Trial Outcomes & Findings for Comparison of NN5401 Versus Biphasic Insulin Aspart 30 on a Twice Daily Regimen in Subjects With Type 2 Diabetes Mellitus (NCT NCT00842361)

NCT ID: NCT00842361

Last Updated: 2017-02-09

Results Overview

Rate of major and minor hypoglycaemic episodes per patient year (1year=365.25days) of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose ≤ 55 mg/dL.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

66 participants

Primary outcome timeframe

Week 0 to Week 6 + 5 days follow up

Results posted on

2017-02-09

Participant Flow

A total of 8 sites in Japan

Participant milestones

Participant milestones
Measure
SIAC
Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted
Mix30
Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted.
Overall Study
STARTED
33
33
Overall Study
Exposed
33
32
Overall Study
COMPLETED
32
31
Overall Study
NOT COMPLETED
1
2

Reasons for withdrawal

Reasons for withdrawal
Measure
SIAC
Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted
Mix30
Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted.
Overall Study
Protocol Violation
1
0
Overall Study
Unclassified
0
2

Baseline Characteristics

Comparison of NN5401 Versus Biphasic Insulin Aspart 30 on a Twice Daily Regimen in Subjects With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
SIAC
n=33 Participants
Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted
Mix30
n=32 Participants
Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted.
Total
n=65 Participants
Total of all reporting groups
Age, Continuous
64.3 years
STANDARD_DEVIATION 8.4 • n=5 Participants
64.7 years
STANDARD_DEVIATION 11.2 • n=7 Participants
64.5 years
STANDARD_DEVIATION 9.8 • n=5 Participants
Gender
Female
9 Participants
n=5 Participants
14 Participants
n=7 Participants
23 Participants
n=5 Participants
Gender
Male
24 Participants
n=5 Participants
18 Participants
n=7 Participants
42 Participants
n=5 Participants
Glycosylated haemoglobin (HbA1c)
7.36 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.86 • n=5 Participants
7.44 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.84 • n=7 Participants
7.40 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.84 • n=5 Participants
Fasting plasma glucose (FPG)
144.6 mg/L
STANDARD_DEVIATION 36.4 • n=5 Participants
140.8 mg/L
STANDARD_DEVIATION 38.6 • n=7 Participants
142.7 mg/L
STANDARD_DEVIATION 37.3 • n=5 Participants
Body weight
61.22 kg
STANDARD_DEVIATION 9.88 • n=5 Participants
57.32 kg
STANDARD_DEVIATION 7.94 • n=7 Participants
59.30 kg
STANDARD_DEVIATION 9.12 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0 to Week 6 + 5 days follow up

Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.

Rate of major and minor hypoglycaemic episodes per patient year (1year=365.25days) of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose ≤ 55 mg/dL.

Outcome measures

Outcome measures
Measure
SIAC
n=33 Participants
Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted
Mix30
n=32 Participants
Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted.
Rate of Major and Minor Hypoglycaemic Episodes
Major
0 Episodes /year of patient exposure
0 Episodes /year of patient exposure
Rate of Major and Minor Hypoglycaemic Episodes
Minor
13.63 Episodes /year of patient exposure
21.83 Episodes /year of patient exposure

PRIMARY outcome

Timeframe: Week 0 to Week 6 + 5 days follow up

Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.

Rate of nocturnal major and minor hypoglycaemic episodes per patient year (1year=365.25days) of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose ≤ 55 mg/dL. Episodes were defined as nocturnal if the time of onset was between 23:00 and 05:59 (both inclusive).

Outcome measures

Outcome measures
Measure
SIAC
n=33 Participants
Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted
Mix30
n=32 Participants
Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted.
Rate of Nocturnal Major and Minor Hypoglycaemic Episodes
Major
0 Episodes /year of patient exposure
0 Episodes /year of patient exposure
Rate of Nocturnal Major and Minor Hypoglycaemic Episodes
Minor
0.99 Episodes /year of patient exposure
2.03 Episodes /year of patient exposure

SECONDARY outcome

Timeframe: Week 0 to Week 6 + 5 days follow up

Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.

