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

Type1 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01838083
• Other study ID #: PKD13560
• Secondary ID: 2012-005777-31U1
• Status: Completed
• Phase: Phase 1
• First received: April 16, 2013
• Last updated: August 9, 2013
• Start date: April 2013
• Est. completion date: August 2013

Study information

• Verified date: August 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type1 Diabetes

Intervention

Drug:
• Insulin glargine new formulation HOE901
Pharmaceutical form: solution 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 concentration curve within 24 hours (INS-AUC0-24) after dosing on Day 6		24-hours (D6 to D7)	No
Secondary	Maximum insulin concentration (INS-Cmax)		24-hours (D6 to D7)	No
Secondary	Time to INS-Cmax (INS-tmax)		24-hours (D6 to D7)	No
Secondary	Time to reach 50% of INS-AUC0-24 (T50%-INS-AUC0-24)		24-hours (D6 to D7)	No
Secondary	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)	No
Secondary	Maximum smoothed body weight standardized glucose infusion rate (GIRmax)		24-hours (D6 to D7)	No
Secondary	Time to GIRmax (GIR-Tmax)		24-hours (D6 to D7)	No
Secondary	Time to reach at least 50% of GIR-AUC0-24 (T50%-GIR-AUC0-24)		24-hours (D6 to D7)	No
Secondary	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)	No
Secondary	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	Yes