Euglycemic Clamp Study Comparing Two New Insulin Glargine Formulations in Subjects With Type 1 Diabetes Mellitus

A Double-blind, Randomized, Two-treatment Crossover Bioequivalence Study Comparing Two New Insulin Glargine Formulations Using the Euglycemic Clamp Technique in Subjects With Type 1 Diabetes Mellitus

Primary Objective:

To demonstrate equivalence in exposure to insulin glargine given as test formulation T and reference formulation R in steady state conditions after 6 once-daily subcutaneous (SC) doses

Secondary Objective:

• To assess relative Pharmacodynamic activity of the insulin glargine test formulation T to the insulin glargine reference formulation R in steady state conditions after 6 once-daily SC doses
• To assess the safety and tolerability of the test and reference formulations of two new insulin glargine formulations

Study Overview

• Status: Completed
• Conditions: Type1 Diabetes
• Intervention / Treatment: Drug: Insulin glargine new formulation HOE901

Detailed Description

Total study duration per subject: 29 to 64 days including screening visit

Duration of each part of the study for one subject:

• Screening: 3 to 21 days before 1st dosing (Day -21 to Day -3)
• Treatment Period 1 and 2: 8 days (dosing on 6 days)
• Washout between last/1st dosing days of the treatment periods: 7-21 days (preferentially 7 days) End-of-Study Visit: 7-10 days after last dosing

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Investigational Site Number 276001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Male or female subjects, between 18 and 64 years of age, inclusive, with diabetes mellitus type 1 for more than one year
• Total insulin dose of < 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
• Laboratory parameters within the normal range
• 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 systolic blood pressure 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 according to the Investigator's judgment
• Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol
• Presence or history of drug or alcohol abuse (alcohol consumption > 40 grams / day)
• If female, pregnancy (defined as positive Beta Human Chorionic Gonadotropin test), breast-feeding
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin glargine new formulation (test T formulation); Once daily for 6 days	Drug: Insulin glargine new formulation HOE901; Pharmaceutical form: solution Route of administration: subcutaneous
Experimental: Insulin glargine new formulation (reference R formulation); Once daily for 6 days	Drug: Insulin glargine new formulation HOE901; Pharmaceutical form: solution Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the serum insulin concentration curve within 24 hours (INS-AUC0-24) after dosing on Day 6	24-hours (D6 to D7)

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum insulin concentration (INS-Cmax)	24-hours (D6 to D7)
Time to INS-Cmax (INS-tmax)	24-hours (D6 to D7)
Time to reach 50% of INS-AUC0-24 (T50%-INS-AUC0-24)	24-hours (D6 to D7)
Area under the body-weight-standardized Glucose Infusion Rate (GIR) within 24 hours (GIR-AUC0-24h) after dosing on Day 6 during the clamp	24-hours (D6 to D7)
Maximum smoothed body weight standardized glucose infusion rate (GIRmax)	24-hours (D6 to D7)
Time to GIRmax (GIR-Tmax)	24-hours (D6 to D7)
Time to reach at least 50% of GIR-AUC0-24 (T50%-GIR-AUC0-24)	24-hours (D6 to D7)
Duration of blood glucose control (time to elevation of smoothed blood glucose profile above clamp level and to elevation above different prespecified blood glucose levels)	24-hours (D6 to D7)
Safety as measured by adverse events/serious adverse events, ohypoglycemia events, physical examinations, clinical laboratory, electrocardiograms, vital signs, injection site reactions and anti-insulin antibodies.	up to 9 weeks

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: April 16, 2013
• First Submitted That Met QC Criteria: April 18, 2013
• First Posted (Estimate): April 23, 2013

Study Record Updates

• Last Update Posted (Estimate): August 13, 2013
• Last Update Submitted That Met QC Criteria: August 9, 2013
• Last Verified: August 1, 2013

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
• Other Study ID Numbers: PKD13560; 2012-005777-31 (EudraCT Number); U1111-1139-3755 (Other Identifier: UTN)