Clinical Trial Results:
A Trial comparing the Pharmacokinetic Properties of Fast-acting Insulin Aspart between Children, Adolescents and Adults with Type 1 Diabetes
Summary
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EudraCT number |
2017-002014-31 |
Trial protocol |
DE |
Global end of trial date |
05 Jul 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Jan 2019
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First version publication date |
05 Jan 2019
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NN1218-4371
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03407599 | ||
WHO universal trial number (UTN) |
U1111-1197-0428 | ||
Sponsors
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Sponsor organisation name |
Novo Nordisk A/S
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Sponsor organisation address |
Novo Allé, Bagsvaerd, Denmark, 2880
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Public contact |
Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Scientific contact |
Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Dec 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Jul 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Jul 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the total exposure of faster aspart between children, adolescents and adult
subjects with type 1 diabetes.
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Protection of trial subjects |
The trial was conducted in accordance with the Declaration of Helsinki and International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Good Clinical Practice, including archiving of essential documents and 21 Code of Federal Regulations (CFR) 312.120.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
08 Jan 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 43
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Worldwide total number of subjects |
43
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EEA total number of subjects |
43
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
12
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Adolescents (12-17 years) |
16
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Adults (18-64 years) |
15
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The trial was conducted at one site in Germany. | ||||||
Pre-assignment
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Screening details |
Not applicable | ||||||
Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Data analyst, Assessor | ||||||
Blinding implementation details |
Three sets of black sealed codes/labels containing information about the treatment were prepared for each subject. The sets were kept by the trial site (throughout the entire trial period), the local Novo Nordisk affiliate and the Novo Nordisk Global Safety department.
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Arms
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Arm title
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Total population | ||||||
Arm description |
Each subject was randomly allocated to a treatment sequence (faster aspart followed by NovoRapid® or NovoRapid® followed by faster aspart) consisting of 2 treatment periods. The two treatment periods (between first dosing visit and second dosing visit) were separated by a wash-out period of 3-22 days. | ||||||
Arm type |
Cross-over (experimental & active comparator) | ||||||
Investigational medicinal product name |
Faster aspart
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Investigational medicinal product code |
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Other name |
Fiasp®
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects were administered with a single dose of faster aspart 0.2 U/kg body weight just prior to a standard meal. Faster aspart was administered subcutaneously (s.c.) into a lifted skin fold of the lower abdominal wall above the inguinal area (lower lateral parts of the abdomen).
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Investigational medicinal product name |
Insulin aspart
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Investigational medicinal product code |
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Other name |
NovoRapid®
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects were administered with a single dose of NovoRapid® 0.2 U/kg body weight just prior to a standard meal. NovoRapid® was administered s.c. into a lifted skin fold of the lower abdominal wall above the inguinal area (lower lateral parts of the abdomen).
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Baseline characteristics reporting groups
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Reporting group title |
Total population
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Reporting group description |
Each subject was randomly allocated to a treatment sequence (faster aspart followed by NovoRapid® or NovoRapid® followed by faster aspart) consisting of 2 treatment periods. The two treatment periods (between first dosing visit and second dosing visit) were separated by a wash-out period of 3-22 days. | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Total population
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Reporting group description |
Each subject was randomly allocated to a treatment sequence (faster aspart followed by NovoRapid® or NovoRapid® followed by faster aspart) consisting of 2 treatment periods. The two treatment periods (between first dosing visit and second dosing visit) were separated by a wash-out period of 3-22 days. | ||
Subject analysis set title |
Faster aspart - Children
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Children subjects (6–11 years) received single dose of faster aspart in a cross-over manner in both treatment periods 1 and 2.
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Subject analysis set title |
Faster aspart - Adolescents
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Adolescent subjects (12–17 years) received single dose of faster aspart in a cross-over manner in both treatment periods 1 and 2.
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Subject analysis set title |
Faster aspart - Adults
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Adult subjects (18–64 years) received single dose of faster aspart in a cross-over manner in both treatment periods 1 and 2.
