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

Type 1 Diabetes Mellitus Clinical Trial

— PRESCHOOL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00993473
• Other study ID #: EFC11202
• Secondary ID: 2009-011231-12
• Status: Completed
• Phase: Phase 3
• First received: October 9, 2009
• Last updated: June 25, 2012
• Start date: October 2009
• Est. completion date: March 2011

Study information

• Verified date: June 2012
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 6 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

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%.
• 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
• 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.

Locations

Country	Name	City	State
Austria	Sanofi-Aventis Investigational Site Number 040001	Wien
Brazil	Sanofi-Aventis Investigational Site Number 076001	Brasilia
Brazil	Sanofi-Aventis Investigational Site Number 076003	Curitiba
Brazil	Sanofi-Aventis Investigational Site Number 076004	Fortaleza
Brazil	Sanofi-Aventis Investigational Site Number 076005	Fortaleza
Brazil	Sanofi-Aventis Investigational Site Number 076002	Porto Alegre
Brazil	Sanofi-Aventis Investigational Site Number 076006	Rio De Janeiro
Chile	Sanofi-Aventis Investigational Site Number 152001	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152002	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152003	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152004	Viña Del Mar
Czech Republic	Sanofi-Aventis Investigational Site Number 203001	Olomouc
Czech Republic	Sanofi-Aventis Investigational Site Number 203003	Pardubice
Czech Republic	Sanofi-Aventis Investigational Site Number 203002	Usti Nad Labem
Germany	Sanofi-Aventis Investigational Site Number 276002	Düsseldorf
Germany	Sanofi-Aventis Investigational Site Number 276003	Münster
Hungary	Sanofi-Aventis Investigational Site Number 348004	Budapest
Hungary	Sanofi-Aventis Investigational Site Number 348005	Budapest
Hungary	Sanofi-Aventis Investigational Site Number 348003	Miskolc
Hungary	Sanofi-Aventis Investigational Site Number 348002	Szeged
Hungary	Sanofi-Aventis Investigational Site Number 348001	Szombathely
India	Sanofi-Aventis Investigational Site Number 356001	Bangalore
India	Sanofi-Aventis Investigational Site Number 356003	Bangalore
India	Sanofi-Aventis Investigational Site Number 356005	Bangalore
India	Sanofi-Aventis Investigational Site Number 356002	Indore
India	Sanofi-Aventis Investigational Site Number 356004	Karnal
Mexico	Sanofi-Aventis Investigational Site Number 484002	Guadalajara
Mexico	Sanofi-Aventis Investigational Site Number 484003	Monterrey
Mexico	Sanofi-Aventis Investigational Site Number 484001	Puebla
Peru	Sanofi-Aventis Investigational Site Number 604001	Lima
Peru	Sanofi-Aventis Investigational Site Number 604002	Lima
Peru	Sanofi-Aventis Investigational Site Number 604003	Lima
Poland	Sanofi-Aventis Investigational Site Number 616002	Gdansk
Poland	Sanofi-Aventis Investigational Site Number 616001	Warszawa
Romania	Sanofi-Aventis Investigational Site Number 642008	Bucharest
Romania	Sanofi-Aventis Investigational Site Number 642001	Cluj Napoca
Romania	Sanofi-Aventis Investigational Site Number 642011	Constanta
Romania	Sanofi-Aventis Investigational Site Number 642006	Sibiu
Russian Federation	Sanofi-Aventis Investigational Site Number 643001	Moscow
Russian Federation	Sanofi-Aventis Investigational Site Number 643002	Moscow
Russian Federation	Sanofi-Aventis Investigational Site Number 643003	St-Petersburg
Russian Federation	Sanofi-Aventis Investigational Site Number 643004	Ufa
Russian Federation	Sanofi-Aventis Investigational Site Number 643005	Yaroslavl
South Africa	Sanofi-Aventis Investigational Site Number 710004	Durban
South Africa	Sanofi-Aventis Investigational Site Number 710002	Johannesburg
South Africa	Sanofi-Aventis Investigational Site Number 710001	Observatory
South Africa	Sanofi-Aventis Investigational Site Number 710003	Pretoria
Spain	Sanofi-Aventis Investigational Site Number 724003	Santiago De Compostela
Spain	Sanofi-Aventis Investigational Site Number 724001	Sevilla
Spain	Sanofi-Aventis Investigational Site Number 724005	Valencia
Spain	Sanofi-Aventis Investigational Site Number 724004	Zaragoza
Turkey	Sanofi-Aventis Investigational Site Number 792001	Ankara
Turkey	Sanofi-Aventis Investigational Site Number 792003	Istanbul
United States	Sanofi-Aventis Investigational Site Number 840008	Baltimore	Maryland
United States	Sanofi-Aventis Investigational Site Number 840007	Buffalo	New York
United States	Sanofi-Aventis Investigational Site Number 840005	Greenwood Village	Colorado
United States	Sanofi-Aventis Investigational Site Number 840010	Houston	Texas
United States	Sanofi-Aventis Investigational Site Number 840011	Philadelphia	Pennsylvania
United States	Sanofi-Aventis Investigational Site Number 840006	Sacramento	California
United States	Sanofi-Aventis Investigational Site Number 840002	San Antonio	Texas
United States	Sanofi-Aventis Investigational Site Number 840014	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Austria,  Brazil,  Chile,  Czech Republic,  Germany,  Hungary,  India,  Mexico,  Peru,  Poland,  Romania,  Russian Federation,  South Africa,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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.	6 months	Yes
Secondary	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)	Symptomatic hypoglycemia: any event with clinical symptoms considered to result from hypoglycemia, validated by the study investigator based on data from patient diaries.	6 months	Yes
Secondary	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	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.	6 months	Yes
Secondary	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	Nocturnal hypoglycemia: any event from the "all hypoglycemia" total that occurred between 23:00 and 07:00 hours.	6 months	Yes
Secondary	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	Nocturnal symptomatic hypoglycemia: any symptomatic hypoglycemic event that occurred between 23:00 and 07:00 hours.	6 months	Yes
Secondary	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	Severe nocturnal symptomatic hypoglycemia: any severe symptomatic hypoglycemic event that occurred between 23:00 and 07:00 hours.	6 months	Yes
Secondary	Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment		baseline, 6 months	No
Secondary	Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment (ANCOVA Estimates)	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.	baseline, 6 months	No
Secondary	Percentage of Patients Reaching HbA1c Target of Less Than 7.5% at the End of Treatment Visit	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.	6 months	No
Secondary	Average Daily Blood Glucose (BG) Based on CGMS Values: End of Treatment and Change From Baseline to End of Treatment		baseline, 6 months	No