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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00542620
First received: October 10, 2007
Last updated: December 11, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Diabetes
Diabetes Mellitus, Type 1
Drug: insulin detemir
Drug: insulin aspart
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:
  • Glycosylated Haemoglobin A1c (HbA1c) [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    Measured for the Per Protocol (PP) set

  • Glycosylated Haemoglobin A1c (HbA1c) [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    Measured for the ITT (Intention-to-Treat) set


Secondary Outcome Measures:
  • Fructosamine [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
  • Self-measured Plasma Glucose Profile (Before Breakfast) [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
  • Self-measured Plasma Glucose Profile (After Breakfast) [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
  • Self-measured Plasma Glucose Profile (Before Dinner) [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
  • Self-measured Plasma Glucose Profile (After Dinner) [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Cmax of Free Insulin [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 0-8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 0-8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 0-8 ] [ Designated as safety issue: No ]
    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" [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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" [ Time Frame: Week 0 and week 8 ] [ Designated as safety issue: No ]
    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" [ Time Frame: Week 0 and Week 8 ] [ Designated as safety issue: No ]
    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.


Enrollment: 25
Study Start Date: September 2007
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Active Comparator: Separate injection 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

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00542620

Locations
France
Paris, France
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Bertrand Alexandre Novo Nordisk Pharmaceutique S.A.S.
  More Information

Additional Information:
No publications provided

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00542620     History of Changes
Other Study ID Numbers: NN304-1813, 2006-006715-77
Study First Received: October 10, 2007
Results First Received: December 5, 2011
Last Updated: December 11, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin
Insulin Aspart
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014