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

Phase 3

Completed

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Drug: Insulin glargine (HOE901); Drug: Neutral Protamine Hagedorn (NPH) insulin; Drug: Insulin lispro

• Registration Number: NCT00993473
• Lead Sponsor: Sanofi

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

Study Timeline

• Study Start: 2009-10
• Study First Submitted: 2009-10-09
• Study First Submitted QC: 2009-10-09
• Study First Posted: 2009-10-12
• Primary Completion: 2011-03
• Study Completion: 2011-03
• Results First Submitted: 2012-03-28
• Results First Submitted QC: 2012-05-16
• Status Verified: 2012-06
• Results First Posted: 2012-06-22
• Last Update Submitted: 2012-06-25
• Last Update Posted: 2012-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 125

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lantus (insulin glargine)	Insulin glargine (HOE901)	Lantus given as basal insulin once a day in the morning by subcutaneous injection
Lantus (insulin glargine)	Insulin lispro	Lantus given as basal insulin once a day in the morning by subcutaneous injection
NPH insulin	Insulin lispro	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
NPH insulin	Neutral Protamine Hagedorn (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

Primary Outcome Measures

Name	Time	Method
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)	6 months	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

Name	Time	Method
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	6 months	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 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)	6 months	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 Nocturnal Hypoglycemia Defined as the Total Number of "All Hypoglycemia" Episodes Divided by the Total Duration of the On-treatment Period in Years	6 months	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	6 months	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	6 months	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	baseline, 6 months
Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment (ANCOVA Estimates)	baseline, 6 months	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	6 months	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	baseline, 6 months

Trial Locations

Locations (61)

Sanofi-Aventis Investigational Site Number 356001; 🇮🇳 Bangalore, India

Sanofi-Aventis Investigational Site Number 356004; 🇮🇳 Karnal, India

Sanofi-Aventis Investigational Site Number 484003; 🇲🇽 Monterrey, Mexico

Sanofi-Aventis Investigational Site Number 604002; 🇵🇪 Lima, Peru

Sanofi-Aventis Investigational Site Number 276002; 🇩🇪 Düsseldorf, Germany

Sanofi-Aventis Investigational Site Number 152002; 🇨🇱 Santiago, Chile

Sanofi-Aventis Investigational Site Number 840010; 🇺🇸 Houston, Texas, United States

Sanofi-Aventis Investigational Site Number 840007; 🇺🇸 Buffalo, New York, United States

Sanofi-Aventis Investigational Site Number 040001; 🇦🇹 Wien, Austria

Sanofi-Aventis Investigational Site Number 152004; 🇨🇱 Viña Del Mar, Chile

Sanofi-Aventis Investigational Site Number 348002; 🇭🇺 Szeged, Hungary

Sanofi-Aventis Investigational Site Number 076005; 🇧🇷 Fortaleza, Brazil

Sanofi-Aventis Investigational Site Number 643003; 🇷🇺 St-Petersburg, Russian Federation

