Clinical Trial Results:
Efficacy and Safety of Continuous Subcutaneous Insulin Infusion of Faster-acting Insulin Aspart compared to NovoRapid® in Adults with Type 1 Diabetes
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Summary
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EudraCT number |
2010-024054-11 |
Trial protocol |
NL DE BE FR SI GB |
Global end of trial date |
21 Jul 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Jul 2018
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First version publication date |
25 Jul 2018
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Other versions |
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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 |
NN1218-3854
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02825251 | ||
WHO universal trial number (UTN) |
U1111-1118-2480 | ||
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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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Feb 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Jun 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Jul 2017
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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 confirm the effect of CSII treatment with faster aspart in terms of glycaemic control by
comparing it to CSII treatment with NovoRapid®/NovoLog®, in adults with Type 1 Diabetes
Mellitus (T1DM), using a non-inferiority approach.
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Protection of trial subjects |
The trial was conducted in accordance with the Declaration of Helsinki Amended 2013 and ICH Good Clinical Practice (1996), including archiving of essential documents and 21 CFR 312.120.
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Background therapy |
Not applicable. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
06 Jul 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Belgium: 36
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Country: Number of subjects enrolled |
Canada: 45
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Country: Number of subjects enrolled |
France: 35
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Country: Number of subjects enrolled |
Germany: 63
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Country: Number of subjects enrolled |
Netherlands: 20
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Country: Number of subjects enrolled |
Russian Federation: 55
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Country: Number of subjects enrolled |
Slovenia: 33
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Country: Number of subjects enrolled |
United Kingdom: 27
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Country: Number of subjects enrolled |
United States: 158
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Worldwide total number of subjects |
472
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EEA total number of subjects |
214
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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) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
432
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From 65 to 84 years |
40
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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 92 sites in 9 countries as follows: Belgium (7), Canada (8), France (10), Germany (9), Netherlands (9), Russian Federation (11), Slovenia (2), United Kingdom (6), and United States (30). One (1) site in the Netherlands screened, but didn’t randomise any subject. | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
There was a 4-week run-in period primarily for reinforcement of subject training in trial procedures, diabetes education and collecting baseline assessments. Subjects remained on their pre-trial insulin treatment during the run-in period. | ||||||||||||||||||||||||
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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 | ||||||||||||||||||||||||
Blinding implementation details |
As the trial was blinded with regard to faster aspart and NovoRapid®, only dispensing unit numbers (DUNs) allocated by the interactive voice/web response system (IV/WRS) were dispensed to the subject. Trial products were packaged in non-subject specific boxes.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Faster aspart | ||||||||||||||||||||||||
Arm description |
The subjects received faster aspart (basal-bolus regimen) by continuous subcutaneous insulin infusion (CSII) for 16 weeks. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Insulin 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 |
Doses of basal and bolus insulin and timing of bolus dose were individually adjusted and thus no maximum dose of insulin was specified. Basal rate insulin adjustment: The purpose of adjusting the basal rates was to ensure that blood glucose (BG) was kept between 4.0–6.0 mmol/L [71–108 mg/dL] while in a fasting state and during the night. Bolus insulin titration: It was recommended that mealtime bolus insulin was titrated based on carbohydrate-counting using the Bolus Wizard® according to their usual practice and according to instructions from the investigator. Meal-time dosing was defined as bolus infusion initiated 0-2 minutes before a meal.
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Arm title
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NovoRapid | ||||||||||||||||||||||||
Arm description |
The subjects received insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) by CSII for 16 weeks. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Insulin aspart
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Investigational medicinal product code |
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Other name |
NovoRapid®, NovoLog®
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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 |
Doses of basal and bolus insulin and timing of bolus dose were individually adjusted and thus no maximum dose of insulin was specified. Basal rate insulin adjustment: The purpose of adjusting the basal rates was to ensure that BG was kept between 4.0–6.0 mmol/L [71–108 mg/dL] while in a fasting state and during the night. Bolus insulin titration: It was recommended that meal-time bolus insulin was titrated based on carbohydrate-counting using the Bolus Wizard® according to their usual practice and according to instructions from the investigator. Meal-time dosing was defined as bolus infusion initiated 0-2 minutes before a meal.
