Diabetes, Diabetes Mellitus, Type 1
Conditions
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.
Interventions
DRUGinsulin detemir
Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, mixed with insulin aspart
DRUGinsulin aspart
Treat-to-target (individually adjusted) dose titration, s.c. (under the skin) injection, twice a day, mixed with insulin detemir
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycosylated Haemoglobin A1c (HbA1c) | Week 0 and Week 8 | Measured for the Per Protocol (PP) set |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs |
| Fructosamine | Week 0 and Week 8 | — |
| Pharmacokinetics: Cmax of Insulin Aspart | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Week 0 and Week 8 | 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 | Weeks 0-8 | 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 | Weeks 0-8 | 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 | Weeks 0-8 | 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 | Week 0 and Week 8 | 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 | Week 0 and week 8 | 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 | Week 0 and Week 8 | 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. |
| Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Detemir | Week 0 and Week 8 | The observed peak drug concentration at time (T): T0, T0.5hour (hr), T1hr, T1.5hr, T2hrs, T2.5hrs, T3hrs, T3.5hrs, T4hrs |
Countries
France
Participant flow
Recruitment details
Four centres in France
Pre-assignment details
Children with type 1 diabetes currently treated with insulin detemir and insulin aspart and with a good glycaemic control. At trial entry, subjects must be 6-18 years old with a HbA1c (glycosylated haemoglobin) below or equal to 8.6%
Participants by arm
| Arm | Count |
|---|---|
| Mixed Injection Individually adjusted insulin detemir extemporaneous mixed with individually adjusted insulin aspart injected s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed | 13 |
| Separate Injection Individually adjusted insulin detemir and individually adjusted insulin aspart injected separately s.c. twice daily (in the morning and in the evening) + extra insulin aspart at lunch and breaks, if needed | 12 |
| Total | 25 |
Baseline characteristics
| Characteristic | Mixed Injection | Separate Injection | Total |
|---|---|---|---|
| Age, Continuous | 11.6 years STANDARD_DEVIATION 2.6 | 10.9 years STANDARD_DEVIATION 2.5 | 11.3 years STANDARD_DEVIATION 2.5 |
| Diabetes history | 6.68 years STANDARD_DEVIATION 3.51 | 6.13 years STANDARD_DEVIATION 2.38 | 6.42 years STANDARD_DEVIATION 2.97 |
| Region of Enrollment France | 13 participants | 12 participants | 25 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 12 | 9 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 |
Outcome results
Primary
Glycosylated Haemoglobin A1c (HbA1c)
Measured for the Per Protocol (PP) set
Time frame: Week 0 and Week 8
Population: Per Protocol (PP) analysis set consists of all the ITT (Intention-to-Treat) subjects who did not present any significant protocol deviations that could potentially affect the efficacy results. One subject was excluded from PP as subject received separate injections despite being randomised to receive mixed injections.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Glycosylated Haemoglobin A1c (HbA1c) | Week 0 | 8.00 percentage of total haemoglobin | Standard Deviation 0.54 |
| Mixed Injection | Glycosylated Haemoglobin A1c (HbA1c) | Week 8 | 7.63 percentage of total haemoglobin | Standard Deviation 0.55 |
| Separate Injection | Glycosylated Haemoglobin A1c (HbA1c) | Week 0 | 7.77 percentage of total haemoglobin | Standard Deviation 0.55 |
| Separate Injection | Glycosylated Haemoglobin A1c (HbA1c) | Week 8 | 8.15 percentage of total haemoglobin | Standard Deviation 0.57 |
p-value: 0.00195% CI: [-1.049, -0.334]ANCOVA
Primary
Glycosylated Haemoglobin A1c (HbA1c)
Measured for the ITT (Intention-to-Treat) set
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Glycosylated Haemoglobin A1c (HbA1c) | Week 0 | 7.93 percentage of total haemoglobin | Standard Deviation 0.57 |
| Mixed Injection | Glycosylated Haemoglobin A1c (HbA1c) | Week 8 | 7.65 percentage of total haemoglobin | Standard Deviation 0.53 |
| Separate Injection | Glycosylated Haemoglobin A1c (HbA1c) | Week 0 | 7.77 percentage of total haemoglobin | Standard Deviation 0.55 |
| Separate Injection | Glycosylated Haemoglobin A1c (HbA1c) | Week 8 | 8.15 percentage of total haemoglobin | Standard Deviation 0.57 |
p-value: 0.00395% CI: [-0.97, -0.219]ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Body Mass Index (BMI) Z Score | Week 0, n=13, 12 | -0.32 Z-score | Standard Deviation 0.63 |
| Mixed Injection | Body Mass Index (BMI) Z Score | Week 8, n=11, 12 | -0.07 Z-score | Standard Deviation 0.52 |
| Separate Injection | Body Mass Index (BMI) Z Score | Week 0, n=13, 12 | 0.04 Z-score | Standard Deviation 0.86 |
| Separate Injection | Body Mass Index (BMI) Z Score | Week 8, n=11, 12 | 0.26 Z-score | Standard Deviation 0.73 |
p-value: 0.665ANCOVA
Secondary
Fructosamine
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Fructosamine | Week 0, n=13, 12 | 334.8 mmol/L | Standard Deviation 35.9 |
| Mixed Injection | Fructosamine | Week 8, n=12, 12 | 316.4 mmol/L | Standard Deviation 30.1 |
| Separate Injection | Fructosamine | Week 0, n=13, 12 | 319.8 mmol/L | Standard Deviation 22.6 |
| Separate Injection | Fructosamine | Week 8, n=12, 12 | 334.8 mmol/L | Standard Deviation 41.9 |
p-value: 0.57395% CI: [-38.77, 22.08]ANCOVA
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.
