Trial Outcomes & Findings for Comparison of the Blood Sugar Lowering Effect of Biphasic Insulin Aspart 30 and Insulin Glargine Both Combined With Metformin and Glimepiride in Chinese and Japanese Subjects With Type 2 Diabetes New to Insulin Treatment (NCT NCT01123980)
NCT ID: NCT01123980
Last Updated: 2017-02-24
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
521 participants
Primary outcome timeframe
Week 0, week 24
Results posted on
2017-02-24
Participant Flow
The trial was conducted at 35 sites in two countries: China (21 sites) and Japan (14 sites).
At the screening, eligible subjects entered the run-in period before being randomised. During the 3 week run-in period, subjects switched from insulin secretagogue to glimepiride. During the last 2 weeks, the total dose of glimepiride was kept at 4mg/day. Subjects continued their pre-trial metformin dose.
Participant milestones
| Measure |
BIAsp 30
0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Insulin Glargine
0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
|---|---|---|
|
Overall Study
STARTED
|
261
|
260
|
|
Overall Study
COMPLETED
|
242
|
236
|
|
Overall Study
NOT COMPLETED
|
19
|
24
|
Reasons for withdrawal
| Measure |
BIAsp 30
0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Insulin Glargine
0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
6
|
|
Overall Study
Protocol Violation
|
6
|
6
|
|
Overall Study
Withdrawal by Subject
|
5
|
3
|
|
Overall Study
Unclassified
|
6
|
7
|
Baseline Characteristics
Comparison of the Blood Sugar Lowering Effect of Biphasic Insulin Aspart 30 and Insulin Glargine Both Combined With Metformin and Glimepiride in Chinese and Japanese Subjects With Type 2 Diabetes New to Insulin Treatment
Baseline characteristics by cohort
| Measure |
BIAsp 30
n=261 Participants
0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Insulin Glargine
n=260 Participants
0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Total
n=521 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.6 years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
56.1 years
STANDARD_DEVIATION 9.9 • n=7 Participants
|
56.3 years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
|
Gender
Female
|
114 Participants
n=5 Participants
|
119 Participants
n=7 Participants
|
233 Participants
n=5 Participants
|
|
Gender
Male
|
147 Participants
n=5 Participants
|
141 Participants
n=7 Participants
|
288 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
261 Participants
n=5 Participants
|
260 Participants
n=7 Participants
|
521 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
China
|
210 participants
n=5 Participants
|
212 participants
n=7 Participants
|
422 participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
51 participants
n=5 Participants
|
48 participants
n=7 Participants
|
99 participants
n=5 Participants
|
|
Height
|
165.3 cm
STANDARD_DEVIATION 8.6 • n=5 Participants
|
165.2 cm
STANDARD_DEVIATION 8.2 • n=7 Participants
|
165.3 cm
STANDARD_DEVIATION 8.4 • n=5 Participants
|
|
Weight
|
70.0 kg
STANDARD_DEVIATION 11.6 • n=5 Participants
|
70.6 kg
STANDARD_DEVIATION 12.5 • n=7 Participants
|
70.3 kg
STANDARD_DEVIATION 12.1 • n=5 Participants
|
|
Body Mass Index (BMI)
|
25.53 kg/m^2
STANDARD_DEVIATION 3.39 • n=5 Participants
|
25.76 kg/m^2
STANDARD_DEVIATION 3.44 • n=7 Participants
|
25.65 kg/m^2
STANDARD_DEVIATION 3.41 • n=5 Participants
|
|
HbA1c (glycosylated haemoglobin) at randomisation
|
8.7 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.88 • n=5 Participants
|
8.14 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.86 • n=7 Participants
|
8.15 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.87 • n=5 Participants
|
|
Duration of diabetes
|
9.23 years
STANDARD_DEVIATION 7.15 • n=5 Participants
|
9.47 years
STANDARD_DEVIATION 6.61 • n=7 Participants
|
9.35 years
STANDARD_DEVIATION 6.88 • n=5 Participants
|
|
Diabetic complications at baseline
Yes
|
72 participants
n=5 Participants
|
75 participants
n=7 Participants
|
147 participants
n=5 Participants
|
|
Diabetic complications at baseline
No
|
189 participants
n=5 Participants
|
185 participants
n=7 Participants
|
374 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 0, week 24Population: Full analysis set using LOCF (last observation carried forward) consists of all randomised subjects who were exposed to at least one dose of trial product(s)
Outcome measures
| Measure |
BIAsp 30
n=261 Participants
0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Insulin Glargine
n=260 Participants
0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
|---|---|---|
|
Change in Glycosylated Haemoglobin (HbA1c)
|
-0.68 percentage of glycosylated haemoglobin
Standard Error 0.06
|
-0.56 percentage of glycosylated haemoglobin
Standard Error 0.06
|
SECONDARY outcome
Timeframe: Week 24Population: Full analysis set using LOCF (last observation carried forward) consists of all randomised subjects who were exposed to at least one dose of the trial product(s).
Glycaemic control measured by 9-point plasma glucose (SPMG) profiles. The 9 timepoints for self-measurement during the day were: before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, before bedtime, at 2-4 a.m. and before breakfast the following day.
Outcome measures
| Measure |
BIAsp 30
n=261 Participants
0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Insulin Glargine
n=260 Participants
0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
|---|---|---|
|
9-point Plasma Glucose Profiles
Before breakfast
|
6.46 mmol/L
Standard Error 0.09
|
6.49 mmol/L
Standard Error 0.09
|
|
9-point Plasma Glucose Profiles
2 hours after breakfast
|
10.18 mmol/L
Standard Error 0.19
|
10.11 mmol/L
Standard Error 0.19
|
|
9-point Plasma Glucose Profiles
Before lunch
|
7.35 mmol/L
Standard Error 0.17
|
7.22 mmol/L
Standard Error 0.17
|
|
9-point Plasma Glucose Profiles
2 hours after lunch
|
10.50 mmol/L
Standard Error 0.20
|
10.22 mmol/L
Standard Error 0.20
|
|
9-point Plasma Glucose Profiles
Before dinner
|
7.67 mmol/L
Standard Error 0.16
|
7.03 mmol/L
Standard Error 0.16
|
|
9-point Plasma Glucose Profiles
2 hours after dinner
|
9.36 mmol/L
Standard Error 0.19
|
10.88 mmol/L
Standard Error 0.19
|
|
9-point Plasma Glucose Profiles
Before bedtime
|
8.14 mmol/L
Standard Error 0.18
|
9.39 mmol/L
Standard Error 0.18
|
|
9-point Plasma Glucose Profiles
At 2-4 a.m.
|
6.58 mmol/L
Standard Error 0.13
|
7.06 mmol/L
Standard Error 0.13
|
|
9-point Plasma Glucose Profiles
Before breakfast the following day
|
6.51 mmol/L
Standard Error 0.10
|
6.35 mmol/L
Standard Error 0.10
|
SECONDARY outcome
Timeframe: Week 24Population: Full analysis set using LOCF (last observation carried forward) consists of all randomised subjects who were exposed to at least one dose of the trial product(s).
The percentage of subjects achieving the treatment target for glycosylated haemoglobin A1c after 24 weeks of treatment
Outcome measures
| Measure |
BIAsp 30
n=261 Participants
0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Insulin Glargine
n=260 Participants
0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
|---|---|---|
|
Percentage of Subjects Achieving HbA1c Below 7.0%
|
29.1 percentage (%) of subjects
|
30.0 percentage (%) of subjects
|
SECONDARY outcome
Timeframe: Week 24Population: Full analysis set using LOCF (last observation carried forward) consists of all randomised subjects who were exposed to at least one dose of the trial product(s).
