Clinical trial NCT02201199: Single Dose Clamp Study To Compare Concentration/Time Profile And Metabolic Activity Profile Of 2 New Formulations Of Insulin Glargine With Lantus
Official title: A Single-Center, Randomized, Double-Blind, 3-Treatment, 3-Period, 6-Sequence Cross-Over Study To Compare The Pharmacokinetic And Pharmacodynamic Effects of Single Doses of Insulin Glargine Given As U200 And U500 To Lantus® In A Euglycemic Clamp Setting In Subjects With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2014-07-25
Enrollment: 36
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: BASIC_SCIENCE

Brief summary: Primary Objective:

To compare the pharmacokinetic (PK) characteristics of single doses of insulin glargine given as U200 and U500 with those of a single dose (SD) of Lantus® U100 in a euglycemic clamp setting in subjects with type 1 diabetes.

Secondary Objectives:

To compare the metabolic activity characteristics of single doses of insulin glargine given as U200 and U500 with those of a single dose of Lantus® U100 in a euglycemic clamp setting in subjects with type 1 diabetes.

To assess the safety and tolerability of single doses of U200, U500 and Lantus® U100 in subjects with type 1 diabetes.

Detailed description: Total study duration for each subject is between 3.5 and 12 weeks.

Two overnight stays at the unit in each of 3 treatment periods.

Eligibility criteria: Inclusion criteria:

* Male or female subjects, between 18 and 65 years of age, inclusive, with type 1 diabetes mellitus for more than one year, as defined by the American Diabetes Association.
* Total insulin dose \<1.2 U/kg/day.
* Minimum usual basal insulin dose ≥0.2 U/kg/day.
* Body weight between 50.0 kg and 110.0 kg, Body Mass Index between 18.5 and 30.0 kg/m2 inclusive.
* Fasting negative serum C-peptide (\<0.3 nmol/L).
* Glycohemoglobin (HbA1c) ≤75 mmol/mol (≤9.0%).
* Stable insulin regimen for at least 2 months prior to inclusion in study.
* Certified as otherwise healthy for Type 1 diabetes mellitus patient.
* Women of childbearing potential with negative pregnancy test and use of a highly effective contraceptive method or women with confirmed postmenopausal status.
* Having given written informed consent prior to undertaking any study-related procedure.

Exclusion criteria:

* 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).
* Presence or history of a drug allergy or clinically significant allergic disease according to the Investigator's judgment.
* Presence or history of drug or alcohol abuse (alcohol consumption \>40 grams / day).
* Smoking more than 5 cigarettes or equivalent per day, unable to refrain from smoking.
* 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 in the last month before study start with the exception of insulin products, 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; any biologics (antibody or its derivatives) given within 4 months before randomization.
* Known hypersensitivity to insulin glargine or excipients of the study drug.
* Any history or presence of deep leg vein thrombosis or a frequent appearance of deep leg vein thrombosis in first degree relatives (parents, siblings or children).

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 serum insulin glargine (INS) concentration curve over the first 12 hours after dosing
timeFrame: 12 hours
Secondary outcomes:
measure: INS-Area Under the Curve (AUC) over 24 and 36 hours after dosing (INS AUC 0-24 and INS AUC 0-36)
timeFrame: 36 hours
measure: AUC up to the last measurable concentration
timeFrame: 36 hours
measure: Time to reach 50% of INS-AUC 0-36
timeFrame: 36 hours
measure: Time to reach INS-Cmax (INS-tmax)
timeFrame: 36 hours
measure: Area under the body-weight-standardized Glucose Infusion Rate (GIR) over the first 12, 24 and 36 hours after dosing (GIR-AUC0-12, GIR-AUC0-24 and, GIR-AUC0-36)
timeFrame: 36 hours
measure: Time to reach 50% of GIR-AUC0-36 (T50%-GIR-AUC0-36)
timeFrame: 36 hours
measure: Maximum smoothed body weight standardized glucose infusion rate (GIRmax) and time to GIRmax (GIR-Tmax)
timeFrame: 36 hours
measure: Duration of blood glucose control (time to elevation of smoothed blood glucose profile above different pre-specific blood glucose levels)
timeFrame: 4 days
measure: Safety and tolerability (Number of patients with adverse events, clinically significant changes in vital signs, laboratory parameters)
timeFrame: 4 days
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Investigational Site Number 276001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: