Clinical Trial Results:
Efficacy and Safety of Faster-acting Insulin Aspart compared to NovoRapid® both in Combination with Insulin Degludec in Children and Adolescents with Type 1 Diabetes
Summary
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EudraCT number |
2014-002568-33 |
Trial protocol |
BG CZ EE DE LV LT FI PL IT |
Global end of trial date |
03 Mar 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Sep 2018
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First version publication date |
19 Sep 2018
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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 |
NN1218-4101
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02670915 | ||
WHO universal trial number (UTN) |
U1111-1158-1170 | ||
Other trial identifiers |
Japanese trial registration: JapicCTI-163248 | ||
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 |
17 Aug 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Feb 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Mar 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 confirm the effect of treatment with meal-time faster-acting insulin aspart in terms of glycaemic control by comparing it to meal-time NovoRapid® both in combination with insulin degludec using a non-inferiority approach in children and adolescents with type 1 diabetes.
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Protection of trial subjects |
The trial was conducted in accordance with the Declaration of Helsinki and ICH Good Clinical Practice, including archiving of essential documents and FDA 21 CFR 312.120.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
04 May 2016
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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 |
Bulgaria: 48
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Country: Number of subjects enrolled |
Czech Republic: 36
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Country: Number of subjects enrolled |
Germany: 18
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Country: Number of subjects enrolled |
Estonia: 17
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Country: Number of subjects enrolled |
Finland: 13
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Country: Number of subjects enrolled |
India: 59
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Country: Number of subjects enrolled |
Israel: 31
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Country: Number of subjects enrolled |
Italy: 29
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Country: Number of subjects enrolled |
Japan: 66
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Country: Number of subjects enrolled |
Lithuania: 10
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Country: Number of subjects enrolled |
Latvia: 13
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Country: Number of subjects enrolled |
Poland: 22
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Country: Number of subjects enrolled |
Russian Federation: 104
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Country: Number of subjects enrolled |
Serbia: 20
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Country: Number of subjects enrolled |
Turkey: 36
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Country: Number of subjects enrolled |
Ukraine: 60
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Country: Number of subjects enrolled |
United States: 195
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Worldwide total number of subjects |
777
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EEA total number of subjects |
206
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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) |
347
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Adolescents (12-17 years) |
430
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Adults (18-64 years) |
0
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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 150 sites in 17 countries(number of sites with screened/randomised subjects)-Bulgaria: 4/4; Czech Republic: 6/6; Estonia: 2/2; Finland: 3/3; Germany: 6/6; India: 7/7; Israel: 6/6; Italy: 5/5; Japan: 34/34; Latvia: 1/1; Lithuania: 1/1; Poland: 4/4; Russia: 11/11; Serbia: 4/4; Turkey: 7/7; Ukraine: 9/9; United States: 40/39 | ||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
12 week run-in period (834 subjects): Subjects were switched from previous insulin treatment to insulin degludec once daily, and mealtime NovoRapid®/NovoLog®. Insulin degludec treatment was optimised on a weekly basis to the pre-breakfast glycaemic target of 4.0−8.0 mmol/L. 57 subjects were run-in failures and 777 were randomised. | ||||||||||||||||||||||||||||
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 |
The trial was partly double-blinded. The bolus treatment was double-blind for the mealtime faster aspart and NovoRapid®/NovoLog® treatment groups and open-label for the postmeal faster aspart treatment group.