Sanofi-Aventis Investigational Site Number 348004; 🇭🇺 Budapest, Hungary

Sanofi-Aventis Investigational Site Number 152003; 🇨🇱 Santiago, Chile

Sanofi-Aventis Investigational Site Number 348003; 🇭🇺 Miskolc, Hungary

Sanofi-Aventis Investigational Site Number 348001; 🇭🇺 Szombathely, Hungary

Sanofi-Aventis Investigational Site Number 356003; 🇮🇳 Bangalore, India

Sanofi-Aventis Investigational Site Number 604001; 🇵🇪 Lima, Peru

Sanofi-Aventis Investigational Site Number 616002; 🇵🇱 Gdansk, Poland

Sanofi-Aventis Investigational Site Number 792001; 🇹🇷 Ankara, Turkey

Sanofi-Aventis Investigational Site Number 076006; 🇧🇷 Rio De Janeiro, Brazil

Sanofi-Aventis Investigational Site Number 643004; 🇷🇺 Ufa, Russian Federation

Sanofi-Aventis Investigational Site Number 604003; 🇵🇪 Lima, Peru

Sanofi-Aventis Investigational Site Number 724005; 🇪🇸 Valencia, Spain

Sanofi-Aventis Investigational Site Number 710003; 🇿🇦 Pretoria, South Africa

Sanofi-Aventis Investigational Site Number 724004; 🇪🇸 Zaragoza, Spain

Sanofi-Aventis Investigational Site Number 484002; 🇲🇽 Guadalajara, Mexico

Sanofi-Aventis Investigational Site Number 643005; 🇷🇺 Yaroslavl, Russian Federation

Sanofi-Aventis Investigational Site Number 724001; 🇪🇸 Sevilla, Spain

Sanofi-Aventis Investigational Site Number 710002; 🇿🇦 Johannesburg, South Africa

Sanofi-Aventis Investigational Site Number 203002; 🇨🇿 Usti Nad Labem, Czech Republic

Sanofi-Aventis Investigational Site Number 642001; 🇷🇴 Cluj Napoca, Romania

Sanofi-Aventis Investigational Site Number 356005; 🇮🇳 Bangalore, India

Sanofi-Aventis Investigational Site Number 484001; 🇲🇽 Puebla, Mexico

Sanofi-Aventis Investigational Site Number 642008; 🇷🇴 Bucharest, Romania

Sanofi-Aventis Investigational Site Number 642011; 🇷🇴 Constanta, Romania

Sanofi-Aventis Investigational Site Number 642006; 🇷🇴 Sibiu, Romania

Sanofi-Aventis Investigational Site Number 643002; 🇷🇺 Moscow, Russian Federation

Sanofi-Aventis Investigational Site Number 840006; 🇺🇸 Sacramento, California, United States

Sanofi-Aventis Investigational Site Number 840008; 🇺🇸 Baltimore, Maryland, United States

Sanofi-Aventis Investigational Site Number 840014; 🇺🇸 San Diego, California, United States

Sanofi-Aventis Investigational Site Number 840011; 🇺🇸 Philadelphia, Pennsylvania, United States

Sanofi-Aventis Investigational Site Number 840005; 🇺🇸 Greenwood Village, Colorado, United States

Sanofi-Aventis Investigational Site Number 076001; 🇧🇷 Brasilia, Brazil

Sanofi-Aventis Investigational Site Number 076002; 🇧🇷 Porto Alegre, Brazil

Sanofi-Aventis Investigational Site Number 076004; 🇧🇷 Fortaleza, Brazil

Sanofi-Aventis Investigational Site Number 152001; 🇨🇱 Santiago, Chile

Sanofi-Aventis Investigational Site Number 203001; 🇨🇿 Olomouc, Czech Republic

Sanofi-Aventis Investigational Site Number 203003; 🇨🇿 Pardubice, Czech Republic

Sanofi-Aventis Investigational Site Number 276003; 🇩🇪 Münster, Germany

Sanofi-Aventis Investigational Site Number 348005; 🇭🇺 Budapest, Hungary

Sanofi-Aventis Investigational Site Number 356002; 🇮🇳 Indore, India

Sanofi-Aventis Investigational Site Number 616001; 🇵🇱 Warszawa, Poland

Sanofi-Aventis Investigational Site Number 643001; 🇷🇺 Moscow, Russian Federation

Sanofi-Aventis Investigational Site Number 724003; 🇪🇸 Santiago De Compostela, Spain

Sanofi-Aventis Investigational Site Number 710001; 🇿🇦 Observatory, South Africa

Sanofi-Aventis Investigational Site Number 710004; 🇿🇦 Durban, South Africa

Sanofi-Aventis Investigational Site Number 792003; 🇹🇷 Istanbul, Turkey

Sanofi-Aventis Investigational Site Number 840002; 🇺🇸 San Antonio, Texas, United States

Sanofi-Aventis Investigational Site Number 076003; 🇧🇷 Curitiba, Brazil