The percentage of subjects achieving the treatment target for glycosylated haemoglobin A1c after 24 weeks of treatment
Outcome measures
| Measure |
BIAsp 30
n=261 Participants
0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Insulin Glargine
n=260 Participants
0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
|---|---|---|
|
Percentage of Subjects Achieving HbA1c Below or Equal to 6.5%
|
14.9 percentage (%) of subjects
|
14.2 percentage (%) of subjects
|
SECONDARY outcome
Timeframe: Weeks 0-24Population: The safety analysis set contains all subjects exposed to at least one dose of investigational product(s).
Outcome measures
| Measure |
BIAsp 30
n=261 Participants
0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Insulin Glargine
n=260 Participants
0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
|---|---|---|
|
Number of Hypoglycaemic Episodes - All
|
745 episodes
|
605 episodes
|
SECONDARY outcome
Timeframe: Weeks 0-24Population: The safety analysis set contains all subjects exposed to at least one dose of investigational product(s).
Hypoglycaemic episodes (hypos) summarised based on American Diabetes Association classification (severe, documented symptomatic, asymptomatic, probable symptomatic, and relative hypoglycaemia) and according to additional definition (minor hypoglycaemia). Severe hypos: requiring another person to actively administer resuscitative actions. Minor hypos: symptoms with plasma glucose below 3.1 mmol/L (56 mg/dl), or any asympomatic plasma glucose below 3.1 mmol/L.
Outcome measures
| Measure |
BIAsp 30
n=261 Participants
0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Insulin Glargine
n=260 Participants
0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
|---|---|---|
|
Number of Hypoglycaemic Episodes - Severe and Minor
Minor
|
154 episodes
|
125 episodes
|
|
Number of Hypoglycaemic Episodes - Severe and Minor
Severe
|
0 episodes
|
1 episodes
|
SECONDARY outcome
Timeframe: Weeks 0-24Population: The safety analysis set contains all subjects exposed to at least one dose of investigational product(s).
All episodes classified into nocturnal (time of onset between 00:00 (included) and 05:59 (included)).
Outcome measures
| Measure |
BIAsp 30
n=261 Participants
0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Insulin Glargine
n=260 Participants
0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
|---|---|---|
|
Number of Hypoglycaemic Episodes
|
97 episodes
|
63 episodes
|
Adverse Events
BIAsp 30
Serious events: 2 serious events
Other events: 26 other events
Deaths: 0 deaths
Insulin Glargine
Serious events: 5 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
BIAsp 30
n=261 participants at risk
0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Insulin Glargine
n=260 participants at risk
0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
|---|---|---|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/261 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
0.77%
2/260 • Number of events 2 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/261 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
0.38%
1/260 • Number of events 1 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adrenal adenoma
|
0.38%
1/261 • Number of events 1 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
0.00%
0/260 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma
|
0.00%
0/261 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
0.38%
1/260 • Number of events 1 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/261 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
0.38%
1/260 • Number of events 1 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
|
Nervous system disorders
Cerebral infarction
|
0.38%
1/261 • Number of events 1 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
0.00%
0/260 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
Other adverse events
| Measure |
BIAsp 30
n=261 participants at risk
0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
Insulin Glargine
n=260 participants at risk
0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
10.0%
26/261 • Number of events 31 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
10.8%
28/260 • Number of events 37 • The adverse events were collected in a timespan of 24 weeks.
The safety analysis set contains all subjects exposed to at least one dose of investigational products.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Novo Nordisk reserves the right not to release data until specified milestones. This includes the right not to release interim results from clinical trials. At the end of the trial, one or more manuscripts for publication will be prepared in collaboration between Investigator(s) and Novo Nordisk. Novo Nordisk will not suppress or veto publications; however Novo Nordisk reserves the right to postpone publication and/or communication for a short time to protect intellectual property.
- Publication restrictions are in place
Restriction type: OTHER