Time frame: Weeks 0-8
Population: All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subjects are analysed based on treatments actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mixed Injection | Incidence of Hypoglycaemic Episodes - All Episodes | 351 episodes |
| Separate Injection | Incidence of Hypoglycaemic Episodes - All Episodes | 293 episodes |
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.
Time frame: Weeks 0-8
Population: All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subjects are analysed based on treatments actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mixed Injection | Incidence of Hypoglycaemic Episodes - Glycaemia Above or Equal to 0.56 g/L | With symptoms | 49 episodes |
| Mixed Injection | Incidence of Hypoglycaemic Episodes - Glycaemia Above or Equal to 0.56 g/L | Without (w/o) symptoms | 131 episodes |
| Mixed Injection | Incidence of Hypoglycaemic Episodes - Glycaemia Above or Equal to 0.56 g/L | W/o information on presence of symptoms | 5 episodes |
| Separate Injection | Incidence of Hypoglycaemic Episodes - Glycaemia Above or Equal to 0.56 g/L | With symptoms | 46 episodes |
| Separate Injection | Incidence of Hypoglycaemic Episodes - Glycaemia Above or Equal to 0.56 g/L | Without (w/o) symptoms | 33 episodes |
| Separate Injection | Incidence of Hypoglycaemic Episodes - Glycaemia Above or Equal to 0.56 g/L | W/o information on presence of symptoms | 1 episodes |
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.
Time frame: Weeks 0-8
Population: All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subjects are analysed based on treatments actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mixed Injection | Incidence of Hypoglycaemic Episodes - Glycaemia Below 0.56 g/L | With symptoms | 68 episodes |
| Mixed Injection | Incidence of Hypoglycaemic Episodes - Glycaemia Below 0.56 g/L | Without (w/o) symptoms | 75 episodes |
| Mixed Injection | Incidence of Hypoglycaemic Episodes - Glycaemia Below 0.56 g/L | W/o info on presence of symptoms | 23 episodes |
| Separate Injection | Incidence of Hypoglycaemic Episodes - Glycaemia Below 0.56 g/L | With symptoms | 159 episodes |
| Separate Injection | Incidence of Hypoglycaemic Episodes - Glycaemia Below 0.56 g/L | Without (w/o) symptoms | 48 episodes |
| Separate Injection | Incidence of Hypoglycaemic Episodes - Glycaemia Below 0.56 g/L | W/o info on presence of symptoms | 6 episodes |
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.
Time frame: Week 0 and week 8
Population: All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subjects are analysed based on treatments actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mixed Injection | Percentage of Children Assessing Insulin Therapy Injection Pain as Happy Face | Week 0 | 27 percentage of subjects |
| Mixed Injection | Percentage of Children Assessing Insulin Therapy Injection Pain as Happy Face | Week 8 | 81 percentage of subjects |
| Separate Injection | Percentage of Children Assessing Insulin Therapy Injection Pain as Happy Face | Week 0 | 50 percentage of subjects |
| Separate Injection | Percentage of Children Assessing Insulin Therapy Injection Pain as Happy Face | Week 8 | 69 percentage of subjects |
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.
Time frame: Week 0 and Week 8
Population: All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subjects are analysed based on treatments actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mixed Injection | Percentage of Children Assessing Insulin Therapy Injection Pain as Sad Face | Week 0 | 45 percentage of subjects |
| Mixed Injection | Percentage of Children Assessing Insulin Therapy Injection Pain as Sad Face | Week 8 | 0 percentage of subjects |
| Separate Injection | Percentage of Children Assessing Insulin Therapy Injection Pain as Sad Face | Week 0 | 33 percentage of subjects |
| Separate Injection | Percentage of Children Assessing Insulin Therapy Injection Pain as Sad Face | Week 8 | 23 percentage of subjects |
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.
