Clinical trial NCT01146678: Relative Bioavailability and Activity of Different Formulations of Insulin Glargine and Lixisenatide in Patients With Diabetes Mellitus Type 1
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-06-17
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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

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

Eligibility criteria: 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.

Primary outcomes:
measure: Area under the plasma lixisenatide concentration curve (LIX-AUClast)
timeFrame: 1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
measure: Lixisenatide maximum plasma/serum peak concentration (LIX-Cmax)
timeFrame: 1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
Secondary outcomes:
measure: Area under the plasma lixisenatide concentration curve (AUC)
timeFrame: 1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
measure: Time to Cmax (Tmax ) for lixisenatide
timeFrame: 1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
measure: Area under the body weight standardized glucose infusion rate curve (GIR) within 24 h (GIR-AUC0-24)
timeFrame: 1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
measure: Time to 50% of the GIR-AUC within 24 h (T50%-GIR AUC0-24)
timeFrame: 1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
measure: Maximum smoothed body weight standardized glucose infusion rate GIRmax
timeFrame: 1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
measure: Time to GIRmax (GIR-Tmax)
timeFrame: 1 day (D1 to D2) in the first treatment period and 1 day (D1 to D2) during the second treatment period
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: