Trial Outcomes & Findings for 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 (NCT NCT01999322)

NCT ID: NCT01999322

Last Updated: 2017-10-31

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

37 participants

Primary outcome timeframe

During 6 weeks of treatment

Results posted on

2017-10-31

Participant Flow

The trial was conducted at two sites in two countries as follows: USA: one site; Germany: one site.

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.

Participant milestones

Participant milestones
Measure	Faster-acting Insulin Aspart 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.	NovoRapid® 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 Study STARTED	25	12
Overall Study COMPLETED	24	12
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Faster-acting Insulin Aspart 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.	NovoRapid® 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 Study Adverse Event	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Faster-acting Insulin Aspart n=25 Participants 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.	NovoRapid® n=12 Participants 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 n=37 Participants Total of all reporting groups
Age, Continuous	48.9 years STANDARD_DEVIATION 14.6 • n=5 Participants	34.7 years STANDARD_DEVIATION 9.1 • n=7 Participants	44.3 years STANDARD_DEVIATION 14.6 • n=5 Participants
Age, Customized 18-64	19 participants n=5 Participants	12 participants n=7 Participants	31 participants n=5 Participants
Age, Customized 65-84	6 participants n=5 Participants	0 participants n=7 Participants	6 participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	4 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	8 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: During 6 weeks of treatment

Population: 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".

Outcome measures

Outcome measures
Measure	Faster-acting Insulin Aspart n=25 Participants 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.	NovoRapid® n=12 Participants 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).
Number of Microscopically Confirmed Episodes of Infusion Set Occlusions	0 Episodes	0 Episodes

SECONDARY outcome

Timeframe: During 6 weeks of treatment

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)

Outcome measures

Outcome measures
Measure	Faster-acting Insulin Aspart n=25 Participants 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.	NovoRapid® n=12 Participants 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).
Number of Unexplained Episodes of Hyperglycaemia (Confirmed by Self-measured Plasma Glucose (SMPG))	28 events	16 events

SECONDARY outcome

Timeframe: During 6 weeks of treatment

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.

Outcome measures

Outcome measures
Measure	Faster-acting Insulin Aspart n=25 Participants 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.	NovoRapid® n=12 Participants 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).
Number of Episodes of Possible Infusion Set Occlusions	7 Episodes	0 Episodes

SECONDARY outcome

Timeframe: During 6 weeks of treatment

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.

Outcome measures

Outcome measures
Measure	Faster-acting Insulin Aspart n=25 Participants 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.	NovoRapid® n=12 Participants 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).
Number of Premature Infusion Set Changes	21 Episodes	4 Episodes

Adverse Events

Faster-acting Insulin Aspart

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

NovoRapid®

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Global Clinical Registry (GCR, 1452)

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee "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"
Publication restrictions are in place

Restriction type: OTHER

Measure	Faster-acting Insulin Aspart n=25 participants at risk 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.	NovoRapid® n=12 participants at risk 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).
Musculoskeletal and connective tissue disorders Back pain	8.0% 2/25 • Number of events 3 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	0.00% 0/12 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Cough	4.0% 1/25 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	16.7% 2/12 • Number of events 2 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Eye disorders Diabetic retinopathy	0.00% 0/25 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	8.3% 1/12 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
General disorders Influenza like illness	8.0% 2/25 • Number of events 2 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	0.00% 0/12 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Infections and infestations Nasopharyngitis	12.0% 3/25 • Number of events 3 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	8.3% 1/12 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/25 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	16.7% 2/12 • Number of events 2 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Infections and infestations Otitis media	0.00% 0/25 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	8.3% 1/12 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/25 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	8.3% 1/12 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
General disorders Pyrexia	4.0% 1/25 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	8.3% 1/12 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Skin and subcutaneous tissue disorders Rash	0.00% 0/25 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	8.3% 1/12 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/25 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	8.3% 1/12 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Infections and infestations Sinusitis	0.00% 0/25 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	8.3% 1/12 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Infections and infestations Tonsillitis	0.00% 0/25 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	8.3% 1/12 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	0.00% 0/25 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	8.3% 1/12 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.
Infections and infestations Upper respiratory tract infection	0.00% 0/25 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.	8.3% 1/12 • Number of events 1 • 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. Safety Analysis Set: includes all subjects receiving at least one dose of the investigational product or its comparator.