Clinical Trial Results:
A 6-week randomised, double-blind, parallel-group trial evaluating compatibility and safety of FIAsp and insulin aspart with an external continuous subcutaneous insulin infusion system in adult subjects with type 1 diabetes
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Summary
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EudraCT number |
2013-002233-37 |
Trial protocol |
DE |
Global end of trial date |
14 May 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Apr 2016
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First version publication date |
26 Jul 2015
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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 |
NN1218-3931
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01999322 | ||
WHO universal trial number (UTN) |
U1111-1143-2316 | ||
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Sponsors
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Sponsor organisation name |
Novo Nordisk A/S
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Sponsor organisation address |
Novo Allè, Bagsvaerd, Denmark, 2860
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Public contact |
Global Clinical Registry (GCR,1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Scientific contact |
Global Clinical Registry (GCR,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 |
12 Feb 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 May 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
14 May 2014
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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 evaluate the compatibility of faster-acting insulin aspart (FIAsp) and insulin aspart with the external continuous subcutaneous insulin infusion (CSII) system over a 6-week treatment period.
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Protection of trial subjects |
The trial was conducted in accordance with the Declaration of Helsinki and ICH Good Clinical Practice and 21 CFR 312.120.
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Background therapy |
Eligible subjects previously treated with a rapid-acting insulin analogue were to stay on their own NovoRapid®, insulin lispro or insulin glulisine in the screening period, after which all subjects received NovoRapid®, with no additional anti-diabetes treatment allowed, for a 2-week run-in period prior to randomisation. | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
19 Nov 2013
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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 |
United States: 10
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Country: Number of subjects enrolled |
Germany: 27
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Worldwide total number of subjects |
37
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EEA total number of subjects |
27
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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) |
31
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From 65 to 84 years |
6
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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 two sites in two countries as follows: USA: one site; Germany one site. | |||||||||||||||
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Pre-assignment
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Screening details |
Eligible subjects previously treated with a rapid acting insulin analogue were to stay in their own NovoRapid®, insulin lispro or insulin glulisine in the screening period after which the all subjects received NovoRapid®, with no additional antidiabetics allowed, for a 2-week run-in period prior to randomisation. | |||||||||||||||
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Period 1
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Period 1 title |
Period 1 (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 |
This trial was double-blinded. The randomisation in this study was 2:1.
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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-acting insulin aspart | |||||||||||||||
Arm description |
Subjects received faster-acting insulin aspart for a duration of 6 weeks. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: pre-prandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2-hr postprandial glucose: below 7.8 mmol/L (140 mg/dL). A 2:1 randomisation following the screening period was selected in order to ensure adequate exposure to faster-acting insulin aspart. | |||||||||||||||
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 |
INSULIN ASPART
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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 provided in 100U/ml 3 mL Penfill® and administered in accordance with the instructions provided by the pump manufacturer, preferably in the abdomen by subcutaneous infusion. Subjects were instructed in how to fill the reservoir from Penfill®. The subjects remained on their own external CSII system. Subjects were instructed to change infusion set and reservoir every 72 hours (± 4 hours) and only before 72 hours (± 4 hours) if there is any suspicion of occlusion, leakage, unexplained hyperglycaemic episode, infusion site reaction, technical reason or other reason. Infusion sites were to be rotated but the infusion set was to be inserted in a standardised way in a similar position. No maximum dose was specified. Doses were adjusted according to plasma glucose and the bolus dose was calculated manually or by using pump bolus calculator.
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Arm title
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NovoRapid® | |||||||||||||||
Arm description |
Subjects received NovoRapid® for a duration of 6 weeks. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: pre-prandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2-hr postprandial glucose: below 7.8 mmol/L (140 mg/dL). | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
NovoRapid®
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Investigational medicinal product code |
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Other name |
INSULIN ASPART
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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 |
NovoRapid® was provided in 100U/ml 3 ml Penfill® and administered in accordance with the instructions provided by the pump manufacturer, preferably in the abdomen by subcutaneous infusion. The subjects remained on their own external CSII system. Subjects were instructed to change infusion set and reservoir every 72 hours (± 4 hours) and only before 72 hours (± 4 hours) if there is any suspicion of occlusion, leakage, unexplained hyperglycaemic episode, infusion site reaction, technical reason or other reason. Infusion sites were to be rotated but the infusion set was to be inserted in a standardised way in a similar position. No maximum dose was specified. Doses were adjusted according to plasma glucose and the bolus dose was calculated manually or by using pump bolus calcualtor.
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Baseline characteristics reporting groups
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Reporting group title |
Faster-acting insulin aspart
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Reporting group description |
Subjects received faster-acting insulin aspart for a duration of 6 weeks. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: pre-prandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2-hr postprandial glucose: below 7.8 mmol/L (140 mg/dL). A 2:1 randomisation following the screening period was selected in order to ensure adequate exposure to faster-acting insulin aspart. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NovoRapid®
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Reporting group description |
Subjects received NovoRapid® for a duration of 6 weeks. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: pre-prandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2-hr postprandial glucose: below 7.8 mmol/L (140 mg/dL). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Faster-acting insulin aspart
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Reporting group description |
Subjects received faster-acting insulin aspart for a duration of 6 weeks. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: pre-prandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2-hr postprandial glucose: below 7.8 mmol/L (140 mg/dL). A 2:1 randomisation following the screening period was selected in order to ensure adequate exposure to faster-acting insulin aspart. | ||
Reporting group title |
NovoRapid®
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Reporting group description |
Subjects received NovoRapid® for a duration of 6 weeks. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: pre-prandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2-hr postprandial glucose: below 7.8 mmol/L (140 mg/dL). | ||
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End point title |
Number of microscopically confirmed episodes of infusion set occlusions. [1] | |||||||||
End point description |
Microscopy was conducted at the laboratory at routine weekly site visits and if the infusion set was sent in by the subject following a premature change because of leakage, unexplained hyperglycaemia or suspicion of occlusion (observation of a plug).
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End point type |
Primary
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End point timeframe |
6 weeks of treatment
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no specification of an analysis in the protocol or in the statistical analysis plan. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of unexplained episodes of hyperglycaemia | |||||||||
End point description |
Unexplained hyperglycaemia was defined as a confirmed plasma glucose value ≥ 16.7 mmol/L (300 mg/dL) and was unexplained (i.e., no apparent medical, dietary, insulin dosage or pump failure reason)
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End point type |
Secondary
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End point timeframe |
During 6 weeks of treatment
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of possible infusion set occlusions | |||||||||
End point description |
Episodes of possible infusion set occlusions were defined as infusion sets changed due to suspicion of occlusion, leakage or unexplained hyperglycaemic episode. Possible occlusion excluded technical reasons. This endpoint was calculated from the recorded date/times of changes of infusion set combined with the subjects’ own assessment.
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End point type |
Secondary
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End point timeframe |
During 6 weeks of treatment
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of premature infusion set changes | |||||||||
End point description |
A premature infusion set change was defined as not being a routine change. This was defined as an infusion set changed at home due to "suspicion of occlusion", "leakage", "unexplained hyperglycaemic episode", "infusion site reaction", "technical reason", or "other". The change of infusion set at a site visit was considered a routine change unless an occlusion was actually suspected at the site.
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End point type |
Secondary
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End point timeframe |
During 6 weeks of treatment.
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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 |
SAEs to be reported within 24 hours.
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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 |
17
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Reporting groups
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Reporting group title |
NovoRapid®
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Reporting group description |
Subjects received NovoRapid® for a duration of 6 weeks. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: pre-prandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2-hr postprandial glucose: below 7.8 mmol/L (140 mg/dL). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Faster-acting insulin aspart
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Reporting group description |
Subjects received faster-acting insulin aspart for a duration of 6 weeks. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: pre-prandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2-hr postprandial glucose: below 7.8 mmol/L (140 mg/dL). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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. | |||
| The trial was designed in accordance with the draft FDA guideline dated 1985, that 15−20 subjects with diabetes given the modified insulin should be included for 6 weeks. However the trial was not powered to detect differences between treatments. | |||
