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

NCT00993473 | Completed Phase 3 Results

• 2 other identifiers: EFC112022009-011231-12
• Study Type: interventional
• Target: 125
• Locations: 16 countries
• Sites: 61

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

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (9)

• 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

• 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

• 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

• 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

• 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

Other Outcomes (4)

• Number of Patients With Different Types of Hypoglycemia Events

  6 months

• Percent of Blood Glucose (BG) Within the Range of 70 - 180 mg/dL (3.9-10 mmol/L)

  6 months

• Blood Glucose Variability Based on All On-treatment CGMS Values

  6 months

Study Arms (2)

Lantus (insulin glargine)

EXPERIMENTAL

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

Drug: Insulin glargine (HOE901); Drug: Insulin lispro

NPH insulin

ACTIVE COMPARATOR

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

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

Interventions

Insulin glargine (HOE901) 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%.

Also known as: Lantus®

Lantus (insulin glargine)

Neutral Protamine Hagedorn (NPH) insulin 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

NPH insulin

Insulin lispro 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.

Also known as: Humalog®

Lantus (insulin glargine); NPH insulin

Eligibility Criteria

• Age: 1 Year - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (61)

Sanofi-Aventis Investigational Site Number 840006

Sacramento, California, 95819, United States

Location

Sanofi-Aventis Investigational Site Number 840014

San Diego, California, 92123, United States

Location

Sanofi-Aventis Investigational Site Number 840005

Greenwood Village, Colorado, 80111, United States

Location

Sanofi-Aventis Investigational Site Number 840008

Baltimore, Maryland, 21229, United States

Location

Sanofi-Aventis Investigational Site Number 840007

Buffalo, New York, 14222, United States

Location

Sanofi-Aventis Investigational Site Number 840011

Philadelphia, Pennsylvania, 19104, United States

Location

Sanofi-Aventis Investigational Site Number 840010

Houston, Texas, 77030, United States

Location

Sanofi-Aventis Investigational Site Number 840002

San Antonio, Texas, 78229, United States

Location

Sanofi-Aventis Investigational Site Number 040001

Vienna, 1090, Austria

Location

Sanofi-Aventis Investigational Site Number 076001

Brasília, 71625-009, Brazil

Location

Sanofi-Aventis Investigational Site Number 076003

Curitiba, 80810-040, Brazil

Location

Sanofi-Aventis Investigational Site Number 076005

Fortaleza, 60135-170, Brazil

Location

Sanofi-Aventis Investigational Site Number 076004

Fortaleza, 60430-370, Brazil

Location

Sanofi-Aventis Investigational Site Number 076002

Porto Alegre, 91350-250, Brazil

Location

Sanofi-Aventis Investigational Site Number 076006

Rio de Janeiro, 20211-340, Brazil

Location

Sanofi-Aventis Investigational Site Number 152002

Santiago, 7830489, Chile

Location

Sanofi-Aventis Investigational Site Number 152003

Santiago, 8207257, Chile

Location

Sanofi-Aventis Investigational Site Number 152001

Santiago, 8910095, Chile

Location

Sanofi-Aventis Investigational Site Number 152004

Viña del Mar, 257-0017, Chile

Location

Sanofi-Aventis Investigational Site Number 203001

Olomouc, 77520, Czechia

Location

Sanofi-Aventis Investigational Site Number 203003

Pardubice, 53203, Czechia

Location

Sanofi-Aventis Investigational Site Number 203002

Ústí nad Labem, 40113, Czechia

Location

Sanofi-Aventis Investigational Site Number 276002

Düsseldorf, 40225, Germany

Location

Sanofi-Aventis Investigational Site Number 276003

Münster, 48155, Germany

Location

Sanofi-Aventis Investigational Site Number 348004

Budapest, 1023, Hungary

Location

