Euglycemic Clamp Dose-response Study Comparing a New Insulin Glargine Formulation With Lantus®

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01195454
First received: September 3, 2010
Last updated: October 28, 2011
Last verified: October 2011
  Purpose

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

Condition Intervention Phase
Type 1 Diabetes Mellitus
Drug: Insulin glargine (HOE901)
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • The area under the body weight standardized glucose infusion rate curve (GIR) within 36 hours (GIR-AUC0-36) [ Time Frame: 36 hours (D1 to D2) in all four treatment periods ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The area under the insulin glargine concentration curve within 36 hours (INS-AUC0-36) - [ Time Frame: 36 hours (D1 to D2) in all four treatment periods ] [ Designated as safety issue: No ]
  • Time to 50% of the GIR-AUC0-36 (T50%-GIR AUC0-36) [ Time Frame: 36 hours (D1 to D2) in all four treatment periods ] [ Designated as safety issue: No ]
  • Time to 50% of INS-AUC0-36 (T50% INS-AUC0-36) [ Time Frame: 36 hours (D1 to D2) in all four treatment periods ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: 36 hours (D1 to D2) in all four treatment periods ] [ Designated as safety issue: No ]
  • Maximum smoothed body weight standardized glucose infusion rate GIRmax, and time to GIRmax (GIR-Tmax) [ Time Frame: 36 hours (D1 to D2) in all four treatment periods ] [ Designated as safety issue: No ]
  • Maximum insulin concentration INS-Cmax, and time to Cmax (INS-Tmax) [ Time Frame: 36 hours (D1 to D2) in all four treatment periods ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: August 2010
Study Completion Date: December 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Insulin glargine / New insulin glargine formulation
  • Period 1: Insulin glargine
  • Period 2: New insulin glargine formulation
  • Period 3: New insulin glargine formulation
  • Period 4: New insulin glargine formulation

Duration of treatment: 1 day at each period

Drug: Insulin glargine (HOE901)

Pharmaceutical form: Lantus solution for injection

Route of administration: subcutaneous

Drug: Insulin glargine (HOE901)

Pharmaceutical form: New insulin glargine formulation solution for injection

Route of administration: subcutaneous


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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01195454

Locations
Germany
Sanofi-Aventis Administrative Office
Berlin, Germany
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01195454     History of Changes
Other Study ID Numbers: PKD11627, 2010-020914-27
Study First Received: September 3, 2010
Last Updated: October 28, 2011
Health Authority: Germany: Ethics Commission

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Glargine
Insulin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014