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

Condition(s) targeted: Type 1 Diabetes Mellitus

Intervention: Insulin glargine (HOE901) (Drug); Neutral Protamine Hagedorn (NPH) insulin (Drug); Insulin lispro (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Sanofi

Official(s) and/or principal investigator(s):
Clinical Sciences & Operations, Study Director, Affiliation: Sanofi

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

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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)

Secondary outcome:

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)

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

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

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

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

Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment

Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment (ANCOVA Estimates)

Percentage of Patients Reaching HbA1c Target of Less Than 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

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

Minimum age: 1 Year. Maximum age: 6 Years. Gender(s): Both.

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.

Sanofi-Aventis Investigational Site Number 040001, Wien 1090, Austria

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Starting date: October 2009
Last updated: June 25, 2012