Trial Outcomes & Findings for Effect of Biphasic Insulin Aspart 30 Combined With Metformin on Blood Glucose Control in Subjects With Type 2 Diabetes Inadequately Controlled With Basal Insulin (NCT NCT00669864)
NCT ID: NCT00669864
Last Updated: 2016-04-01
Results Overview
Change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 16 weeks (end of treatment)
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
293 participants
Primary outcome timeframe
week 0, week 16
Results posted on
2016-04-01
Participant Flow
22 sites in China
Eligible subjects, treated with basal insulin, stopped their oral anti-diabetic drug treatment and started a run-in period of forced metformin titration. Subjects on current metformin therapy could go through a modified titration. Doses were up-titrated weekly until either the max tolerated dose of at least 1500mg/day or a max dose of 2000mg/day.
Participant milestones
| Measure |
BIAsp 30-30
Individual adjusted dose of biphasic insulin aspart 30 administered before breakfast and dinner in combination with metformin 1000-2000mg, up to three times daily
|
|---|---|
|
Overall Study
STARTED
|
293
|
|
Overall Study
COMPLETED
|
284
|
|
Overall Study
NOT COMPLETED
|
9
|
Reasons for withdrawal
| Measure |
BIAsp 30-30
Individual adjusted dose of biphasic insulin aspart 30 administered before breakfast and dinner in combination with metformin 1000-2000mg, up to three times daily
|
|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
Protocol Violation
|
2
|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Other
|
2
|
Baseline Characteristics
Effect of Biphasic Insulin Aspart 30 Combined With Metformin on Blood Glucose Control in Subjects With Type 2 Diabetes Inadequately Controlled With Basal Insulin
Baseline characteristics by cohort
| Measure |
BIAsp 30-30
n=293 Participants
Individual adjusted dose of biphasic insulin aspart 30 administered before breakfast and dinner in combination with metformin 1000-2000mg, up to three times daily
|
|---|---|
|
Age, Continuous
|
54 Years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
139 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
154 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
293 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Previous treatment
Basal insulin analogue
|
122 Participants
n=5 Participants
|
|
Previous treatment
Basal human insulin
|
169 Participants
n=5 Participants
|
|
Previous treatment
Animal insulin
|
2 Participants
n=5 Participants
|
|
BMI
|
24.89 kg/m^2
STANDARD_DEVIATION 3.28 • n=5 Participants
|
|
Duration of diabetes
|
8.54 Years
STANDARD_DEVIATION 5.49 • n=5 Participants
|
|
HbA1c
|
8.16 percentage (%) of total haemoglobin
STANDARD_DEVIATION 0.89 • n=5 Participants
|
|
Weight
|
68.1 kg
STANDARD_DEVIATION 12.2 • n=5 Participants
|
PRIMARY outcome
Timeframe: week 0, week 16Population: Intention-to-Treat analysis set (ITT) is all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
Change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 16 weeks (end of treatment)
Outcome measures
| Measure |
BIAsp 30-30
n=293 Participants
Individual adjusted dose of biphasic insulin aspart 30 administered before breakfast and dinner in combination with metformin 1000-2000mg, up to three times daily
|
|---|---|
|
Change in HbA1c (Glycosylated Haemoglobin A1c)
|
-1.303 percentage (%) of total haemoglobin
Standard Error 0.056
|
SECONDARY outcome
Timeframe: week 0, week 16Population: Intention-to-Treat analysis set (ITT) is all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
Summary of change in 8-point plasma glucose profile by week and time. The 8 time points measured were: Before each meal (breakfast, lunch and dinner), at 2 hours after each meal (breakfast, lunch and dinner), at bedtime, and at 3 AM, measured over 16 weeks of treatment
Outcome measures
| Measure |
BIAsp 30-30
n=293 Participants
Individual adjusted dose of biphasic insulin aspart 30 administered before breakfast and dinner in combination with metformin 1000-2000mg, up to three times daily
|
|---|---|
|
Change in 8-point Plasma Glucose Profile
Before breakfast, N=282
|
-1.95 mg/dL
Standard Error 0.15
|
|
Change in 8-point Plasma Glucose Profile
2 hours after breakfast, N=282
|
-3.69 mg/dL
Standard Error 0.25
|
|
Change in 8-point Plasma Glucose Profile
Before lunch, N=279
|
-2.60 mg/dL
Standard Error 0.22
|
|
Change in 8-point Plasma Glucose Profile
2 hours after lunch, N=282
|
-2.67 mg/dL
Standard Error 0.24
|
|
Change in 8-point Plasma Glucose Profile
Before dinner, N=282
|
-2.38 mg/dL
Standard Error 0.22
|
|
Change in 8-point Plasma Glucose Profile
2 hours after dinner, N=281
|
-3.63 mg/dL
Standard Error 0.27
|
|
Change in 8-point Plasma Glucose Profile
Bedtime, N=279
|
-3.10 mg/dL
Standard Error 0.24
|
|
Change in 8-point Plasma Glucose Profile
3 AM, N=279
|
-2.23 mg/dL
Standard Error 0.18
|
SECONDARY outcome
Timeframe: week 16Population: Intention-to-Treat analysis set (ITT) using LOCF (Last Observation Carried Forward) is all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
Percentage of subjects achieving the treatment target of a glycosylated haemoglobin A1c (HbA1c) level below 7.0% after 16 weeks of treatment
Outcome measures
| Measure |
BIAsp 30-30
n=293 Participants
Individual adjusted dose of biphasic insulin aspart 30 administered before breakfast and dinner in combination with metformin 1000-2000mg, up to three times daily
|
|---|---|
|
Percentage of Subjects Achieving HbA1c Less Than 7.0%
|
60.4 percentage of participants
|
SECONDARY outcome
Timeframe: week 16Population: Intention-to-Treat analysis set (ITT) using LOCF (Last Observation Carried Forward) is all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
Percentage of subjects achieving the treatment target of a glycosylated haemoglobin A1c (HbA1c) level below or equal to 6.5% after 16 weeks of treatment
Outcome measures
| Measure |
BIAsp 30-30
n=293 Participants
Individual adjusted dose of biphasic insulin aspart 30 administered before breakfast and dinner in combination with metformin 1000-2000mg, up to three times daily
|
|---|---|
|
Percentage of Subjects Achieving HbA1c Below or Equal to 6.5%
|
38.9 percentage of participants
|
SECONDARY outcome
Timeframe: weeks 0-16Population: Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
Total number of hypoglycaemic episodes experienced in the trial from week 0 (baseline) to week 16 (end of treatment). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L or 56 mg/dL. Symptoms only if subject was able to treat her/himself and with either no plasma glucose or blood glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L or 56 mg/dL.
