6-month Comparison of Morning Lantus Versus Neutral Protamine Hagedorn Insulin in Young Children With Type 1 Diabetes
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Insulin glargine (HOE901); Neutral Protamine Hagedorn (NPH) insulin; Insulin lispro
Intervention description: 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%.; 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; 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.
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Lispro; Protamines
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 125.0
Sex: All
Minimum age: 1 Year
Maximum age: 6 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility 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.