Single Dose Clamp Study To Compare Concentration/Time Profile And Metabolic Activity Profile Of 2 New Formulations Of Insulin Glargine With Lantus

Type 1 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02201199
• Other study ID #: PDY13928
• Secondary ID: 2014-001252-33U1
• Status: Completed
• Phase: Phase 1
• First received: July 24, 2014
• Last updated: December 23, 2014
• Start date: August 2014
• Est. completion date: November 2014

Study information

• Verified date: December 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• insulin glargine U200 HOE901
Pharmaceutical form:solution for injection Route of administration: subcutaneous
• insulin glargine U500 HOE901
Pharmaceutical form:solution for injection Route of administration: subcutaneous
• insulin glargine U100 HOE901
Pharmaceutical form:solution for injection Route of administration: subcutaneous

Locations

Country	Name	City	State
Germany	Investigational Site Number 276001	Neuss

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the serum insulin glargine (INS) concentration curve over the first 12 hours after dosing		12 hours	No
Secondary	INS-Area Under the Curve (AUC) over 24 and 36 hours after dosing (INS AUC 0-24 and INS AUC 0-36)		36 hours	No
Secondary	AUC up to the last measurable concentration		36 hours	No
Secondary	Time to reach 50% of INS-AUC 0-36		36 hours	No
Secondary	Time to reach INS-Cmax (INS-tmax)		36 hours	No
Secondary	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)		36 hours	No
Secondary	Time to reach 50% of GIR-AUC0-36 (T50%-GIR-AUC0-36)		36 hours	No
Secondary	Maximum smoothed body weight standardized glucose infusion rate (GIRmax) and time to GIRmax (GIR-Tmax)		36 hours	No
Secondary	Duration of blood glucose control (time to elevation of smoothed blood glucose profile above different pre-specific blood glucose levels)		4 days	Yes
Secondary	Safety and tolerability (Number of patients with adverse events, clinically significant changes in vital signs, laboratory parameters)		4 days	Yes