Comparison of the Ability of Glulisine With Lispro to Control Type 1 Diabetes Mellitus in Children and Adolescents

Efficacy and Safety of Insulin Glulisine Compared With Insulin Lispro in Children and Adolescents With Type 1 Diabetes Mellitus: A 26 Week, Multicenter, Open, Parallel Clinical Trial

The purpose of this study is to determine if insulin glulisine (Apidra) is as safe and effective a rapid acting insulin as insulin lispro (Humalog) in children and adolescents with type 1 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Insulin-Dependent
• Intervention / Treatment: Drug: Insulin glulisine; Drug: insulin glargine; Drug: NPH insulin; Drug: insulin lispro

• Study Type: Interventional
• Enrollment (Actual): 572
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Childrens Hospital of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Girls/boys, 4-17 years, inclusive;
• Girls not yet of childbearing potential or, if sexually active, agree to use reliable medically accepted contraceptive measure during study;
• Type 1 diabetes mellitus established in medical history: for example, but not limited to, clear signs of insulinopenia (polyuria, polydipsia, polyphagia, weight loss, ketonuria, ketoacidosis); or glutamic acid decarboxylase (GAD) antibody indicative of type 1 diabetes measured at any time before study; or requiring continuous insulin therapy from time of diagnosis;
• Onset of diabetes at least 1 year prior to visit 1 (V1) of study;
• Uninterrupted insulin therapy for at least 1 year before V1 of study;
• At V1, on stable insulin regimen of either NPH or insulin glargine as basal insulin and willing to have multiple daily injections of insulin;
• Glycated hemoglobin at V1 between ≥ 6.0 and ≤11.0 %;
• Ability/willingness to do blood glucose monitoring using sponsor-provided glucometer and subject diary.

Exclusion Criteria:

• Active proliferative diabetic retinopathy, defined by application of focal or panretinal photocoagulation or vitrectomy, 6 months before V1, or any other unstable/rapidly progressing retinopathy requiring surgical treatment (including laser photocoagulation) during study;
• Diabetes other than type 1 diabetes mellitus;
• Pregnancy (positive pregnancy blood test at V1) or breastfeeding;
• Pancreatectomized subjects;
• Subjects who have had pancreas and/or islet cell transplants;
• Treatment with any anti-diabetic oral agent at any time from diabetes diagnosis;
• Treatment with systemic corticosteroids in last month before V1;
• Subjects on pump therapy during last 2 months before V1;
• Subjects requiring excessively high doses of insulin ("resistant" patients), for example, but not limited to, subjects receiving over 150 IU per day;
• Likelihood of needing treatment during study period with drugs not permitted by protocol
• Treatment with any investigational drug in last month before V1;
• History of primary seizure disorders;
• History of severe hypoglycemic episode accompanied by seizure and/or coma or diabetic ketoacidosis leading to hospitalization, or to care in emergency ward, 3 months prior to V1;
• History of hypoglycemia unawareness;
• History of hypersensitivity to insulin or insulin analogs or any of the excipients in insulin glulisine formulation or any of the excipients in other study insulin preparations formulations;
• Clinically relevant hepatic, neurologic, endocrine, active cancer, or other major systemic disease making implementation of protocol or interpretation of study results difficult and would, in the opinion of the investigator, preclude safe participation of subject in protocol;
• History of cardiac abnormalities and/or cardiovascular disorders;
• History of drug/alcohol abuse;
• Impaired hepatic function shown by, but not limited to, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than twice the normal upper limit for age at V1;
• Impaired renal function shown by, but not limited to, serum creatinine greater than 1.5 times upper limit for age at V1;
• Non fasting triglyceride level of >500 mg/dL (5.7 mmol/L) at V1;
• Parent/legally authorized representative unable to understand nature, scope, possible consequences of study;
• Parent/legally authorized representative unable to read/write;
• Subjects unlikely to comply with protocol, e.g. inability/unwillingness to participate in adequate training, uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing study;
• Children/relatives of employee of sponsor or of sponsor representatives;
• Children or relatives of investigator, any sub-investigator, research assistant, pharmacist, study coordinator or other staff directly involved in conduct of protocol;
• Subjects who have previously been treated with insulin glulisine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Insulin Glulisine; Insulin Glulisine (100UI/ml), at least twice daily, in association with basal insulin therapy (NPH insulin or insulin glargine for a maximum of 26 weeks	Drug: Insulin glulisine; Subcutaneous injection; Other Names: apidra; Drug: insulin glargine; Subcutaneous injection once daily; Drug: NPH insulin; subcutaneous injection twice daily
ACTIVE_COMPARATOR: Insulin Lispro; Insulin Lispro (100UI/ml) Subcutaneous (SC) injection , at least twice daily, in association with basal insulin therapy (NPH insulin or insulin glargine ) for a maximum of 30 weeks	Drug: insulin glargine; Subcutaneous injection once daily; Drug: NPH insulin; subcutaneous injection twice daily; Drug: insulin lispro; Subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in total glycated hemoglobin measured as HbA1c equivalents (GHb )from baseline to endpoint	week 26 or last observed treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in GHb at weeks 12 and 26	weeks 12 and 26
Change from Baseline in Self-monitored glucose parameters	weeks 4, 12, 18, 26, and endpoint;
Incidence of Symptomatic hypoglycemia	first dose of study up to last dose
Change from Baseline in basal insulin dose	week 4, 12, 18, 26, and endpoint;

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Principal Investigator: Dr Arethi PHILOTHEOU, UCT Diabetes Clinical Trials Unit - Faculty of Health Sciences - South-Africa

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (ACTUAL): November 1, 2006
• Study Completion (ACTUAL): November 1, 2006

Study Registration Dates

• First Submitted: June 23, 2005
• First Submitted That Met QC Criteria: June 23, 2005
• First Posted (ESTIMATE): June 24, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): May 20, 2016
• Last Update Submitted That Met QC Criteria: May 19, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Diabetes,Insulin-Dependent, pediatric,rapid acting injection
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Lispro; Insulin glulisine; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef
• Other Study ID Numbers: EFC6096; HMR 1964