Clinical trial NCT01195454: Euglycemic Clamp Dose-response Study Comparing a New Insulin Glargine Formulation With Lantus®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-09-06
Enrollment: 24
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 total metabolic effect ratios of a new insulin glargine formulation versus Lantus®

Secondary Objectives:

* To assess the exposure ratios of a new insulin glargine formulation versus Lantus®
* To compare the duration of action of a new insulin glargine formulation versus Lantus®
* To explore the dose response and dose exposure relationship of a new insulin glargine formulation
* To assess the safety and tolerability of a new insulin glargine formulation

Detailed description: The study period for one patient is one month in average and it can last up to 11 weeks broken down as follows:

* Screening: 3 to 28 days
* Treatment period: 1 to 4 days: 2 days (1 overnight stay)
* Washout period: 5 to 18 days (preferentially 7 days between consecutive dosings)
* End of study: 1 day after the last dosing

Eligibility criteria: 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,
* Glycohemoglobin (HbA1c) ≤ 9.0%,
* Fasting negative serum C-peptide (\< 0.3 nmol/L),
* 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,
* Women of childbearing potential with negative pregnancy test and use of a highly effective contraceptive method or women with confirmed postmenopausal status.

Exclusion criteria:

* Any history or presence of clinically relevant cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic (apart from diabetes mellitus type 1), 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 (whatever the decrease in blood pressure), or asymptomatic postural hypotension defined by a decrease in 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 or 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 (including St John's Wort) within 14 days before inclusion, or within 5 times the elimination half-life or pharmacodynamic 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),
* Known hypersensitivity to insulin glargine and excipients,
* Any history or presence of deep leg vein thrombosis.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: The area under the body weight standardized glucose infusion rate curve (GIR) within 36 hours (GIR-AUC0-36)
timeFrame: 36 hours (D1 to D2) in all four treatment periods
Secondary outcomes:
measure: The area under the insulin glargine concentration curve within 36 hours (INS-AUC0-36) -
timeFrame: 36 hours (D1 to D2) in all four treatment periods
measure: Time to 50% of the GIR-AUC0-36 (T50%-GIR AUC0-36)
timeFrame: 36 hours (D1 to D2) in all four treatment periods
measure: Time to 50% of INS-AUC0-36 (T50% INS-AUC0-36)
timeFrame: 36 hours (D1 to D2) in all four treatment periods
measure: 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)
timeFrame: 36 hours (D1 to D2) in all four treatment periods
measure: Maximum smoothed body weight standardized glucose infusion rate GIRmax, and time to GIRmax (GIR-Tmax)
timeFrame: 36 hours (D1 to D2) in all four treatment periods
measure: Maximum insulin concentration INS-Cmax, and time to Cmax (INS-Tmax)
timeFrame: 36 hours (D1 to D2) in all four treatment periods
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: