6-month Comparison of Morning Lantus Versus Neutral Protamine Hagedorn Insulin in Young Children With Type 1 Diabetes (PRESCHOOL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00993473
First received: October 9, 2009
Last updated: June 25, 2012
Last verified: June 2012
  Purpose

The primary study objective was to compare the rate of "all hypoglycemia" (composite outcome of the following hypoglycemia events: symptomatic hypoglycemia episodes, low continuous glucose monitoring system (CGMS) excursions confirmed by fingerstick blood glucose (FSBG), low FSBG readings performed at other times) between children treated with Lantus (insulin glargine) and Neutral Protamine Hagedorn (NPH) insulin.

Secondary objectives were to compare insulin glargine and NPH in terms of:

  • rates of specific types of hypoglycemia: symptomatic, severe, nocturnal, nocturnal symptomatic, and severe nocturnal symptomatic hypoglycemia
  • HbA1c change from baseline to end-of-treatment, and HbA1c at end-of-treatment
  • percentage of patients reaching HbA1c less than 7.5% (target value) at end of treatment
  • average blood glucose over whole trial and at end of trial, as estimated by continuous glucose monitoring (CGM), and blood glucose variability

Condition Intervention Phase
Type 1 Diabetes Mellitus
Drug: Insulin glargine (HOE901)
Drug: Neutral Protamine Hagedorn (NPH) insulin
Drug: Insulin lispro
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 24-week, Randomized, Open-label, Parallel Group Multinational Comparison of Lantus® (Insulin Glargine) Given in the Morning as Once-a-day Basal Insulin Versus Neutral Protamine Hagedorn (NPH) Insulin, in Children With Type 1 Diabetes Mellitus Aged at Least 1 Year to Less Than 6 Years

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Event Rate of "All Hypoglycemia" Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years (Events Per Patient-year) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    The rate of "all hypoglycemia" was calculated from "all hypoglycemia" episodes which occurred during the 24-week on-treatment period and consisted of: - symptomatic hypoglycemia episodes validated by the study investigator based on entries in patients' diaries, - low continuous glucose monitoring system (CGMS) excursions (interstitial glucose <70 mg/dL [3.9 mmol/L]) confirmed by fingerstick blood glucose (FSBG) <70 mg/dL, - low FSBG readings (values <70 mg/dL) performed at other times.


Secondary Outcome Measures:
  • Event Rate of Symptomatic Hypoglycemia (Individual Component of Primary Endpoint) Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years (Events Per Patient-year) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Symptomatic hypoglycemia: any event with clinical symptoms considered to result from hypoglycemia, validated by the study investigator based on data from patient diaries.

  • Event Rate of Severe Symptomatic Hypoglycemia Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Severe symptomatic hypoglycemia: any event with clinical symptoms considered to result from a hypoglycemic episode for which the patients required the assistance of a third party (ie, other than the patient, or a parent/usual caregiver; eg, from emergency personnel), because the patients/parents could not treat the event with acute neurological impairment directly resulting from the hypoglycemic event. The occurrence of seizure, coma, unconsciousness, or the use of glucagon, were also to qualify a hypoglycemic episode as severe.

  • Event Rate of Nocturnal Hypoglycemia Defined as the Total Number of "All Hypoglycemia" Episodes Divided by the Total Duration of the On-treatment Period in Years [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Nocturnal hypoglycemia: any event from the "all hypoglycemia" total that occurred between 23:00 and 07:00 hours.

  • Event Rate of Nocturnal Symptomatic Hypoglycemia Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Nocturnal symptomatic hypoglycemia: any symptomatic hypoglycemic event that occurred between 23:00 and 07:00 hours.

  • Event Rate of Severe Nocturnal Hypoglycemia Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Severe nocturnal symptomatic hypoglycemia: any severe symptomatic hypoglycemic event that occurred between 23:00 and 07:00 hours.

  • Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
  • Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment (ANCOVA Estimates) [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    Assessed using an analysis of covariance (ANCOVA) model with treatment, and randomization strata (baseline number of CGM hypoglycemic excursions <0.5 events/24hours or ≥0.5 events/24 hours, and baseline HbA1c <8.5% or ≥8.5%) as fixed effects, and using the baseline value as covariate.

  • Percentage of Patients Reaching HbA1c Target of Less Than 7.5% at the End of Treatment Visit [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Percentage of patients reaching International Society for Pediatric and Adolescent Diabetes (ISPAD)-recommended goals of Glycosylated Hemoglobin A1c <7.5% at the end of treatment visit.

  • Average Daily Blood Glucose (BG) Based on CGMS Values: End of Treatment and Change From Baseline to End of Treatment [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]

Enrollment: 125
Study Start Date: October 2009
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lantus (insulin glargine)
Lantus given as basal insulin once a day in the morning by subcutaneous injection
Drug: Insulin glargine (HOE901)

100 U/mL commercial solution for injection available as both disposable pen devices Solostar® each containing 300 U and as 10 mL vials each containing 1000 U

Dose: titrated to achieve the following glycemic targets without hypoglycemia:

  • Fasting blood glucose (BG) between 90 and 145 mg/dL (5.0 to 8.0 mmol/L), inclusive,
  • Bedtime BG between 120 and 180 mg/dL (6.7 to10.0 mmol/L), inclusive,
  • Nocturnal BG between 80 and 162 mg/dL (4.4 to 9.0 mmol/L), inclusive; and
  • HbA1c <7.5%.
Other Name: Lantus®
Drug: Insulin lispro
Insulin lispro used as the principal bolus insulin; regular human insulin permitted. Administration: multiple injection before meals and/or at bedtime at the discretion of the Investigator.
Other Name: Humalog®
Active Comparator: NPH insulin
Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day generally in the morning and /or at bedtime by subcutaneous injection
Drug: Neutral Protamine Hagedorn (NPH) insulin

NPH insulin 100 U/mL commercial (Huminsulin Basal) solution for injection available as both disposable pen devices (Huminsulin Basal Pen) each containing 300 U and as 10 mL vials each containing 1000 U

Dose: titrated to achieve glycemic targets as described above for insulin glargine

Drug: Insulin lispro
Insulin lispro used as the principal bolus insulin; regular human insulin permitted. Administration: multiple injection before meals and/or at bedtime at the discretion of the Investigator.
Other Name: Humalog®

Detailed Description:

Screening phase: 2 to 4 weeks

Treatment phase: 24 weeks

At randomization, patients were stratified with respect to their baseline HbA1c level (<8.5% or ≥8.5%) and hypoglycemic event rate (number of CGMS hypoglycemic excursions <0.5 or ≥0.5 events per 24 hours). Following randomization, trial basal insulin was initiated and up-titrated within the first 12 weeks to reach a stable dose.

Follow-up phase: 2 weeks

All Phases: 28 to 30 weeks

  Eligibility

Ages Eligible for Study:   1 Year to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Pediatric patients with type 1 diabetes mellitus aged at least one year to less than 6 years at screening, for whom signed written informed consent has been obtained from parent or legal guardian to participate in the study

Exclusion criteria:

  • Diagnosis of type 1 diabetes for less than one year
  • HbA1c at screening >12% or <6%
  • Diabetes other than type 1 diabetes
  • Parents and patients not willing to undergo all study assessments and treatments, including home blood glucose monitoring, Continuous Glucose Monitoring System (CGMS) sensor placement and maintenance both at the site and at home, multiple daily insulin injections, and visits, as dictated by the protocol (if a telephone is not available patients may undergo all visits in person)
  • Patients and families for whom 6 days in total (not necessarily continuous) of useable CGMS data cannot be obtained (either by home sensor replacement, or by sensor replacement at the site at additional screening visits if needed) during the screening CGMS evaluations between Visit 2 and the randomization visit
  • Patients treated with insulin pump therapy during the two months prior to screening
  • History of primary seizure disorder
  • History of severe hypoglycemic episode accompanied by seizure and/or coma, or diabetic ketoacidosis leading to hospitalization or to care in the emergency ward, in the 2 months prior to the screening visit
  • Need for chronic treatment with acetaminophen (paracetamol)-containing medications
  • Serum creatinine > 2.0mg/dL at screening
  • Serum ALT or AST greater than 3x upper limit of normal for the patient's age and gender, at screening
  • Hemoglobin < 10g/dL, or platelet count less than 100,000/cu mm, at screening
  • Treatment with any pharmacologic anti-hyperglycemic oral agent for more than 3 months at any time
  • Treatment with any non-insulin antihyperglycemic medication (eg, Symlin®) for the 3 months prior to screening
  • Treatment with systemic glucocorticoids within the month prior to screening

Above information 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: NCT00993473

  Hide Study Locations
Locations
United States, California
Sanofi-Aventis Investigational Site Number 840006
Sacramento, California, United States, 95819
Sanofi-Aventis Investigational Site Number 840014
San Diego, California, United States, 92123
United States, Colorado
Sanofi-Aventis Investigational Site Number 840005
Greenwood Village, Colorado, United States, 80111
United States, Maryland
Sanofi-Aventis Investigational Site Number 840008
Baltimore, Maryland, United States, 21229
United States, New York
Sanofi-Aventis Investigational Site Number 840007
Buffalo, New York, United States, 14222
United States, Pennsylvania
Sanofi-Aventis Investigational Site Number 840011
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Sanofi-Aventis Investigational Site Number 840010
Houston, Texas, United States, 77030
Sanofi-Aventis Investigational Site Number 840002
San Antonio, Texas, United States, 78229
Austria
Sanofi-Aventis Investigational Site Number 040001
Wien, Austria, 1090
Brazil
Sanofi-Aventis Investigational Site Number 076001
Brasilia, Brazil, 71625-009
Sanofi-Aventis Investigational Site Number 076003
Curitiba, Brazil, 80810-040
Sanofi-Aventis Investigational Site Number 076004
Fortaleza, Brazil, 60430-370
Sanofi-Aventis Investigational Site Number 076005
Fortaleza, Brazil, 60135-170
Sanofi-Aventis Investigational Site Number 076002
Porto Alegre, Brazil, 91350-250
Sanofi-Aventis Investigational Site Number 076006
Rio De Janeiro, Brazil, 20211-340
Chile
Sanofi-Aventis Investigational Site Number 152003
Santiago, Chile, 8207257
Sanofi-Aventis Investigational Site Number 152001
Santiago, Chile, 8910095
Sanofi-Aventis Investigational Site Number 152002
Santiago, Chile, 7830489
Sanofi-Aventis Investigational Site Number 152004
Viña Del Mar, Chile, 257-0017
Czech Republic
Sanofi-Aventis Investigational Site Number 203001
Olomouc, Czech Republic, 77520
Sanofi-Aventis Investigational Site Number 203003
Pardubice, Czech Republic, 53203
Sanofi-Aventis Investigational Site Number 203002
Usti Nad Labem, Czech Republic, 40113
Germany
Sanofi-Aventis Investigational Site Number 276002
Düsseldorf, Germany, 40225
Sanofi-Aventis Investigational Site Number 276003
Münster, Germany, 48155
Hungary
Sanofi-Aventis Investigational Site Number 348004
Budapest, Hungary, 1023
Sanofi-Aventis Investigational Site Number 348005
Budapest, Hungary, 1089
Sanofi-Aventis Investigational Site Number 348003
Miskolc, Hungary, 3526
Sanofi-Aventis Investigational Site Number 348002
Szeged, Hungary, 6701
Sanofi-Aventis Investigational Site Number 348001
Szombathely, Hungary, 9700
India
Sanofi-Aventis Investigational Site Number 356001
Bangalore, India
Sanofi-Aventis Investigational Site Number 356005
Bangalore, India, 560052
Sanofi-Aventis Investigational Site Number 356003
Bangalore, India, 560043
Sanofi-Aventis Investigational Site Number 356002
Indore, India, 452001
Sanofi-Aventis Investigational Site Number 356004
Karnal, India, 132001
Mexico
Sanofi-Aventis Investigational Site Number 484002
Guadalajara, Mexico, 44620
Sanofi-Aventis Investigational Site Number 484003
Monterrey, Mexico, 64640
Sanofi-Aventis Investigational Site Number 484001
Puebla, Mexico, 72190
Peru
Sanofi-Aventis Investigational Site Number 604001
Lima, Peru
Sanofi-Aventis Investigational Site Number 604002
Lima, Peru, Lima 5
Sanofi-Aventis Investigational Site Number 604003
Lima, Peru, Lima 01
Poland
Sanofi-Aventis Investigational Site Number 616002
Gdansk, Poland
Sanofi-Aventis Investigational Site Number 616001
Warszawa, Poland, 04-730
Romania
Sanofi-Aventis Investigational Site Number 642008
Bucharest, Romania, 041451
Sanofi-Aventis Investigational Site Number 642001
Cluj Napoca, Romania, 400370
Sanofi-Aventis Investigational Site Number 642011
Constanta, Romania, 900591
Sanofi-Aventis Investigational Site Number 642006
Sibiu, Romania, 550166
Russian Federation
Sanofi-Aventis Investigational Site Number 643001
Moscow, Russian Federation, 117036
Sanofi-Aventis Investigational Site Number 643002
Moscow, Russian Federation, 119049
Sanofi-Aventis Investigational Site Number 643003
St-Petersburg, Russian Federation, 193144
Sanofi-Aventis Investigational Site Number 643004
Ufa, Russian Federation, 450000
Sanofi-Aventis Investigational Site Number 643005
Yaroslavl, Russian Federation, 150042
South Africa
Sanofi-Aventis Investigational Site Number 710004
Durban, South Africa
Sanofi-Aventis Investigational Site Number 710002
Johannesburg, South Africa, 2193
Sanofi-Aventis Investigational Site Number 710001
Observatory, South Africa, 7925
Sanofi-Aventis Investigational Site Number 710003
Pretoria, South Africa, 0084
Spain
Sanofi-Aventis Investigational Site Number 724003
Santiago De Compostela, Spain, 15706
Sanofi-Aventis Investigational Site Number 724001
Sevilla, Spain, 41013
Sanofi-Aventis Investigational Site Number 724005
Valencia, Spain, 46010
Sanofi-Aventis Investigational Site Number 724004
Zaragoza, Spain, 50009
Turkey
Sanofi-Aventis Investigational Site Number 792001
Ankara, Turkey, 06100
Sanofi-Aventis Investigational Site Number 792003
Istanbul, Turkey, 34000
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00993473     History of Changes
Other Study ID Numbers: EFC11202, 2009-011231-12
Study First Received: October 9, 2009
Results First Received: March 28, 2012
Last Updated: June 25, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Glargine
Isophane insulin, beef
Insulin
Insulin, Long-Acting
Insulin Lispro
Insulin, Isophane
Protamines
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Heparin Antagonists
Molecular Mechanisms of Pharmacological Action
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014