onset® 4: 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
Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT01999322
Collaborator
(none)
37
2
2
5.8
18.5
3.2
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
37 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date
:
Nov 19, 2013
Actual Primary Completion Date
:
May 14, 2014
Actual Study Completion Date
:
May 14, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: FIAsp The trial duration is approximately 13 weeks and consists of a 1-week screening period, a 2-week run-in period, a 6-week treatment period and 1 week plus a 30-day follow-up period |
Drug: Faster-acting insulin aspart
Administered subcutaneously (s.c., under the skin). Dose individually adjusted.
|
| Active Comparator: Insulin Aspart The trial duration is approximately 13 weeks and consists of a 1-week screening period, a 2-week run-in period, a 6-week treatment period and 1 week plus a 30-day follow-up period |
Drug: insulin aspart
Administered subcutaneously (s.c., under the skin). Dose individually adjusted.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novo Nordisk Investigational Site | Atlanta | Georgia | United States | 30318 |
| 2 | Novo Nordisk Investigational Site | Neuss | Germany | 41460 |
Sponsors and Collaborators
- Novo Nordisk A/S
Investigators
- Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01999322
Other Study ID Numbers:
- NN1218-3931
- 2013-002233-37
- U1111-1143-2316
First Posted:
Dec 3, 2013
Last Update Posted:
Oct 31, 2017
Last Verified:
Oct 1, 2017
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The trial was conducted at two sites in two countries as follows: USA: one site; Germany: one site. |
|---|---|
| Pre-assignment Detail | 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® |
|---|---|---|
| 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 |
Baseline Characteristics
| Arm/Group Title | Faster-acting Insulin Aspart | NovoRapid® | Total |
|---|---|---|---|
| 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 Participants | 25 | 12 | 37 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
48.9
(14.6)
|
34.7
(9.1)
|
44.3
(14.6)
|
| Age, Customized (participants) [Number] | |||
| 18-64 |
19
76%
|
12
100%
|
31
83.8%
|
| 65-84 |
6
24%
|
0
0%
|
6
16.2%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
11
44%
|
4
33.3%
|
15
40.5%
|
| Male |
14
56%
|
8
66.7%
|
22
59.5%
|
Outcome Measures
| Title | Number of Microscopically Confirmed Episodes of Infusion Set Occlusions |
|---|---|
| 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 |
Outcome Measure Data
| 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® |
|---|---|---|
| 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). |
| Measure Participants | 25 | 12 |
| Number [Episodes] |
0
|
0
|
| Title | Number of Unexplained Episodes of Hyperglycaemia (Confirmed by Self-measured Plasma Glucose (SMPG)) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Faster-acting Insulin Aspart | NovoRapid® |
|---|---|---|
| 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). |
| Measure Participants | 25 | 12 |
| Number [events] |
28
|
16
|
| Title | Number of Episodes of Possible Infusion Set Occlusions |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Faster-acting Insulin Aspart | NovoRapid® |
|---|---|---|
| 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). |
| Measure Participants | 25 | 12 |
| Number [Episodes] |
7
|
0
|
| Title | Number of Premature Infusion Set Changes |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Faster-acting Insulin Aspart | NovoRapid® |
|---|---|---|
| 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). |
| Measure Participants | 25 | 12 |
| Number [Episodes] |
21
|
4
|
Adverse Events
| 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® | ||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Faster-acting Insulin Aspart | NovoRapid® | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/25 (0%) | 0/12 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Faster-acting Insulin Aspart | NovoRapid® | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/25 (36%) | 6/12 (50%) | ||
| Eye disorders | ||||
| Diabetic retinopathy | 0/25 (0%) | 0 | 1/12 (8.3%) | 1 |
| General disorders | ||||
| Influenza like illness | 2/25 (8%) | 2 | 0/12 (0%) | 0 |
| Pyrexia | 1/25 (4%) | 1 | 1/12 (8.3%) | 1 |
| Infections and infestations | ||||
| Nasopharyngitis | 3/25 (12%) | 3 | 1/12 (8.3%) | 1 |
| Otitis media | 0/25 (0%) | 0 | 1/12 (8.3%) | 1 |
| Sinusitis | 0/25 (0%) | 0 | 1/12 (8.3%) | 1 |
| Tonsillitis | 0/25 (0%) | 0 | 1/12 (8.3%) | 1 |
| Upper respiratory tract infection | 0/25 (0%) | 0 | 1/12 (8.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 2/25 (8%) | 3 | 0/12 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 1/25 (4%) | 1 | 2/12 (16.7%) | 2 |
| Oropharyngeal pain | 0/25 (0%) | 0 | 2/12 (16.7%) | 2 |
| Sinus congestion | 0/25 (0%) | 0 | 1/12 (8.3%) | 1 |
| Upper respiratory tract congestion | 0/25 (0%) | 0 | 1/12 (8.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 0/25 (0%) | 0 | 1/12 (8.3%) | 1 |
| Rash | 0/25 (0%) | 0 | 1/12 (8.3%) | 1 |
Limitations/Caveats
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.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
"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
| Name/Title | Global Clinical Registry (GCR, 1452) |
|---|---|
| Organization | Novo Nordisk A/S |
| Phone | |
| clinicaltrials@novonordisk.com |
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01999322
Other Study ID Numbers:
- NN1218-3931
- 2013-002233-37
- U1111-1143-2316
First Posted:
Dec 3, 2013
Last Update Posted:
Oct 31, 2017
Last Verified:
Oct 1, 2017