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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Glargine
Insulin
Insulin, Globin Zinc
Insulin, Long-Acting
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014