Comparison of Insulin Detemir and Insulin Aspart in 2 Separate Injections Twice Daily to Extemporaneous Mixing Injection Regimen Twice Daily - The Paediatric Mixing Trial (MIXING)

A Randomised, Multicentric, Open Labelled, Parallel Group Trial With Insulin Aspart and Insulin Detemir, Investigating the Glycaemic Effect and Profile in Children With Type 1 Diabetes, of Two Separate Levemir® + NovoRapid® Injections and Extemporaneous Mixing - The Paediatric MIXING Trial

This trial is conducted in Europe. The aim of the trial is to compare two methods of injection in basal-bolus insulin regimen in children with type 1 diabetes with insulin detemir associated with insulin aspart given twice daily in either separate or mixed injections and to investigate if there is any clinical impact in choosing one regimen over another.

Study Overview

• Status: Completed
• Conditions: Diabetes; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: insulin detemir; Drug: insulin aspart; Drug: insulin detemir; Drug: insulin aspart

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Paris, France

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Parents' Informed Consent (IC) obtained before any trial-related activities
• Obtained child's assent (when possible)
• Type 1 diabetes
• Treatment with insulin detemir and insulin aspart either in extemporaneous mixed or separate injections
• HbA1c (glycosylated haemoglobin A1c) lesser than or equal to 8.6%

Exclusion Criteria:

• History of alcoholism, drug abuse, or psychiatric disease or personality disorders likely to invalidate voluntary consent or to prevent good compliance with the trial protocol
• Mental incapacity, unwillingness or language barrier precluding adequate understanding or co-operation
• Anticipated change or new use in concomitant medication known to interfere with glucose metabolism, such as systemic corticotherapy more than 5 mg/day (prednisone)
• Any other condition that the Investigator (trial physician) feels would interfere with trial participation or evaluation of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mixed injection	Drug: insulin detemir; Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, mixed with insulin aspart; Drug: insulin aspart; Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, mixed with insulin detemir; Drug: insulin detemir; Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, injected separately with insulin aspart; Drug: insulin aspart; Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, injected separately with insulin detemir
Active Comparator: Separate injection	Drug: insulin detemir; Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, mixed with insulin aspart; Drug: insulin aspart; Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, mixed with insulin detemir; Drug: insulin detemir; Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, injected separately with insulin aspart; Drug: insulin aspart; Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, injected separately with insulin detemir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycosylated Haemoglobin A1c (HbA1c)	Measured for the Per Protocol (PP) set	Week 0 and Week 8
Glycosylated Haemoglobin A1c (HbA1c)	Measured for the ITT (Intention-to-Treat) set	Week 0 and Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fructosamine		Week 0 and Week 8
Self-measured Plasma Glucose Profile (Before Breakfast)		Week 0 and Week 8
Self-measured Plasma Glucose Profile (After Breakfast)		Week 0 and Week 8
Self-measured Plasma Glucose Profile (Before Dinner)		Week 0 and Week 8
Self-measured Plasma Glucose Profile (After Dinner)		Week 0 and Week 8
Pharmacokinetics: Cmax of Free Insulin	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2 hours (hrs), T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Tmax of Free Insulin	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Free Insulin	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Free Insulin	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Free Insulin	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Cmax of Insulin Detemir	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Tmax of Insulin Detemir	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Detemir	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Detemir	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Detemir	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Cmax of Insulin Aspart	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Tmax of Insulin Aspart	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Aspart	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Aspart	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Aspart	The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs	Week 0 and Week 8
Weight Z Score	Z score of weight. To estimate the growth of children, standardised mean weight values were calculated for each month of age and for each sex	Week 0 and Week 8
Body Mass Index (BMI) Z Score	Z score of BMI index. To estimate the growth of children, standardised mean BMI values were calculated for each month of age and for each sex	Week 0 and Week 8
Incidence of Hypoglycaemic Episodes - All Episodes	Number of hypoglycaemic episodes from Week 0 to Week 8, defined as self-measurement plasma glucose less than 56 mg/dL (3.1 mmol/L). Classified as major, minor or symptoms only. Major if unable to treat her/himself (given the age of the study population, the definition of major hypoglycemia was to be adapted through the investigator's judgment). Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L (56 mg/dL). Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.	Weeks 0-8
Incidence of Hypoglycaemic Episodes - Glycaemia Below 0.56 g/L	Number of minor hypoglycaemic episodes from Week 0 to Week 8, defined as self-measurement plasma glucose below 3.1 mmol/L (56 mg/dL) and the child is able to treat her/himself.	Weeks 0-8
Incidence of Hypoglycaemic Episodes - Glycaemia Above or Equal to 0.56 g/L	Number of "symptoms only" hypoglycaemic episodes from Week 0 to Week 8, defined as self-measurement plasma glucose higher than or equal to 3.1 mmol/L (56 mg/dL) or no plasma glucose measurement and the child is able to treat her/himself.	Weeks 0-8
Percentage of Children Assessing Insulin Therapy Injection Pain as "Sad Face"	Via a paper diary, the children perceived insulin therapy injection pain by using a four-grade facial visual analogue scale (VAS): very sad face, sad face, happy face or very happy face.	Week 0 and Week 8
Percentage of Children Assessing Insulin Therapy Injection Pain as "Happy Face"	Via a paper diary, the children perceived insulin therapy injection pain by using a four-grade facial visual analogue scale (VAS): very sad face, sad face, happy face or very happy face.	Week 0 and week 8
Percentage of Children Assessing Insulin Therapy Injection Pain as "Very Happy Face"	Via a paper diary, the children perceived insulin therapy injection pain by using a four-grade facial visual analogue scale (VAS): very sad face, sad face, happy face or very happy face.	Week 0 and Week 8

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: October 10, 2007
• First Submitted That Met QC Criteria: October 10, 2007
• First Posted (Estimate): October 11, 2007

Study Record Updates

• Last Update Posted (Estimate): November 2, 2014
• Last Update Submitted That Met QC Criteria: October 24, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• 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 Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin Detemir
• Other Study ID Numbers: NN304-1813; 2006-006715-77 (EudraCT Number)