Sanofi-Aventis Investigational Site Number 348005

Budapest, 1089, Hungary

Location

Sanofi-Aventis Investigational Site Number 348003

Miskolc, 3526, Hungary

Location

Sanofi-Aventis Investigational Site Number 348002

Szeged, 6701, Hungary

Location

Sanofi-Aventis Investigational Site Number 348001

Szombathely, 9700, Hungary

Location

Sanofi-Aventis Investigational Site Number 356003

Bangalore, 560043, India

Location

Sanofi-Aventis Investigational Site Number 356005

Bangalore, 560052, India

Location

Sanofi-Aventis Investigational Site Number 356001

Bangalore, India

Location

Sanofi-Aventis Investigational Site Number 356002

Indore, 452001, India

Location

Sanofi-Aventis Investigational Site Number 356004

Karnāl, 132001, India

Location

Sanofi-Aventis Investigational Site Number 484002

Guadalajara, 44620, Mexico

Location

Sanofi-Aventis Investigational Site Number 484003

Monterrey, 64640, Mexico

Location

Sanofi-Aventis Investigational Site Number 484001

Puebla City, 72190, Mexico

Location

Sanofi-Aventis Investigational Site Number 604003

Lima, Lima 01, Peru

Location

Sanofi-Aventis Investigational Site Number 604002

Lima, Lima 5, Peru

Location

Sanofi-Aventis Investigational Site Number 604001

Lima, Peru

Location

Sanofi-Aventis Investigational Site Number 616002

Gdansk, Poland

Location

Sanofi-Aventis Investigational Site Number 616001

Warsaw, 04-730, Poland

Location

Sanofi-Aventis Investigational Site Number 642008

Bucharest, 041451, Romania

Location

Sanofi-Aventis Investigational Site Number 642001

Cluj-Napoca, 400370, Romania

Location

Sanofi-Aventis Investigational Site Number 642011

Constanța, 900591, Romania

Location

Sanofi-Aventis Investigational Site Number 642006

Sibiu, 550166, Romania

Location

Sanofi-Aventis Investigational Site Number 643001

Moscow, 117036, Russia

Location

Sanofi-Aventis Investigational Site Number 643002

Moscow, 119049, Russia

Location

Sanofi-Aventis Investigational Site Number 643003

Saint Petersburg, 193144, Russia

Location

Sanofi-Aventis Investigational Site Number 643004

Ufa, 450000, Russia

Location

Sanofi-Aventis Investigational Site Number 643005

Yaroslavl, 150042, Russia

Location

Sanofi-Aventis Investigational Site Number 710004

Durban, South Africa

Location

Sanofi-Aventis Investigational Site Number 710002

Johannesburg, 2193, South Africa

Location

Sanofi-Aventis Investigational Site Number 710001

Observatory, 7925, South Africa

Location

Sanofi-Aventis Investigational Site Number 710003

Pretoria, 0084, South Africa

Location

Sanofi-Aventis Investigational Site Number 724003

Santiago de Compostela, 15706, Spain

Location

Sanofi-Aventis Investigational Site Number 724001

Seville, 41013, Spain

Location

Sanofi-Aventis Investigational Site Number 724005

Valencia, 46010, Spain

Location

Sanofi-Aventis Investigational Site Number 724004

Zaragoza, 50009, Spain

Location

Sanofi-Aventis Investigational Site Number 792001

Ankara, 06100, Turkey (Türkiye)

Location

Sanofi-Aventis Investigational Site Number 792003

Istanbul, 34000, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 25041275 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin Glargine; Insulin; Insulin Lispro

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Proinsulin; Insulin, Short-Acting

Limitations and Caveats

There are numerous potential biases that could affect the timing and frequency of performance of sporadic FSBG, such as mealtime dosing and choice of bolus insulin dose, stability and familiarity with insulin regimens, and parental anxiety levels.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: sanofi-aventis

Contact_US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2009
• First Posted: October 12, 2009
• Study Start: October 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: June 27, 2012
• Results First Posted: June 22, 2012

Record last verified: 2012-06

Locations

TU (2); US (8); ME (3); HU (5); RO (4); ZA (4); PE (3); ES (4); CL (4); IN (5); AU (1); DE (2); BR (6); CZ (3); PL (2); RU (5)