Outcome measures
| Measure |
BIAsp 30-30
n=293 Participants
Individual adjusted dose of biphasic insulin aspart 30 administered before breakfast and dinner in combination with metformin 1000-2000mg, up to three times daily
|
|---|---|
|
Hypoglycaemic Episodes
Major
|
0 episodes
|
|
Hypoglycaemic Episodes
Minor
|
39 episodes
|
|
Hypoglycaemic Episodes
Symptoms only
|
203 episodes
|
SECONDARY outcome
Timeframe: weeks 0-16Population: Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
Total number of hypoglycaemic episodes experienced in the trial from week 0 (baseline) to week 16 (end of treatment) during the day (diurnal) and the night (nocturnal).
Outcome measures
| Measure |
BIAsp 30-30
n=293 Participants
Individual adjusted dose of biphasic insulin aspart 30 administered before breakfast and dinner in combination with metformin 1000-2000mg, up to three times daily
|
|---|---|
|
Hypoglycaemic Episodes, Diurnal/Nocturnal
Diurnal
|
188 episodes
|
|
Hypoglycaemic Episodes, Diurnal/Nocturnal
Nocturnal
|
34 episodes
|
|
Hypoglycaemic Episodes, Diurnal/Nocturnal
Start time missing
|
20 episodes
|
Adverse Events
BIAsp 30-30
Serious events: 0 serious events
Other events: 80 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
BIAsp 30-30
n=293 participants at risk
Individual adjusted dose of biphasic insulin aspart 30 administered before breakfast and dinner in combination with metformin 1000-2000mg, up to three times daily
|
|---|---|
|
Cardiac disorders
Coronary Artery Disease
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Eye disorders
Eye pain
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Eye disorders
Vision blurred
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.68%
2/293 • Number of events 2 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.68%
2/293 • Number of events 2 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Gastrointestinal disorders
Diarrhoea
|
1.4%
4/293 • Number of events 4 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Gastrointestinal disorders
Enteritis
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Gastrointestinal disorders
Gastric dilatation
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Gastrointestinal disorders
Nausea
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Gastrointestinal disorders
Periodontitis
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Gastrointestinal disorders
Toothache
|
2.0%
6/293 • Number of events 6 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Gastrointestinal disorders
Vomiting
|
1.4%
4/293 • Number of events 4 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
General disorders
Adverse drug reaction
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
General disorders
Feeling abnormal
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
General disorders
Oedema
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
General disorders
Pain
|
0.34%
1/293 • Number of events 2 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
2.0%
6/293 • Number of events 6 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Immune system disorders
Hypersensitivity
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Infections and infestations
Influenza
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Infections and infestations
Nasopharyngitis
|
5.1%
15/293 • Number of events 21 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Infections and infestations
Otitis externa
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Infections and infestations
Pharyngitis
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Infections and infestations
Pneumonia
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.68%
2/293 • Number of events 2 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Injury, poisoning and procedural complications
Animal bite
|
0.68%
2/293 • Number of events 2 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Injury, poisoning and procedural complications
Soft tissue injury
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Investigations
Alanine aminotransferase increased
|
1.0%
3/293 • Number of events 3 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Investigations
Blood triglycerides abnormal
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Investigations
Blood triglycerides increased
|
0.68%
2/293 • Number of events 2 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Investigations
Electrocardiogram ST segment depression
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Investigations
Electrocardiogram ST-T segment abnormal
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Investigations
Electrocardiogram T wave abnormal
|
0.68%
2/293 • Number of events 2 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Investigations
Lipids abnormal
|
1.0%
3/293 • Number of events 3 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Investigations
Lipids increased
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Investigations
Low density lipoprotein abnormal
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
4.8%
14/293 • Number of events 14 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
1.4%
4/293 • Number of events 4 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Metabolism and nutrition disorders
Lipid metabolism disorder
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Musculoskeletal and connective tissue disorders
Periarthritis
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Nervous system disorders
Convulsion
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Nervous system disorders
Dizziness
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Nervous system disorders
Vascular headache
|
0.34%
1/293 • Number of events 2 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Renal and urinary disorders
Renal failure
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.34%
1/293 • Number of events 1 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
|
Vascular disorders
Hypertension
|
0.68%
2/293 • Number of events 2 • The adverse events were collected in a time span of 16 weeks.
Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
|
Additional Information
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