Time frame: Week 0 and Week 8
Population: All randomised subjects who received at least one treatment dose are taken into account in the safety analysis set. Subjects are analysed based on treatments actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mixed Injection | Percentage of Children Assessing Insulin Therapy Injection Pain as Very Happy Face | Week 0 | 27.3 percentage of subjects |
| Mixed Injection | Percentage of Children Assessing Insulin Therapy Injection Pain as Very Happy Face | Week 8 | 18.2 percentage of subjects |
| Separate Injection | Percentage of Children Assessing Insulin Therapy Injection Pain as Very Happy Face | Week 0 | 16.7 percentage of subjects |
| Separate Injection | Percentage of Children Assessing Insulin Therapy Injection Pain as Very Happy Face | Week 8 | 7.7 percentage of subjects |
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation. CGMS® data not available/sufficient for pre-study evaluation in five subjects or at post-study evaluation in four subjects.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Free Insulin | Week 0, n=8, 9 | 1441.3 pmol.h/L | Standard Deviation 7516.22 |
| Mixed Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Free Insulin | Week 8, n=11, 11 | 1981.1 pmol.h/L | Standard Deviation 1442.49 |
| Separate Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Free Insulin | Week 0, n=8, 9 | 752.1 pmol.h/L | Standard Deviation 4128.04 |
| Separate Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Free Insulin | Week 8, n=11, 11 | 672.8 pmol.h/L | Standard Deviation 7156.05 |
p-value: 0.534ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Aspart | Week 0, n=10, 11 | 3008.1 pmol.h/L | Standard Deviation 7689.04 |
| Mixed Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Aspart | Week 8, n=13, 12 | 5674.3 pmol.h/L | Standard Deviation 10668.8 |
| Separate Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Aspart | Week 0, n=10, 11 | 3006.3 pmol.h/L | Standard Deviation 4458.12 |
| Separate Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Aspart | Week 8, n=13, 12 | 3019.9 pmol.h/L | Standard Deviation 1013.19 |
p-value: 0.023ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation. CGMS® data not available/sufficient for pre-study evaluation in five subjects or at post-study evaluation in four subjects
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Detemir | Week 0, n=4, 3 | 230728.2 pmol.h/L | Standard Deviation 304790.62 |
| Mixed Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Detemir | Week 8, n=3, 6 | 123555.7 pmol.h/L | Standard Deviation 141207.72 |
| Separate Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Detemir | Week 0, n=4, 3 | 68509.6 pmol.h/L | Standard Deviation 116350.34 |
| Separate Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to Infinity of Insulin Detemir | Week 8, n=3, 6 | 362313.5 pmol.h/L | Standard Deviation 4287360.41 |
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Free Insulin | Week 0 | 638.4 pmol.h/L | Standard Deviation 1022.95 |
| Mixed Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Free Insulin | Week 8 | 819.6 pmol.h/L | Standard Deviation 310.41 |
| Separate Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Free Insulin | Week 0 | 398.9 pmol.h/L | Standard Deviation 395.19 |
| Separate Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Free Insulin | Week 8 | 466.2 pmol.h/L | Standard Deviation 266.93 |
p-value: 0.234ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Aspart | Week 0 | 1546.3 pmol.h/L | Standard Deviation 3163.27 |
| Mixed Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Aspart | Week 8 | 2102.4 pmol.h/L | Standard Deviation 1378.73 |
| Separate Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Aspart | Week 0 | 1510.9 pmol.h/L | Standard Deviation 963.37 |
| Separate Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Aspart | Week 8 | 1540 pmol.h/L | Standard Deviation 894.4 |
p-value: 0.166ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Detemir | Week 0 | 36591.2 pmol.h/L | Standard Deviation 70709.5 |
| Mixed Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Detemir | Week 8 | 36055.0 pmol.h/L | Standard Deviation 73609.6 |
| Separate Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Detemir | Week 0 | 34653.4 pmol.h/L | Standard Deviation 21243.3 |