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Subject analysis set title |
NovoRapid® - Children
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Children subjects (6–11 years) received single dose of NovoRapid® in a cross-over manner in both treatment periods 1 and 2.
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Subject analysis set title |
NovoRapid® - Adolescents
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Adolescent subjects (12–17 years) received single dose of NovoRapid® in a cross-over manner in both treatment periods 1 and 2.
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Subject analysis set title |
NovoRapid® - Adults
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Adult subjects (18–64 years) received single dose of NovoRapid® in a cross-over manner in both treatment periods 1 and 2.
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End point title |
AUCIAsp,0–12h, area under the serum insulin aspart concentration-time curve | ||||||||||||||||||||||||||||
End point description |
This endpoint represents data for the free insulin aspart concentration for AUCIAsp,0–12h. Results are based on the full analysis set (FAS), which included all randomised subjects receiving at least one dose of one of the two investigational medicinal products (IMPs; faster aspart or NovoRapid®). Number of subjects analyzed = subjects with available data.
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End point type |
Primary
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End point timeframe |
From 0 to 12 hours
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Statistical analysis title |
Children: Faster aspart versus NovoRapid® | ||||||||||||||||||||||||||||
Statistical analysis description |
The endpoint was log-transformed and analysed using a linear mixed model with age group, treatment, period, and age group-by-treatment interaction as fixed effects, and subject as a random effect. Due to cross-over design of the study, the following “number of subjects included in analysis” is being erroneously displayed as 24. Actual “number of subjects included in analysis” is 12.
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Comparison groups |
NovoRapid® - Children v Faster aspart - Children
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Number of subjects included in analysis |
24
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||||||||||
Method |
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Parameter type |
Treatment ratio | ||||||||||||||||||||||||||||
Point estimate |
0.99
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.88 | ||||||||||||||||||||||||||||
upper limit |
1.11 | ||||||||||||||||||||||||||||
Statistical analysis title |
Adolescents: Faster aspart versus NovoRapid® | ||||||||||||||||||||||||||||
Statistical analysis description |
The endpoint was log-transformed and analysed using a linear mixed model with age group, treatment, period, and age group-by-treatment interaction as fixed effects, and subject as a random effect. Due to cross-over design of the study, the following “number of subjects included in analysis” is being erroneously displayed as 32. Actual “number of subjects included in analysis” is 16.
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Comparison groups |
Faster aspart - Adolescents v NovoRapid® - Adolescents
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Number of subjects included in analysis |
32
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||||||||||
Method |
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Parameter type |
Treatment ratio | ||||||||||||||||||||||||||||
Point estimate |
0.93
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.87 | ||||||||||||||||||||||||||||
upper limit |
1 | ||||||||||||||||||||||||||||
Statistical analysis title |
Adults: Faster aspart versus NovoRapid® | ||||||||||||||||||||||||||||
Statistical analysis description |
The endpoint was log-transformed and analysed using a linear mixed model with age group, treatment, period, and age group-by-treatment interaction as fixed effects, and subject as a random effect. Due to cross-over design of the study, the following “number of subjects included in analysis” is being erroneously displayed as 28. Actual “number of subjects included in analysis” is 15.
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Comparison groups |
Faster aspart - Adults v NovoRapid® - Adults
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Number of subjects included in analysis |
28
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||||||||||
Method |
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Parameter type |
Treatment ratio | ||||||||||||||||||||||||||||
Point estimate |
1
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.94 | ||||||||||||||||||||||||||||
upper limit |
1.07 | ||||||||||||||||||||||||||||
Statistical analysis title |
Faster aspart: Children versus adults | ||||||||||||||||||||||||||||
Statistical analysis description |
The endpoint was log-transformed and analysed using a linear mixed model with age group, treatment, period, and age group-by-treatment interaction as fixed effects, and subject as a random effect.