Corresponds to number of adverse events. Severity assessed by investigator. Mild: no or transient symptoms, no interference with subject's daily activities. Moderate: marked symptoms, moderate interference with subject's daily activities. Severe: considerable interference with subject's daily activities, unacceptable. Serious AE: AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure
SIAC
n=33 Participants
Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted
Mix30
n=32 Participants
Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted.
Number of Treatment Emergent Adverse Events (AEs)
Adverse events (AEs)
13 events
8 events
Number of Treatment Emergent Adverse Events (AEs)
Serious AEs
1 events
0 events
Number of Treatment Emergent Adverse Events (AEs)
Severe AEs
0 events
0 events
Number of Treatment Emergent Adverse Events (AEs)
Moderate AEs
1 events
0 events
Number of Treatment Emergent Adverse Events (AEs)
Mild AEs
12 events
8 events

SECONDARY outcome

Timeframe: Week 0, Week 6

Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator. Missing data is imputed using last observation carried forward (LOCF).

Change from baseline in body weight after 6 weeks of treatment

Outcome measures

Outcome measures
Measure
SIAC
n=33 Participants
Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted
Mix30
n=32 Participants
Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted.
Change in Body Weight
0.09 kg
Standard Deviation 0.79
-0.10 kg
Standard Deviation 0.99

SECONDARY outcome

Timeframe: Week 0, Week 6

Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator. Missing data is imputed using last observation carried forward (LOCF).

The number of subjects having an electrocardiogram (ECG) that changed from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant'. 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management.

Outcome measures

Outcome measures
Measure
SIAC
n=33 Participants
Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted
Mix30
n=32 Participants
Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted.
Electrocardiogram (ECG) Worsening
2 participants
0 participants

SECONDARY outcome

Timeframe: Week 0, Week 6

Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator. Missing data is imputed using last observation carried forward (LOCF).

Values at baseline (Week 0) and at Week 6

Outcome measures

Outcome measures
Measure
SIAC
n=33 Participants
Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted
Mix30
n=32 Participants
Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted.
Diastolic BP (Blood Pressure)
Week 6
76.8 mmHg
Standard Deviation 10.4
76.7 mmHg
Standard Deviation 10.0
Diastolic BP (Blood Pressure)
Week 0 (Baseline)
77.3 mmHg
Standard Deviation 11.1
75.4 mmHg
Standard Deviation 11.1

SECONDARY outcome

Timeframe: Week 0, Week 6.

Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator. Missing data is imputed using last observation carried forward (LOCF).

Values at baseline (Week 0) and at Week 6

Outcome measures

Outcome measures
Measure
SIAC
n=33 Participants
Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted
Mix30
n=32 Participants
Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted.
Systolic BP (Blood Pressure)
Week 0 (Baseline)
137.5 mmHg
Standard Deviation 15.5
130.8 mmHg
Standard Deviation 17.4
Systolic BP (Blood Pressure)
Week 6
137.0 mmHg
Standard Deviation 17.0
130.9 mmHg
Standard Deviation 16.0

Adverse Events

SIAC

Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths

Mix30

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
SIAC
n=33 participants at risk
Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted
Mix30
n=32 participants at risk
Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted.
Injury, poisoning and procedural complications
Thermal burn
3.0%
1/33 • Number of events 1 • The adverse events were collected in a time frame of 6 weeks + 5 days follow up.
The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
0.00%
0/32 • The adverse events were collected in a time frame of 6 weeks + 5 days follow up.
The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.

Other adverse events

Other adverse events
Measure
SIAC
n=33 participants at risk
Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted
Mix30
n=32 participants at risk
Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted.
Cardiac disorders
Supraventricular extrasystoles
6.1%
2/33 • Number of events 2 • The adverse events were collected in a time frame of 6 weeks + 5 days follow up.
The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
0.00%
0/32 • The adverse events were collected in a time frame of 6 weeks + 5 days follow up.
The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations
Nasopharyngitis
9.1%
3/33 • Number of events 3 • The adverse events were collected in a time frame of 6 weeks + 5 days follow up.
The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
9.4%
3/32 • Number of events 3 • The adverse events were collected in a time frame of 6 weeks + 5 days follow up.
The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Results disclosure agreements

  • Principal investigator is a sponsor employee Novo Nordisk maintains the right to be informed of any Investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Any such communication must be submitted in writing to the Novo Nordisk trial manager prior to submission for comments. Comments will be given within four weeks from receipt of the planned communication.
  • Publication restrictions are in place

Restriction type: OTHER