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A 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 (onset® 4)

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ClinicalTrials.gov Identifier: NCT01999322
Recruitment Status : Completed
First Posted : December 3, 2013
Results First Posted : October 31, 2017
Last Update Posted : October 31, 2017
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Diabetes
Diabetes Mellitus, Type 1
Interventions Drug: Faster-acting insulin aspart
Drug: insulin aspart
Enrollment 37
Recruitment Details The trial was conducted at two sites in two countries as follows: USA: one site; Germany: one site.
Pre-assignment Details 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 the all subjects received NovoRapid®, with no additional antidiabetics allowed, for a 2-week run-in period prior to randomisation.
Arm/Group Title Faster-acting Insulin Aspart NovoRapid®
Hide Arm/Group Description Subjects received faster-acting insulin aspart for a duration of 6 weeks. 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. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial 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. Subjects received NovoRapid® for a duration of 6 weeks. 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 insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2 hr postprandial glucose: below 7.8 mmol/L (140 mg/dL).
Period Title: Overall Study
Started 25 12
Completed 24 12
Not Completed 1 0
Reason Not Completed
Adverse Event             1             0
Arm/Group Title Faster-acting Insulin Aspart NovoRapid® Total
Hide Arm/Group Description Subjects received faster-acting insulin aspart for a duration of 6 weeks. 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. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial 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. Subjects received NovoRapid® for a duration of 6 weeks. 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 insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2 hr postprandial glucose: below 7.8 mmol/L (140 mg/dL). Total of all reporting groups
Overall Number of Baseline Participants 25 12 37
Hide Baseline Analysis Population Description
Full Analysis Set: included all randomised subjects. In exceptional cases subjects could be excluded from the full analysis set. In such cases the reason for exclusion was to be justified and documented. Safety analysis set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants 12 participants 37 participants
48.9  (14.6) 34.7  (9.1) 44.3  (14.6)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants 12 participants 37 participants
18-64 19 12 31
65-84 6 0 6
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 12 participants 37 participants
Female
11
  44.0%
4
  33.3%
15
  40.5%
Male
14
  56.0%
8
  66.7%
22
  59.5%
1.Primary Outcome
Title Number of Microscopically Confirmed Episodes of Infusion Set Occlusions
Hide Description The number of microscopically confirmed episodes of infusion set occlusions during 6 weeks of treatment. Episodes of infusion set occlusions were confirmed by microscopic examination of the infusion sets at each routine weekly visit and infusion sets that had been changed prematurely because of leakage, unexplained hyperglycaemia or suspicion of occlusion (observation of a plug).
Time Frame During 6 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: included all randomised subjects. In exceptional cases subjects could be excluded from the full analysis set. In such cases the reason for exclusion was to be justified and documented. Subjects in the full analysis set contribute to the evaluation “as randomised”.
Arm/Group Title Faster-acting Insulin Aspart NovoRapid®
Hide Arm/Group Description:
Subjects received faster-acting insulin aspart for a duration of 6 weeks. 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. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial 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.
Subjects received NovoRapid® for a duration of 6 weeks. 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 insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2 hr postprandial glucose: below 7.8 mmol/L (140 mg/dL).
Overall Number of Participants Analyzed 25 12
Measure Type: Number
Unit of Measure: Episodes
0 0
2.Secondary Outcome
Title Number of Unexplained Episodes of Hyperglycaemia (Confirmed by Self-measured Plasma Glucose (SMPG))
Hide 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)
Time Frame During 6 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Faster-acting Insulin Aspart NovoRapid®
Hide Arm/Group Description:
Subjects received faster-acting insulin aspart for a duration of 6 weeks. 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. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial 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.
Subjects received NovoRapid® for a duration of 6 weeks. 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 insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2 hr postprandial glucose: below 7.8 mmol/L (140 mg/dL).
Overall Number of Participants Analyzed 25 12
Measure Type: Number
Unit of Measure: events
28 16
3.Secondary Outcome
Title Number of Episodes of Possible Infusion Set Occlusions
Hide 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.
Time Frame During 6 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Faster-acting Insulin Aspart NovoRapid®
Hide Arm/Group Description:
Subjects received faster-acting insulin aspart for a duration of 6 weeks. 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. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial 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.
Subjects received NovoRapid® for a duration of 6 weeks. 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 insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2 hr postprandial glucose: below 7.8 mmol/L (140 mg/dL).
Overall Number of Participants Analyzed 25 12
Measure Type: Number
Unit of Measure: Episodes
7 0
4.Secondary Outcome
Title Number of Premature Infusion Set Changes
Hide 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.
Time Frame During 6 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Faster-acting Insulin Aspart NovoRapid®
Hide Arm/Group Description:
Subjects received faster-acting insulin aspart for a duration of 6 weeks. 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. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial 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.
Subjects received NovoRapid® for a duration of 6 weeks. 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 insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2 hr postprandial glucose: below 7.8 mmol/L (140 mg/dL).
Overall Number of Participants Analyzed 25 12
Measure Type: Number
Unit of Measure: Episodes
21 4
Time Frame A treatment emergent adverse event is defined as en event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.
Adverse Event Reporting Description Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
 
Arm/Group Title Faster-acting Insulin Aspart NovoRapid®
Hide Arm/Group Description Subjects received faster-acting insulin aspart for a duration of 6 weeks. 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. The insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial 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. Subjects received NovoRapid® for a duration of 6 weeks. 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 insulin dose adjustments were made based on frequent glucose measurements during contacts with the investigator. The following glycaemic targets were recommended: preprandial and bedtime glucose: below 6.0 mmol/L (108 mg/dL) and 2 hr postprandial glucose: below 7.8 mmol/L (140 mg/dL).
All-Cause Mortality
Faster-acting Insulin Aspart NovoRapid®
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Faster-acting Insulin Aspart NovoRapid®
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/25 (0.00%)      0/12 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Faster-acting Insulin Aspart NovoRapid®
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/25 (36.00%)      6/12 (50.00%)    
Eye disorders     
Diabetic retinopathy  1  0/25 (0.00%)  0 1/12 (8.33%)  1
General disorders     
Influenza like illness  1  2/25 (8.00%)  2 0/12 (0.00%)  0
Pyrexia  1  1/25 (4.00%)  1 1/12 (8.33%)  1
Infections and infestations     
Nasopharyngitis  1  3/25 (12.00%)  3 1/12 (8.33%)  1
Otitis media  1  0/25 (0.00%)  0 1/12 (8.33%)  1
Sinusitis  1  0/25 (0.00%)  0 1/12 (8.33%)  1
Tonsillitis  1  0/25 (0.00%)  0 1/12 (8.33%)  1
Upper respiratory tract infection  1  0/25 (0.00%)  0 1/12 (8.33%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  2/25 (8.00%)  3 0/12 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/25 (4.00%)  1 2/12 (16.67%)  2
Oropharyngeal pain  1  0/25 (0.00%)  0 2/12 (16.67%)  2
Sinus congestion  1  0/25 (0.00%)  0 1/12 (8.33%)  1
Upper respiratory tract congestion  1  0/25 (0.00%)  0 1/12 (8.33%)  1
Skin and subcutaneous tissue disorders     
Pruritus  1  0/25 (0.00%)  0 1/12 (8.33%)  1
Rash  1  0/25 (0.00%)  0 1/12 (8.33%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
“At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property”
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Registry (GCR, 1452)
Organization: Novo Nordisk A/S
EMail: clinicaltrials@novonordisk.com
Publications of Results:
Eric Zijlstra, Marek Demissie et al. Compatibility and Safety of Faster-Acting Insulin Aspart used in Continuous Subcutaneous Insulin Infusion Therapy in Patients with Type 1 Diabetes. ENDO-2016-98th Annual Meeting of the Endocrine Society 3 June 2016 http://press.endocrine.org/doi/abs/10.1210.endo-meetings.2016.DGM.22.FRI-697
Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01999322     History of Changes
Other Study ID Numbers: NN1218-3931
2013-002233-37 ( EudraCT Number )
U1111-1143-2316 ( Other Identifier: WHO )
First Submitted: November 25, 2013
First Posted: December 3, 2013
Results First Submitted: October 2, 2017
Results First Posted: October 31, 2017
Last Update Posted: October 31, 2017