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Baseline characteristics reporting groups
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Reporting group title |
Faster aspart
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Reporting group description |
The subjects received faster aspart (basal-bolus regimen) by continuous subcutaneous insulin infusion (CSII) for 16 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NovoRapid
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Reporting group description |
The subjects received insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) by CSII for 16 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Faster aspart
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Reporting group description |
The subjects received faster aspart (basal-bolus regimen) by continuous subcutaneous insulin infusion (CSII) for 16 weeks. | ||
Reporting group title |
NovoRapid
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Reporting group description |
The subjects received insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) by CSII for 16 weeks. | ||
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End point title |
Change from baseline in glycosylated haemoglobin (HbA1c) | ||||||||||||||||||
End point description |
Change from baseline (week 0) in HbA1c was evaluated 16 weeks after randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In-trial period: the observation period from date of randomisation until last trial-related subject-site contact. Results are based on the FAS, which included all randomised subjects. Number of subjects analysed = Number of subjects contributed to the analysis.
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End point type |
Primary
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End point timeframe |
16 weeks after randomisation
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Statistical analysis title |
Faster aspart versus NovoRapid | ||||||||||||||||||
Statistical analysis description |
Change from baseline in HbA1c was analysed using an analysis of variance model after multiple imputation assuming treatment according to randomisation. The model included treatment, strata (use of own continuous glucose monitoring), previous insulin use, and region as factors, and baseline HbA1c as a covariate.
Non-inferiority of faster aspart was considered confirmed if the upper limit of the two-sided 95 % CI for the true treatment-difference D (faster aspart minus NovoRapid®) was below 0.4 %.
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Comparison groups |
Faster aspart v NovoRapid
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Number of subjects included in analysis |
472
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||
Method |
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Parameter type |
Treatment difference | ||||||||||||||||||
Point estimate |
0.09
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Confidence interval |
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95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
0.01 | ||||||||||||||||||
upper limit |
0.17 | ||||||||||||||||||
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End point title |
Change from baseline in 1-hour PPG increment (meal test) | ||||||||||||||||||
End point description |
Change from baseline (week 0) in 1-hour postprandial glucose (PPG) increment was evaluated 16 weeks after randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. Results are based on the FAS, which included all randomised subjects. Number of subjects analysed (N) = Number of subjects contributed to the analysis.
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End point type |
Secondary
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End point timeframe |
16 weeks after randomisation
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End point title |
Change from baseline in 1,5-anhydroglucitol | ||||||||||||||||||
End point description |
Change from baseline (week 0) in 1,5-anhydroglucitol was evaluated 16 weeks after randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. Results are based on the FAS, which included all randomised subjects. Number of subjects analysed (N) = Number of subjects contributed to the analysis.
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End point type |
Secondary
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End point timeframe |
16 weeks after randomisation
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change from baseline of time spent in low IG (≤3.9 mmol/L [70 mg/dL]) during CGM | ||||||||||||||||||
End point description |
Change from baseline (week 0) in low interstitial glucose (IG) (≤3.9 mmol/L [70 mg/dL]) during continuous glucose monitoring (CGM) was evaluated 16 weeks after randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. Results are based on the FAS, which included all randomised subjects. Number of subjects analysed (N) = Number of subjects contributed to the analysis.
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End point type |
Secondary
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End point timeframe |
16 weeks after randomisation
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Week 0 to Week 16 + 7 days. Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational medicinal product (IMP; faster aspart) or its comparator (NovoRapid®).
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20
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Reporting groups
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Reporting group title |
Faster aspart
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Reporting group description |
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Reporting group title |
NovoRapid
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/28918652 |
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