| Separate Injection | Pharmacokinetics: Area Under the Concentration vs. Time Curve From Time Zero to the Time of the Last Measured Level of Insulin Detemir | Week 8 | 39757.0 pmol.h/L | Standard Deviation 23076.5 |
p-value: 0.471ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Cmax of Free Insulin | Week 0 | 216 pmol/L | Standard Deviation 542.4 |
| Mixed Injection | Pharmacokinetics: Cmax of Free Insulin | Week 8 | 274 pmol/L | Standard Deviation 109.2 |
| Separate Injection | Pharmacokinetics: Cmax of Free Insulin | Week 0 | 167 pmol/L | Standard Deviation 130.4 |
| Separate Injection | Pharmacokinetics: Cmax of Free Insulin | Week 8 | 186 pmol/L | Standard Deviation 105.5 |
p-value: 0.209ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Cmax of Insulin Aspart | Week 0 | 557 pmol/L | Standard Deviation 2784.2 |
| Mixed Injection | Pharmacokinetics: Cmax of Insulin Aspart | Week 8 | 662 pmol/L | Standard Deviation 576.3 |
| Separate Injection | Pharmacokinetics: Cmax of Insulin Aspart | Week 0 | 762 pmol/L | Standard Deviation 378.3 |
| Separate Injection | Pharmacokinetics: Cmax of Insulin Aspart | Week 8 | 601 pmol/L | Standard Deviation 355.3 |
p-value: 0.127ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Cmax of Insulin Detemir | Week 0 | 10700 pmol/L | Standard Deviation 25149.9 |
| Mixed Injection | Pharmacokinetics: Cmax of Insulin Detemir | Week 8 | 12000 pmol/L | Standard Deviation 23807.2 |
| Separate Injection | Pharmacokinetics: Cmax of Insulin Detemir | Week 0 | 10500 pmol/L | Standard Deviation 6840.2 |
| Separate Injection | Pharmacokinetics: Cmax of Insulin Detemir | Week 8 | 12600 pmol/L | Standard Deviation 8426.6 |
p-value: 0.727ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation. CGMS® data not available/sufficient for pre-study evaluation in five subjects or at post-study evaluation in four subjects
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Free Insulin | Week 0, n=8, 9 | 3.6 hours | Standard Deviation 17.84 |
| Mixed Injection | Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Free Insulin | Week 8, n=11, 11 | 2.9 hours | Standard Deviation 3.34 |
| Separate Injection | Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Free Insulin | Week 0, n=8, 9 | 2.3 hours | Standard Deviation 10.93 |
| Separate Injection | Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Free Insulin | Week 8, n=11, 11 | 2.0 hours | Standard Deviation 11.62 |
p-value: 0.722ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Aspart | Week 0, n=10, 11 | 2.2 hours | Standard Deviation 6.75 |
| Mixed Injection | Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Aspart | Week 8, n=13, 12 | 3.5 hours | Standard Deviation 41.88 |
| Separate Injection | Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Aspart | Week 0, n=10, 11 | 2 hours | Standard Deviation 3.09 |
| Separate Injection | Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Aspart | Week 8, n=13, 12 | 1.7 hours | Standard Deviation 1.62 |
p-value: 0.439ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. CGMS® data not available/sufficient for pre-study evaluation in five subjects or at post-study evaluation in four subjects
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Detemir | Week 0, n=4, 3 | 16.2 hours | Standard Deviation 4.12 |
| Mixed Injection | Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Detemir | Week 8, n=3, 6 | 5.6 hours | Standard Deviation 4.2 |
| Separate Injection | Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Detemir | Week 0, n=4, 3 | 8.2 hours | Standard Deviation 6.53 |
| Separate Injection | Pharmacokinetics: Terminal Phase Elimination Half-life (T½) - Parameter of Insulin Detemir | Week 8, n=3, 6 | 20.8 hours | Standard Deviation 249.57 |
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Tmax of Free Insulin | Week 0 | 2.5 hours | Standard Deviation 0.74 |
| Mixed Injection | Pharmacokinetics: Tmax of Free Insulin | Week 8 | 2.5 hours | Standard Deviation 0.8 |
| Separate Injection | Pharmacokinetics: Tmax of Free Insulin | Week 0 | 3.0 hours | Standard Deviation 0.98 |
| Separate Injection | Pharmacokinetics: Tmax of Free Insulin | Week 8 | 1.8 hours | Standard Deviation 0.72 |
p-value: 0.22ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Tmax of Insulin Aspart | Week 8 | 2 hours | Standard Deviation 0.53 |