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Comparison groups |
Faster aspart - Children v Faster aspart - Adults
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Number of subjects included in analysis |
25
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||||||||||
Method |
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Parameter type |
Treatment ratio | ||||||||||||||||||||||||||||
Point estimate |
0.71
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.61 | ||||||||||||||||||||||||||||
upper limit |
0.83 | ||||||||||||||||||||||||||||
Statistical analysis title |
Faster aspart: Adolescents versus adults | ||||||||||||||||||||||||||||
Statistical analysis description |
The endpoint was log-transformed and analysed using a linear mixed model with age group, treatment, period, and age group-by-treatment interaction as fixed effects, and subject as a random effect.
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Comparison groups |
Faster aspart - Adolescents v Faster aspart - Adults
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Number of subjects included in analysis |
29
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||||||||||
Method |
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Parameter type |
Treatment ratio | ||||||||||||||||||||||||||||
Point estimate |
0.87
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.78 | ||||||||||||||||||||||||||||
upper limit |
0.98 | ||||||||||||||||||||||||||||
Statistical analysis title |
NovoRapid®: Children versus adults | ||||||||||||||||||||||||||||
Statistical analysis description |
The endpoint was log-transformed and analysed using a linear mixed model with age group, treatment, period, and age group-by-treatment interaction as fixed effects, and subject as a random effect.
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Comparison groups |
NovoRapid® - Children v NovoRapid® - Adults
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Number of subjects included in analysis |
27
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||||||||||
Method |
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Parameter type |
Treatment ratio | ||||||||||||||||||||||||||||
Point estimate |
0.72
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.62 | ||||||||||||||||||||||||||||
upper limit |
0.84 | ||||||||||||||||||||||||||||
Statistical analysis title |
NovoRapid®: Adolescents versus adults | ||||||||||||||||||||||||||||
Statistical analysis description |
The endpoint was log-transformed and analysed using a linear mixed model with age group, treatment, period, and age group-by-treatment interaction as fixed effects, and subject as a random effect.
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Comparison groups |
NovoRapid® - Adolescents v NovoRapid® - Adults
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||||||||||
Method |
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Parameter type |
Treatment ratio | ||||||||||||||||||||||||||||
Point estimate |
0.94
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.84 | ||||||||||||||||||||||||||||
upper limit |
1.05 |
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End point title |
Cmax,IAsp, maximum observed serum insulin aspart concentration | ||||||||||||||||||||||||||||
End point description |
This endpoint represents data for the free insulin aspart concentration for Cmax,IAsp. Results are based on the FAS. Number of subjects analyzed = subjects with available data.
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End point type |
Secondary
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End point timeframe |
Not applicable
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Day 1 to day 7 in both the treatment periods. Results are based on the safety analysis set, which included all subjects receiving at least one dose of one of the two IMPs.
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Adverse event reporting additional description |
An AE was defined as treatment emergent if, for each treatment period, the onset of the AE was in the period from time of first trial product administration to 7 days (7 times 24 hours) after trial product administration.
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Assessment type |
Systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
21.0
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Frequency threshold for reporting non-serious adverse events: 5% | |||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No non-serious adverse events with a prevalence of 5% are available for this trial. Number of subjects in individual treatment group with at least one non-serious adverse event areas follows: 3 subjects in faster aspart - children, 4 subjects in faster aspart- adolescents, 1 subject in faster aspart – adults, 2 subjects in NovoRapid® -children,1 subject in NovoRapid® - adolescents, and 1 subject in NovoRapid® - Adults. |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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02 Mar 2018 |
The date, time, and dose of the last trial product administration were modified to cover the last insulin administration prior to the hypoglycaemic episode. The amendment allowed the reporting of blood glucose (BG) values via subjects’ own BG meters in case they experienced a hypoglycaemic episode outside the clinical site. It was specified that an un-blinded monitor will receive a copy of the randomisation list in order to check that the trial products have been administered in accordance with the planned randomisation. The protocol was updated to specify that the destruction of the trial product will be performed upon completion of the trial after finalization of the drug accountability. It was specified that in case the target plasma glucose level cannot be established before 10:00 hours, the subject can be rescheduled once as per standard procedure. Administration of the meal by intravenous infusion was also allowed in addition to the subcutaneous route. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |