Diabetes, Diabetes Mellitus, Type 1
Conditions
Brief summary
This trial is conducted in Europe and the United States of America (USA). The aim of this trial is to evaluate compatibility and safety of FIAsp (faster-acting insulin aspart) and insulin aspart (NovoRapid®) with an external continuous subcutaneous insulin infusion (CSII) system in adult subjects with type 1 diabetes.
Interventions
DRUGFaster-acting insulin aspart
Administered subcutaneously (s.c., under the skin). Dose individually adjusted.
DRUGinsulin aspart
Administered subcutaneously (s.c., under the skin). Dose individually adjusted.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, age at least 18 years at the time of signing inform consent * Type 1 diabetes mellitus (diagnosed clinically) for at least 12 months at the time of screening (Visit 1) * Currently treated with insulin aspart, insulin lispro or insulin gluisine for at least 3 months prior to screening (Visit 1) * Using an external CSII system for the previous 6 months prior to screening (Visit 1) * HbA1c (glycosylated haemoglobin) below or equal to 9.0% as assessed by central laboratory * Body Mass Index (BMI) 20.0-35.0 kg/m\^2
Exclusion criteria
* History of diabetic ketoacidosis (DKA) episodes requiring hospitalization within 6 months prior to screening (Visit 1) * History of abscess at the infusion site within 6 months prior to screening (Visit 1) * Hypoglycaemic unawareness as judged by the Investigator or history of severe hypoglycaemic episodes requiring hospitalization within the last 6 months prior to screening (Visit 1)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Microscopically Confirmed Episodes of Infusion Set Occlusions | During 6 weeks of treatment | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Unexplained Episodes of Hyperglycaemia (Confirmed by Self-measured Plasma Glucose (SMPG)) | 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) |
| Number of Episodes of Possible Infusion Set Occlusions | 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. |
| Number of Premature Infusion Set Changes | 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. |
Countries
Germany, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 25 |
| 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). | 12 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Faster-acting Insulin Aspart | NovoRapid® | Total |
|---|---|---|---|
| Age, Continuous | 48.9 years STANDARD_DEVIATION 14.6 | 34.7 years STANDARD_DEVIATION 9.1 | 44.3 years STANDARD_DEVIATION 14.6 |
| Age, Customized 18-64 | 19 participants | 12 participants | 31 participants |
| Age, Customized 65-84 | 6 participants | 0 participants | 6 participants |
| Sex: Female, Male Female | 11 Participants | 4 Participants | 15 Participants |
| Sex: Female, Male Male | 14 Participants | 8 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 25 | 6 / 12 |
| serious Total, serious adverse events | 0 / 25 | 0 / 12 |
Outcome results
Primary
Number of Microscopically Confirmed Episodes of Infusion Set Occlusions
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
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Faster-acting Insulin Aspart | Number of Microscopically Confirmed Episodes of Infusion Set Occlusions | 0 Episodes |
| NovoRapid® | Number of Microscopically Confirmed Episodes of Infusion Set Occlusions | 0 Episodes |
Secondary
Number of Episodes of Possible Infusion Set Occlusions
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Faster-acting Insulin Aspart | Number of Episodes of Possible Infusion Set Occlusions | 7 Episodes |
| NovoRapid® | Number of Episodes of Possible Infusion Set Occlusions | 0 Episodes |
Secondary
Number of Premature Infusion Set Changes
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Faster-acting Insulin Aspart | Number of Premature Infusion Set Changes | 21 Episodes |
| NovoRapid® | Number of Premature Infusion Set Changes | 4 Episodes |
Secondary
Number of Unexplained Episodes of Hyperglycaemia (Confirmed by Self-measured Plasma Glucose (SMPG))
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Faster-acting Insulin Aspart | Number of Unexplained Episodes of Hyperglycaemia (Confirmed by Self-measured Plasma Glucose (SMPG)) | 28 events |
| NovoRapid® | Number of Unexplained Episodes of Hyperglycaemia (Confirmed by Self-measured Plasma Glucose (SMPG)) | 16 events |