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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 (meal) | ||||||||||||||||||||||||||||
Arm description |
Bolus insulin: Participants received subcutaneous (s.c., into the abdominal wall) injections of faster-acting insulin aspart at mealtime (0−2 minutes before the meal) during 26-week treatment period. Throughout the trial, the insulin was administered at each of the three main meals (i.e. breakfast, lunch and main evening meal). The insulin was titrated to the pre-meal target of 4.0−8.0 mmol/L, and the bed-time target of 6.7–10 mmol/L in a treat-to-target fashion. Basal insulin: Participants continued insulin degludec once daily s.c. injections at the dose optimized during run-in period during 26-week treatment period. Dose adjustment at the discretion of the investigator was allowed if needed. A total of 260 subjects randomized to this arm; however, One subject randomised to the faster aspart (post) group, received mealtime faster aspart throughout the treatment period. Hence, total number of exposed to faster aspart (meal)=261. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Insulin degludec
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Investigational medicinal product code |
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Other name |
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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 |
Insulin degludec was administered once daily, preferably at the same time every day and injected subcutaneously. During the 12-week run-in period, insulin degludec treatment was titrated by the investigator on a weekly basis to the pre-breakfast glycaemic target of 4.0−8.0 mmol/L. During the 26-week treatment period, adjustment at the discretion of the investigator was allowed if needed
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Investigational medicinal product name |
Faster-acting insulin aspart
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Investigational medicinal product code |
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Other name |
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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 |
Faster-acting insulin aspart was administered 0−2 minutes before each of the three main meals (i.e. breakfast, lunch and main evening meal). In the 26-week treatment period, the Faster-acting insulin aspart was titrated to the pre-meal target of 4.0−8.0 mmol/L, and the bed-time target of 6.7–10 mmol/L in a treat-to-target fashion.
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Arm title
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Faster aspart (post) | ||||||||||||||||||||||||||||
Arm description |
Participants received s.c. injections of faster-acting insulin aspart at mealtime (20 minutes after the start of the meal) during 26-week treatment period. Throughout the trial, the insulin was administered at each of the three main meals (i.e. breakfast, lunch and main evening meal). The insulin was titrated to the pre-meal target of 4.0−8.0 mmol/L, and the bed-time target of 6.7–10 mmol/L in a treat-to-target fashion. Basal insulin: Participants continued insulin degludec once daily s.c. injections at the dose optimized during run-in period during 26-week treatment period. Dose adjustment at the discretion of the investigator was allowed if needed. A total of 259 subjects randomized to this arm; however, One subject randomised to this group, received mealtime faster aspart throughout the treatment period. Hence, total number of exposed to faster aspart (post)=258. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Faster-acting insulin aspart
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Investigational medicinal product code |
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Other name |
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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 |
Faster-acting insulin aspart was administered 20 minutes after the start of the meal (i.e. breakfast, lunch and main evening meal). In the 26-week treatment period, the Faster-acting insulin aspart was titrated to the pre-meal target of 4.0−8.0 mmol/L, and the bed-time target of 6.7–10 mmol/L in a treat-to-target fashion.
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Investigational medicinal product name |
Insulin degludec
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Investigational medicinal product code |
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Other name |
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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 |
Insulin degludec was administered once daily, preferably at the same time every day and injected subcutaneously. During the 12-week run-in period, insulin degludec treatment was titrated by the investigator on a weekly basis to the pre-breakfast glycaemic target of 4.0−8.0 mmol/L. During the 26-week treatment period, adjustment at the discretion of the investigator was allowed if needed
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Arm title
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NovoRapid (meal) | ||||||||||||||||||||||||||||
Arm description |
After 12-week run-in period, subjects continued using mealtime insulin aspart (NovoRapid®/NovoLog®) s.c. injections at mealtime (0−2 minutes before the meal) during 26-week treatment period. Throughout the trial, the insulin was administered at each of the three main meals (i.e. breakfast, lunch and main evening meal). The insulin was titrated to the pre-meal target of 4.0−8.0 mmol/L, and the bed-time target of 6.7–10 mmol/L in a treat-to-target fashion. Basal insulin: Participants continued insulin degludec once daily s.c. injections at the dose optimized during run-in period during 26-week treatment period. Dose adjustment at the discretion of the investigator was allowed if needed. | ||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Insulin degludec
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Investigational medicinal product code |
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Other name |
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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 |
Insulin degludec was administered once daily, preferably at the same time every day and injected subcutaneously. During the 12-week run-in period, insulin degludec treatment was titrated by the investigator on a weekly basis to the pre-breakfast glycaemic target of 4.0−8.0 mmol/L. During the 26-week treatment period, adjustment at the discretion of the investigator was allowed if needed
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Investigational medicinal product name |
Insulin aspart
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Investigational medicinal product code |
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Other name |
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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 |
Insulin aspart was administered 0−2 minutes before each of the three main meals (i.e. breakfast, lunch and main evening meal). In the 26-week treatment period, the insulin aspart was titrated to the pre-meal target of 4.0−8.0 mmol/L, and the bed-time target of 6.7–10 mmol/L in a treat-to-target fashion.
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Baseline characteristics reporting groups
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Reporting group title |
Faster aspart (meal)
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Reporting group description |
Bolus insulin: Participants received subcutaneous (s.c., into the abdominal wall) injections of faster-acting insulin aspart at mealtime (0−2 minutes before the meal) during 26-week treatment period. Throughout the trial, the insulin was administered at each of the three main meals (i.e. breakfast, lunch and main evening meal). The insulin was titrated to the pre-meal target of 4.0−8.0 mmol/L, and the bed-time target of 6.7–10 mmol/L in a treat-to-target fashion. Basal insulin: Participants continued insulin degludec once daily s.c. injections at the dose optimized during run-in period during 26-week treatment period. Dose adjustment at the discretion of the investigator was allowed if needed. A total of 260 subjects randomized to this arm; however, One subject randomised to the faster aspart (post) group, received mealtime faster aspart throughout the treatment period. Hence, total number of exposed to faster aspart (meal)=261. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Faster aspart (post)
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Reporting group description |
Participants received s.c. injections of faster-acting insulin aspart at mealtime (20 minutes after the start of the meal) during 26-week treatment period. Throughout the trial, the insulin was administered at each of the three main meals (i.e. breakfast, lunch and main evening meal). The insulin was titrated to the pre-meal target of 4.0−8.0 mmol/L, and the bed-time target of 6.7–10 mmol/L in a treat-to-target fashion. Basal insulin: Participants continued insulin degludec once daily s.c. injections at the dose optimized during run-in period during 26-week treatment period. Dose adjustment at the discretion of the investigator was allowed if needed. A total of 259 subjects randomized to this arm; however, One subject randomised to this group, received mealtime faster aspart throughout the treatment period. Hence, total number of exposed to faster aspart (post)=258. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NovoRapid (meal)
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Reporting group description |
After 12-week run-in period, subjects continued using mealtime insulin aspart (NovoRapid®/NovoLog®) s.c. injections at mealtime (0−2 minutes before the meal) during 26-week treatment period. Throughout the trial, the insulin was administered at each of the three main meals (i.e. breakfast, lunch and main evening meal). The insulin was titrated to the pre-meal target of 4.0−8.0 mmol/L, and the bed-time target of 6.7–10 mmol/L in a treat-to-target fashion. Basal insulin: Participants continued insulin degludec once daily s.c. injections at the dose optimized during run-in period during 26-week treatment period. Dose adjustment at the discretion of the investigator was allowed if needed. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Faster aspart (meal)
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Reporting group description |
Bolus insulin: Participants received subcutaneous (s.c., into the abdominal wall) injections of faster-acting insulin aspart at mealtime (0−2 minutes before the meal) during 26-week treatment period. Throughout the trial, the insulin was administered at each of the three main meals (i.e. breakfast, lunch and main evening meal). The insulin was titrated to the pre-meal target of 4.0−8.0 mmol/L, and the bed-time target of 6.7–10 mmol/L in a treat-to-target fashion. Basal insulin: Participants continued insulin degludec once daily s.c. injections at the dose optimized during run-in period during 26-week treatment period. Dose adjustment at the discretion of the investigator was allowed if needed. A total of 260 subjects randomized to this arm; however, One subject randomised to the faster aspart (post) group, received mealtime faster aspart throughout the treatment period. Hence, total number of exposed to faster aspart (meal)=261. | ||
Reporting group title |
Faster aspart (post)
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Reporting group description |
Participants received s.c. injections of faster-acting insulin aspart at mealtime (20 minutes after the start of the meal) during 26-week treatment period. Throughout the trial, the insulin was administered at each of the three main meals (i.e. breakfast, lunch and main evening meal). The insulin was titrated to the pre-meal target of 4.0−8.0 mmol/L, and the bed-time target of 6.7–10 mmol/L in a treat-to-target fashion. Basal insulin: Participants continued insulin degludec once daily s.c. injections at the dose optimized during run-in period during 26-week treatment period. Dose adjustment at the discretion of the investigator was allowed if needed. A total of 259 subjects randomized to this arm; however, One subject randomised to this group, received mealtime faster aspart throughout the treatment period. Hence, total number of exposed to faster aspart (post)=258. | ||
Reporting group title |
NovoRapid (meal)
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Reporting group description |
After 12-week run-in period, subjects continued using mealtime insulin aspart (NovoRapid®/NovoLog®) s.c. injections at mealtime (0−2 minutes before the meal) during 26-week treatment period. Throughout the trial, the insulin was administered at each of the three main meals (i.e. breakfast, lunch and main evening meal). The insulin was titrated to the pre-meal target of 4.0−8.0 mmol/L, and the bed-time target of 6.7–10 mmol/L in a treat-to-target fashion. Basal insulin: Participants continued insulin degludec once daily s.c. injections at the dose optimized during run-in period during 26-week treatment period. Dose adjustment at the discretion of the investigator was allowed if needed. |
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End point title |
Change from baseline in HbA1c | ||||||||||||||||
End point description |
Change from baseline (week 0) in HbA1c was evaluated after 26 weeks of 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. Analysis was based on full analysis set (FAS) which includes all randomised subjects. Number of subjects analysed=subject with data available for HbA1c.
