Clinical trial NCT00993473: 6-month Comparison of Morning Lantus Versus Neutral Protamine Hagedorn Insulin in Young Children With Type 1 Diabetes
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-10-12
Enrollment: 125
Sex: ALL
Minimum age (years): 1
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

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 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.

Primary outcomes:
measure: 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)
timeFrame: 6 months
Secondary outcomes:
measure: 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)
timeFrame: 6 months
measure: 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
timeFrame: 6 months
measure: 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
timeFrame: 6 months
measure: 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
timeFrame: 6 months
measure: 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
timeFrame: 6 months
measure: Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment
timeFrame: baseline, 6 months
measure: Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment (ANCOVA Estimates)
timeFrame: baseline, 6 months
measure: Percentage of Patients Reaching HbA1c Target of Less Than 7.5% at the End of Treatment Visit
timeFrame: 6 months
measure: Average Daily Blood Glucose (BG) Based on CGMS Values: End of Treatment and Change From Baseline to End of Treatment
timeFrame: baseline, 6 months
Other outcomes:
measure: Number of Patients With Different Types of Hypoglycemia Events
timeFrame: 6 months
measure: Percent of Blood Glucose (BG) Within the Range of 70 - 180 mg/dL (3.9-10 mmol/L)
timeFrame: 6 months
measure: Blood Glucose Variability Based on All On-treatment CGMS Values
timeFrame: 6 months
measure: Nocturnal Blood Glucose Variability Based on All On-treatment CGMS Values
timeFrame: 6 months
Locations:
city: Sacramento
country: United States
facility: Sanofi-Aventis Investigational Site Number 840006
state: California
city: San Diego
country: United States
facility: Sanofi-Aventis Investigational Site Number 840014
state: California
city: Greenwood Village
country: United States
facility: Sanofi-Aventis Investigational Site Number 840005
state: Colorado
city: Baltimore
country: United States
facility: Sanofi-Aventis Investigational Site Number 840008
state: Maryland
city: Buffalo
country: United States
facility: Sanofi-Aventis Investigational Site Number 840007
state: New York
city: Philadelphia
country: United States
facility: Sanofi-Aventis Investigational Site Number 840011
state: Pennsylvania
city: Houston
country: United States
facility: Sanofi-Aventis Investigational Site Number 840010
state: Texas
city: San Antonio
country: United States
facility: Sanofi-Aventis Investigational Site Number 840002
state: Texas
city: Wien
country: Austria
facility: Sanofi-Aventis Investigational Site Number 040001
city: Brasilia
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076001
city: Curitiba
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076003
city: Fortaleza
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076005
city: Fortaleza
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076004
city: Porto Alegre
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076002
city: Rio De Janeiro
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076006
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152002
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152003
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152001
city: Viña Del Mar
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152004
city: Olomouc
country: Czech Republic
facility: Sanofi-Aventis Investigational Site Number 203001
city: Pardubice
country: Czech Republic
facility: Sanofi-Aventis Investigational Site Number 203003
city: Usti Nad Labem
country: Czech Republic
facility: Sanofi-Aventis Investigational Site Number 203002
city: Düsseldorf
country: Germany
facility: Sanofi-Aventis Investigational Site Number 276002
city: Münster
country: Germany
facility: Sanofi-Aventis Investigational Site Number 276003
city: Budapest
country: Hungary
facility: Sanofi-Aventis Investigational Site Number 348004
city: Budapest
country: Hungary
facility: Sanofi-Aventis Investigational Site Number 348005
city: Miskolc
country: Hungary
facility: Sanofi-Aventis Investigational Site Number 348003
city: Szeged
country: Hungary
facility: Sanofi-Aventis Investigational Site Number 348002
city: Szombathely
country: Hungary
facility: Sanofi-Aventis Investigational Site Number 348001
city: Bangalore
country: India
facility: Sanofi-Aventis Investigational Site Number 356003
city: Bangalore
country: India
facility: Sanofi-Aventis Investigational Site Number 356005
city: Bangalore
country: India
facility: Sanofi-Aventis Investigational Site Number 356001
city: Indore
country: India
facility: Sanofi-Aventis Investigational Site Number 356002
city: Karnal
country: India
facility: Sanofi-Aventis Investigational Site Number 356004
city: Guadalajara
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484002
city: Monterrey
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484003
city: Puebla
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484001
city: Lima
country: Peru
facility: Sanofi-Aventis Investigational Site Number 604003
city: Lima
country: Peru
facility: Sanofi-Aventis Investigational Site Number 604002
city: Lima
country: Peru
facility: Sanofi-Aventis Investigational Site Number 604001
city: Gdansk
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616002
city: Warszawa
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616001
city: Bucharest
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642008
city: Cluj Napoca
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642001
city: Constanta
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642011
city: Sibiu
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642006
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis Investigational Site Number 643001
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis Investigational Site Number 643002
city: St-Petersburg
country: Russian Federation
facility: Sanofi-Aventis Investigational Site Number 643003
city: Ufa
country: Russian Federation
facility: Sanofi-Aventis Investigational Site Number 643004
city: Yaroslavl
country: Russian Federation
facility: Sanofi-Aventis Investigational Site Number 643005
city: Durban
country: South Africa
facility: Sanofi-Aventis Investigational Site Number 710004
city: Johannesburg
country: South Africa
facility: Sanofi-Aventis Investigational Site Number 710002
city: Observatory
country: South Africa
facility: Sanofi-Aventis Investigational Site Number 710001
city: Pretoria
country: South Africa
facility: Sanofi-Aventis Investigational Site Number 710003
city: Santiago De Compostela
country: Spain
facility: Sanofi-Aventis Investigational Site Number 724003
city: Sevilla
country: Spain
facility: Sanofi-Aventis Investigational Site Number 724001
city: Valencia
country: Spain
facility: Sanofi-Aventis Investigational Site Number 724005
city: Zaragoza
country: Spain
facility: Sanofi-Aventis Investigational Site Number 724004
city: Ankara
country: Turkey
facility: Sanofi-Aventis Investigational Site Number 792001
city: Istanbul
country: Turkey
facility: Sanofi-Aventis Investigational Site Number 792003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Danne T, Becker RH, Ping L, Philotheou A. Insulin glargine metabolite 21(A) -Gly-human insulin (M1) is the principal component circulating in the plasma of young children with type 1 diabetes: results from the PRESCHOOL study. Pediatr Diabetes. 2015 Jun;16(4):299-304. doi: 10.1111/pedi.12161. Epub 2014 Jul 9.