| Mixed Injection | Pharmacokinetics: Tmax of Insulin Aspart | Week 0 | 2 hours | Standard Deviation 0.99 |
| Separate Injection | Pharmacokinetics: Tmax of Insulin Aspart | Week 0 | 2 hours | Standard Deviation 0.97 |
| Separate Injection | Pharmacokinetics: Tmax of Insulin Aspart | Week 8 | 1.5 hours | Standard Deviation 0.51 |
p-value: 0.1ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Pharmacokinetics: Tmax of Insulin Detemir | Week 0 | 3.5 hours | Standard Deviation 0.93 |
| Mixed Injection | Pharmacokinetics: Tmax of Insulin Detemir | Week 8 | 3.5 hours | Standard Deviation 0.38 |
| Separate Injection | Pharmacokinetics: Tmax of Insulin Detemir | Week 0 | 3.5 hours | Standard Deviation 0.48 |
| Separate Injection | Pharmacokinetics: Tmax of Insulin Detemir | Week 8 | 3.3 hours | Standard Deviation 0.78 |
p-value: 0.411ANCOVA
Secondary
Self-measured Plasma Glucose Profile (After Breakfast)
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Self-measured Plasma Glucose Profile (After Breakfast) | Week 0, n=5, 6 | 123.00 mg/dL | Standard Deviation 61.9 |
| Mixed Injection | Self-measured Plasma Glucose Profile (After Breakfast) | Week 8, n=4, 7 | 208.08 mg/dL | Standard Deviation 48.19 |
| Separate Injection | Self-measured Plasma Glucose Profile (After Breakfast) | Week 0, n=5, 6 | 164.89 mg/dL | Standard Deviation 73.33 |
| Separate Injection | Self-measured Plasma Glucose Profile (After Breakfast) | Week 8, n=4, 7 | 167.98 mg/dL | Standard Deviation 70.64 |
p-value: 0.389ANCOVA
Secondary
Self-measured Plasma Glucose Profile (After Dinner)
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation. CGMS® data not available/sufficient for pre-study evaluation in five subjects or at post-study evaluation in four subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Self-measured Plasma Glucose Profile (After Dinner) | Week 0, n=8, 5 | 175.38 mg/dL | Standard Deviation 58.47 |
| Mixed Injection | Self-measured Plasma Glucose Profile (After Dinner) | Week 8, n=7, 6 | 198.00 mg/dL | Standard Deviation 53.85 |
| Separate Injection | Self-measured Plasma Glucose Profile (After Dinner) | Week 0, n=8, 5 | 201.80 mg/dL | Standard Deviation 59.12 |
| Separate Injection | Self-measured Plasma Glucose Profile (After Dinner) | Week 8, n=7, 6 | 187.67 mg/dL | Standard Deviation 85.63 |
p-value: 0.917ANCOVA
Secondary
Self-measured Plasma Glucose Profile (Before Breakfast)
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Self-measured Plasma Glucose Profile (Before Breakfast) | Week 0 | 190.31 mg/dL | Standard Deviation 56.8 |
| Mixed Injection | Self-measured Plasma Glucose Profile (Before Breakfast) | Week 8 | 162.96 mg/dL | Standard Deviation 57.46 |
| Separate Injection | Self-measured Plasma Glucose Profile (Before Breakfast) | Week 0 | 165.39 mg/dL | Standard Deviation 70.28 |
| Separate Injection | Self-measured Plasma Glucose Profile (Before Breakfast) | Week 8 | 204.75 mg/dL | Standard Deviation 59.25 |
p-value: 0.063ANCOVA
Secondary
Self-measured Plasma Glucose Profile (Before Dinner)
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Self-measured Plasma Glucose Profile (Before Dinner) | Week 0 | 199.14 mg/dL | Standard Deviation 42.05 |
| Mixed Injection | Self-measured Plasma Glucose Profile (Before Dinner) | Week 8 | 185.23 mg/dL | Standard Deviation 66.3 |
| Separate Injection | Self-measured Plasma Glucose Profile (Before Dinner) | Week 0 | 201.44 mg/dL | Standard Deviation 57.5 |
| Separate Injection | Self-measured Plasma Glucose Profile (Before Dinner) | Week 8 | 181.03 mg/dL | Standard Deviation 68.41 |
p-value: 0.856ANCOVA
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
Time frame: Week 0 and Week 8
Population: Intention-to-treat (ITT) analysis set consists of all randomised children with a signed informed consent and at least one HbA1c value determined after randomisation. Subjects are analysed based on initial randomisation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mixed Injection | Weight Z Score | Week 0, n=13, 12 | -0.42 Z-score | Standard Deviation 0.71 |
| Mixed Injection | Weight Z Score | Week 8, n=11, 12 | -0.29 Z-score | Standard Deviation 0.65 |
| Separate Injection | Weight Z Score | Week 0, n=13, 12 | 0.19 Z-score | Standard Deviation 0.69 |
| Separate Injection | Weight Z Score | Week 8, n=11, 12 | 0.26 Z-score | Standard Deviation 0.67 |
p-value: 0.202ANCOVA