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

NCT ID: NCT00993473

Last Updated: 2012-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2011-03-31

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

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lantus (insulin glargine)

Lantus given as basal insulin once a day in the morning by subcutaneous injection

Group Type: EXPERIMENTAL

Insulin glargine (HOE901)

Intervention Type: DRUG

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%.

Insulin lispro

Intervention Type: DRUG

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.

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

Group Type: ACTIVE_COMPARATOR

Neutral Protamine Hagedorn (NPH) insulin

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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%.

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Lantus®; Humalog®

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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Investigational Site Number 840006

Sacramento, California, United States

Sanofi-Aventis Investigational Site Number 840014

San Diego, California, United States

Sanofi-Aventis Investigational Site Number 840005

Greenwood Village, Colorado, 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 840011

Philadelphia, Pennsylvania, United States

Sanofi-Aventis Investigational Site Number 840010

Houston, Texas, United States

Sanofi-Aventis Investigational Site Number 840002

San Antonio, Texas, United States

Sanofi-Aventis Investigational Site Number 040001

Vienna, , Austria

Sanofi-Aventis Investigational Site Number 076001

Brasília, , Brazil

Sanofi-Aventis Investigational Site Number 076003

Curitiba, , Brazil

Sanofi-Aventis Investigational Site Number 076005

Fortaleza, , Brazil

Sanofi-Aventis Investigational Site Number 076004

Fortaleza, , Brazil

Sanofi-Aventis Investigational Site Number 076002

Porto Alegre, , Brazil

Sanofi-Aventis Investigational Site Number 076006

Rio de Janeiro, , Brazil

Sanofi-Aventis Investigational Site Number 152002

Santiago, , Chile

Sanofi-Aventis Investigational Site Number 152003

Santiago, , Chile

Sanofi-Aventis Investigational Site Number 152001

Santiago, , Chile

Sanofi-Aventis Investigational Site Number 152004

Viña del Mar, , Chile

Sanofi-Aventis Investigational Site Number 203001

Olomouc, , Czechia

Sanofi-Aventis Investigational Site Number 203003

Pardubice, , Czechia

Sanofi-Aventis Investigational Site Number 203002

Ústí nad Labem, , Czechia

Sanofi-Aventis Investigational Site Number 276002

Düsseldorf, , Germany

Sanofi-Aventis Investigational Site Number 276003

Münster, , Germany

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, , Hungary

Sanofi-Aventis Investigational Site Number 356003

Bangalore, , India

Sanofi-Aventis Investigational Site Number 356005

Bangalore, , India

Sanofi-Aventis Investigational Site Number 356001

Bangalore, , India

Sanofi-Aventis Investigational Site Number 356002

Indore, , India

Sanofi-Aventis Investigational Site Number 356004

Karnāl, , India

Sanofi-Aventis Investigational Site Number 484002

Guadalajara, , Mexico

Sanofi-Aventis Investigational Site Number 484003

Monterrey, , Mexico

Sanofi-Aventis Investigational Site Number 484001

Puebla City, , Mexico

Sanofi-Aventis Investigational Site Number 604003

Lima, , Peru

Sanofi-Aventis Investigational Site Number 604002

Lima, , Peru

Sanofi-Aventis Investigational Site Number 604001

Lima, , Peru

Sanofi-Aventis Investigational Site Number 616002

Gdansk, , Poland

Sanofi-Aventis Investigational Site Number 616001

Warsaw, , Poland

Sanofi-Aventis Investigational Site Number 642008

Bucharest, , Romania

Sanofi-Aventis Investigational Site Number 642001

Cluj-Napoca, , Romania

Sanofi-Aventis Investigational Site Number 642011

Constanța, , Romania

Sanofi-Aventis Investigational Site Number 642006

Sibiu, , Romania

Sanofi-Aventis Investigational Site Number 643001

Moscow, , Russia

Sanofi-Aventis Investigational Site Number 643002

Moscow, , Russia

Sanofi-Aventis Investigational Site Number 643003

Saint Petersburg, , Russia

Sanofi-Aventis Investigational Site Number 643004

Ufa, , Russia

Sanofi-Aventis Investigational Site Number 643005

Yaroslavl, , Russia

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, , South Africa

Sanofi-Aventis Investigational Site Number 724003

Santiago de Compostela, , Spain

Sanofi-Aventis Investigational Site Number 724001

Seville, , Spain

Sanofi-Aventis Investigational Site Number 724005

Valencia, , Spain

Sanofi-Aventis Investigational Site Number 724004

Zaragoza, , Spain

Sanofi-Aventis Investigational Site Number 792001

Ankara, , Turkey (Türkiye)

Sanofi-Aventis Investigational Site Number 792003

Istanbul, , Turkey (Türkiye)

Countries

United States; Austria; Brazil; Chile; Czechia; Germany; Hungary; India; Mexico; Peru; Poland; Romania; Russia; South Africa; Spain; Turkey (Türkiye)

References

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.

Reference Type: DERIVED

PMID: 25041275 (View on PubMed)

Other Identifiers

2009-011231-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC11202

Identifier Type: -

Identifier Source: org_study_id