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

Diabetes Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00542620
• Other study ID #: NN304-1813
• Secondary ID: 2006-006715-77
• Status: Completed
• Phase: Phase 4
• First received: October 10, 2007
• Last updated: October 24, 2014
• Start date: September 2007
• Est. completion date: March 2009

Study information

• Verified date: October 2014
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 18 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Drug:
• insulin detemir
Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, mixed with insulin aspart
• insulin aspart
Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, mixed with insulin detemir
• insulin detemir
Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, injected separately with insulin aspart
• insulin aspart
Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, injected separately with insulin detemir

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycosylated Haemoglobin A1c (HbA1c)	Measured for the Per Protocol (PP) set	Week 0 and Week 8	No
Primary	Glycosylated Haemoglobin A1c (HbA1c)	Measured for the ITT (Intention-to-Treat) set	Week 0 and Week 8	No
Secondary	Fructosamine		Week 0 and Week 8	No
Secondary	Self-measured Plasma Glucose Profile (Before Breakfast)		Week 0 and Week 8	No
Secondary	Self-measured Plasma Glucose Profile (After Breakfast)		Week 0 and Week 8	No
Secondary	Self-measured Plasma Glucose Profile (Before Dinner)		Week 0 and Week 8	No
Secondary	Self-measured Plasma Glucose Profile (After Dinner)		Week 0 and Week 8	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

•   Clinical Trials at Novo Nordisk