Back to resultsComparison of Insulin Detemir and Insulin Aspart in 2 Separate Injections Twice Daily to Extemporaneous Mixing Injection Regimen Twice Daily - The Paediatric Mixing Trial (MIXING)
Primary Purpose
Diabetes, Diabetes Mellitus, Type 1
Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
insulin detemir
insulin aspart
insulin detemir
insulin aspart
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Mixed injection
Separate injection
Arm Description
Outcomes
Primary Outcome Measures
Glycosylated Haemoglobin A1c (HbA1c)
Measured for the Per Protocol (PP) set
Glycosylated Haemoglobin A1c (HbA1c)
Measured for the ITT (Intention-to-Treat) set
Secondary Outcome Measures
Fructosamine
Self-measured Plasma Glucose Profile (Before Breakfast)
Self-measured Plasma Glucose Profile (After Breakfast)
Self-measured Plasma Glucose Profile (Before Dinner)
Self-measured Plasma Glucose Profile (After Dinner)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00542620
Brief Title
Comparison of Insulin Detemir and Insulin Aspart in 2 Separate Injections Twice Daily to Extemporaneous Mixing Injection Regimen Twice Daily - The Paediatric Mixing Trial
Acronym
MIXING
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
March 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes, Diabetes Mellitus, Type 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mixed injection
Arm Type
Experimental
Arm Title
Separate injection
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
insulin detemir
Intervention Description
Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, mixed with insulin aspart
Intervention Type
Drug
Intervention Name(s)
insulin aspart
Intervention Description
Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, mixed with insulin detemir
Intervention Type
Drug
Intervention Name(s)
insulin detemir
Intervention Description
Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, injected separately with insulin aspart
Intervention Type
Drug
Intervention Name(s)
insulin aspart
Intervention Description
Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, injected separately with insulin detemir
Primary Outcome Measure Information:
Title
Glycosylated Haemoglobin A1c (HbA1c)
Description
Measured for the Per Protocol (PP) set
Time Frame
Week 0 and Week 8
Title
Glycosylated Haemoglobin A1c (HbA1c)
Description
Measured for the ITT (Intention-to-Treat) set
Time Frame
Week 0 and Week 8
Secondary Outcome Measure Information:
Title
Fructosamine
Time Frame
Week 0 and Week 8
Title
Self-measured Plasma Glucose Profile (Before Breakfast)
Time Frame
Week 0 and Week 8
Title
Self-measured Plasma Glucose Profile (After Breakfast)
Time Frame
Week 0 and Week 8
Title
Self-measured Plasma Glucose Profile (Before Dinner)
Time Frame
Week 0 and Week 8
Title
Self-measured Plasma Glucose Profile (After Dinner)
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Cmax of Free Insulin
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2 hours (hrs), T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Tmax of Free Insulin
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Free Insulin
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Free Insulin
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Free Insulin
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Cmax of Insulin Detemir
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Tmax of Insulin Detemir
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Detemir
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Detemir
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Detemir
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Cmax of Insulin Aspart
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Tmax of Insulin Aspart
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Aspart
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Aspart
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Aspart
Description
The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs
Time Frame
Week 0 and Week 8
Title
Weight Z Score
Description
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
Time Frame
Week 0 and Week 8
Title
Body Mass Index (BMI) Z Score
Description
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
Time Frame
Week 0 and Week 8
Title
Incidence of Hypoglycaemic Episodes - All Episodes
Description
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.
Time Frame
Weeks 0-8
Title
Incidence of Hypoglycaemic Episodes - Glycaemia Below 0.56 g/L
Description
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.
Time Frame
Weeks 0-8
Title
Incidence of Hypoglycaemic Episodes - Glycaemia Above or Equal to 0.56 g/L
Description
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.
Time Frame
Weeks 0-8
Title
Percentage of Children Assessing Insulin Therapy Injection Pain as "Sad Face"
Description
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.
Time Frame
Week 0 and Week 8
Title
Percentage of Children Assessing Insulin Therapy Injection Pain as "Happy Face"
Description
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.
Time Frame
Week 0 and week 8
Title
Percentage of Children Assessing Insulin Therapy Injection Pain as "Very Happy Face"
Description
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.
Time Frame
Week 0 and Week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Registry (GCR, 1452)
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
Facility Information:
City
Paris
Country
France
12. IPD Sharing Statement
Links:
URL
http://novonordisk-trials.com
Description
Clinical Trials at Novo Nordisk
Learn more about this trial
Comparison of Insulin Detemir and Insulin Aspart in 2 Separate Injections Twice Daily to Extemporaneous Mixing Injection Regimen Twice Daily - The Paediatric Mixing Trial
We'll reach out to this number within 24 hrs