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End point type |
Primary
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End point timeframe |
26 weeks after randomisation
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Statistical analysis title |
Faster aspart (meal) vs. NovoRapid (meal) | ||||||||||||||||
Statistical analysis description |
The primary analysis was implemented as a statistical model using multiple imputation where the subjects without any available HbA1c measurements at scheduled visits had their change from baseline HbA1c value(s) imputed from the available information from the treatment the subject had been randomised to.
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Comparison groups |
Faster aspart (meal) v NovoRapid (meal)
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Number of subjects included in analysis |
518
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||||||
P-value |
< 0.001 [2] | ||||||||||||||||
Method |
multiple imputation | ||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||
Point estimate |
-0.17
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-0.3 | ||||||||||||||||
upper limit |
-0.03 | ||||||||||||||||
Notes [1] - Stepwise hierarchical testing procedure was applied: Step 1-Primary analysis: HbA1c non-inferiority of mealtime faster aspart versus mealtime NovoRapid®/NovoLog® both in combination with insulin degludec. Non-inferiority of mealtime faster aspart was considered confirmed if the upper boundary of the two-sided 95% CI was below or equal to 0.4%. [2] - p-values are from the 1-sided test for non-inferiority evaluated at the 2.5% level. |
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Statistical analysis title |
Faster aspart (post) vs. NovoRapid (meal) | ||||||||||||||||
Statistical analysis description |
The analysis was implemented as a statistical model using multiple imputation where the subjects without any available HbA1c measurements at scheduled visits had their change from baseline HbA1c value(s) imputed from the available information from the treatment the subject had been randomised to.
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Comparison groups |
Faster aspart (post) v NovoRapid (meal)
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Number of subjects included in analysis |
517
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | ||||||||||||||||
P-value |
< 0.001 [4] | ||||||||||||||||
Method |
multiple imputation | ||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||
Point estimate |
0.13
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-0.01 | ||||||||||||||||
upper limit |
0.26 | ||||||||||||||||
Notes [3] - Stepwise hierarchical testing procedure was applied: Step 2-Confirmatory secondary analysis: HbA1c non-inferiority of postmeal faster aspart versus mealtime NovoRapid®/NovoLog® both in combination with insulin degludec. Non-inferiority of mealtime faster aspart was considered confirmed if the upper boundary of the two-sided 95% CI was below or equal to 0.4%. [4] - p-values are from the 1-sided test for non-inferiority evaluated at the 2.5% level. |
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Statistical analysis title |
Faster aspart (meal) vs. NovoRapid (meal) | ||||||||||||||||
Statistical analysis description |
The analysis was implemented as a statistical model using multiple imputation where the subjects without any available HbA1c measurements at scheduled visits had their change from baseline HbA1c value(s) imputed from the available information from the treatment the subject had been randomised to.
