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): September 1, 2010
• Study Completion (ACTUAL): January 1, 2011

Study Registration Dates

• First Submitted: June 16, 2010
• First Submitted That Met QC Criteria: June 16, 2010
• First Posted (ESTIMATE): June 17, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): March 2, 2011
• Last Update Submitted That Met QC Criteria: March 1, 2011
• Last Verified: March 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; Lixisenatide
• Other Study ID Numbers: BDR11578; 2010-019228-30 (EUDRACT_NUMBER); U1111-1116-8960 (OTHER: UTN)