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Comparison groups |
Faster aspart (meal) v NovoRapid (meal)
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Number of subjects included in analysis |
518
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Analysis specification |
Pre-specified
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Analysis type |
superiority [5] | ||||||||||||||||
P-value |
= 0.007 [6] | ||||||||||||||||
Method |
multiple imputation | ||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||
Point estimate |
-0.17
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-0.3 | ||||||||||||||||
upper limit |
-0.03 | ||||||||||||||||
Notes [5] - Stepwise hierarchical testing procedure was applied: Step 3-Confirmatory secondary analysis: HbA1c superiority of mealtime faster aspart versus mealtime NovoRapid®/NovoLog® both in combination with insulin degludec. Superiority of mealtime faster aspart was considered confirmed if the upper boundary of the two-sided 95% CI was below 0. [6] - p-values are from the 1-sided test for superiority evaluated at the 2.5% level. |
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End point title |
Change from baseline in 8-point self-measured plasma glucose (SMPG) profile (8-point profile): - Mean postprandial glucose (PPG) and PPG increment over all three meals | ||||||||||||||||||||||||
End point description |
SMPG values were recorded at 8 time-points: before and after (60 min after the start of the meal) breakfast, lunch, main evening meal, before bedtime, and before breakfast on the next day. PPG was recorded by the subject as part of the two 8-point profiles prior to the visits. PPG increments based on the 8-point profiles were derived separately for PG measurements made 1 hour after the meal. PPG increment for each meal (breakfast, lunch, main evening meal) was derived from the 8-point profile as the difference between PPG values and the PG value before meal. 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. Analysis was based on FAS. Number of subjects analysed=subjects who contributed to the analysis.
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End point type |
Secondary
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End point timeframe |
26 weeks after randomisation
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No statistical analyses for this end point |
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End point title |
Change from baseline in fasting plasma glucose (FPG) | ||||||||||||||||
End point description |
Change from baseline (week 0) in FPG was evaluated after 26 weeks of 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. Analysis was based on FAS. Number of subjects analysed=subject with data available for FPG.
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End point type |
Secondary
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End point timeframe |
26 weeks after randomisation
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No statistical analyses for this end point |
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End point title |
Number of treatment emergent adverse events (AEs) | ||||||||||||||||
End point description |
Treatment emergent is defined as an event that has onset up to 7 days after last day of randomised treatment and excluding the events occurring in the run-in period. Results are presented as event rate per 100 patient years of exposure (PYE). Safety analysis set (SAS) includes all subjects receiving at least one dose of the investigational product or its comparator. Subjects in the safety set will contribute to the evaluation “as treated”. One subject was randomised to the postmeal faster aspart group but was exposed to mealtime faster aspart throughout the treatment period. The subject was included in the mealtime faster aspart group for the safety analysis set. Therefore, number of subjects analysed= 261 for Faster aspart (meal), 258 for Faster aspart (post) and 258 for NovoRapid (meal).
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End point type |
Secondary
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End point timeframe |
26 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 |
From randomization (week 0) to week 26 + 7 days of follow-up
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 (meal)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Faster aspart (post)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NovoRapid (meal)
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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? Yes | |||
Date |
Amendment |
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18 Mar 2016 |
Added ‘or equal to’ in the definition of confirming of non-inferiority in trial protocol |
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06 Jun 2016 |
A mistake identified in the blood sampling volume at visit 14 and visit 40 for the subjects participating in the Continuous lucose Monitoring (CGM) and meal test subgroup. Consequently the required minimum weight for participation in the CGM and meal test subgroup was increased to ensure the blood volume collected at visit 14 and visit 40 did not exceed 1% of the subjects total blood volume. |
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25 Feb 2017 |
1. An inaccuracy was identified in the layman language for reporting hypoglycaemic episodes. There was a need to clarify the run-in failure criteria, to provide more guidance on when to report a MESI, and that the FPG sample was to be collected using the FPG home sampling kit no matter if the FPG sample was taken at home or at site. 2. The statistical section was updated to clarify the analyses made for the primary and secondary estimands, the supportive secondary CGM and meal test related efficacy endpoints. A clarification was made to which treatment emergent hypoglycaemic episodes should be included in the analyses. 3. An appendix was updated to reflect the changes that occurred due to the change in CGM supplier shortly before trial initiation. |
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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 |