Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Asia. This single arm trial aims to evaluate the blood glucose control with twice daily biphasic insulin aspart 30 in combination with metformin in Chinese subjects with type 2 diabetes inadequately controlled with once or twice daily basal insulin.
Interventions
DRUGbiphasic insulin aspart 30
Subcutaneous (under the skin) injection, twice daily
DRUGmetformin
Tablets, 1000 - 2000 mg daily
Sponsors
Novo Nordisk A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes * Currently treated with basal insulin once or twice daily with or without oral anti-diabetic drugs (OADs) for at least 3 months * HbA1c (glycosylated haemoglobin A1c) within the range of 7.5% to10.0% ( both inclusive) * BMI (Body Mass Index) maximum 40 kg/m2
Exclusion criteria
* Metformin contraindications according to local practice * Systemically treated with TZDs (thiazolidinediones) for more than one month within 6 months prior to this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c (Glycosylated Haemoglobin A1c) | week 0, week 16 | Change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 16 weeks (end of treatment) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 8-point Plasma Glucose Profile | week 0, week 16 | 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 |
| Percentage of Subjects Achieving HbA1c Less Than 7.0% | week 16 | Percentage of subjects achieving the treatment target of a glycosylated haemoglobin A1c (HbA1c) level below 7.0% after 16 weeks of treatment |
| Percentage of Subjects Achieving HbA1c Below or Equal to 6.5% | week 16 | 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 |
| Hypoglycaemic Episodes | weeks 0-16 | 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. |
| Hypoglycaemic Episodes, Diurnal/Nocturnal | weeks 0-16 | 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). |
Countries
China
Participant flow
Recruitment details
22 sites in China
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 293 |
| Total | 293 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other | 2 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | BIAsp 30-30 |
|---|---|
| Age, Continuous | 54 Years STANDARD_DEVIATION 9.6 |
| BMI | 24.89 kg/m^2 STANDARD_DEVIATION 3.28 |
| Duration of diabetes | 8.54 Years STANDARD_DEVIATION 5.49 |
| HbA1c | 8.16 percentage (%) of total haemoglobin STANDARD_DEVIATION 0.89 |
| Previous treatment Animal insulin | 2 Participants |
| Previous treatment Basal human insulin | 169 Participants |
| Previous treatment Basal insulin analogue | 122 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 293 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 139 Participants |
| Sex: Female, Male Male | 154 Participants |
| Weight | 68.1 kg STANDARD_DEVIATION 12.2 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 80 / 293 |
| serious Total, serious adverse events | 0 / 293 |
Outcome results
Primary
Change in HbA1c (Glycosylated Haemoglobin A1c)
Change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 16 weeks (end of treatment)
Time frame: week 0, week 16
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIAsp 30-30 | Change in HbA1c (Glycosylated Haemoglobin A1c) | -1.303 percentage (%) of total haemoglobin | Standard Error 0.056 |
Comparison: The null hypothesis (H0): HbA1c after 16 weeks - HbA1c at baseline ≥ 0% against the alternative hypothesis (H1): HbA1c after 16 weeks - HbA1c at baseline \< 0%. If H0 rejected at a significance level of 2.5%, declare a significant mean HbA1c decreasep-value: <0.000195% CI: [-1.414, -1.192]t-test, 1 sided
Secondary
Change in 8-point Plasma Glucose Profile
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
Time frame: week 0, week 16
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIAsp 30-30 | Change in 8-point Plasma Glucose Profile | Before breakfast, N=282 | -1.95 mg/dL | Standard Error 0.15 |
| BIAsp 30-30 | Change in 8-point Plasma Glucose Profile | 2 hours after breakfast, N=282 | -3.69 mg/dL | Standard Error 0.25 |
| BIAsp 30-30 | Change in 8-point Plasma Glucose Profile | Before lunch, N=279 | -2.60 mg/dL | Standard Error 0.22 |
| BIAsp 30-30 | Change in 8-point Plasma Glucose Profile | 2 hours after lunch, N=282 | -2.67 mg/dL | Standard Error 0.24 |
| BIAsp 30-30 | Change in 8-point Plasma Glucose Profile | Before dinner, N=282 | -2.38 mg/dL | Standard Error 0.22 |
| BIAsp 30-30 | Change in 8-point Plasma Glucose Profile | 2 hours after dinner, N=281 | -3.63 mg/dL | Standard Error 0.27 |
| BIAsp 30-30 | Change in 8-point Plasma Glucose Profile | Bedtime, N=279 | -3.10 mg/dL | Standard Error 0.24 |
| BIAsp 30-30 | Change in 8-point Plasma Glucose Profile | 3 AM, N=279 | -2.23 mg/dL | Standard Error 0.18 |
Secondary
Hypoglycaemic Episodes
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.
Time frame: weeks 0-16
Population: Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIAsp 30-30 | Hypoglycaemic Episodes | Major | 0 episodes |
| BIAsp 30-30 | Hypoglycaemic Episodes | Minor | 39 episodes |
| BIAsp 30-30 | Hypoglycaemic Episodes | Symptoms only | 203 episodes |
Secondary
Hypoglycaemic Episodes, Diurnal/Nocturnal
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).
Time frame: weeks 0-16
Population: Safety analysis set consists of all subjects who entered the trial treatment period and exposed to at least one dose of trial product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIAsp 30-30 | Hypoglycaemic Episodes, Diurnal/Nocturnal | Diurnal | 188 episodes |
| BIAsp 30-30 | Hypoglycaemic Episodes, Diurnal/Nocturnal | Nocturnal | 34 episodes |
| BIAsp 30-30 | Hypoglycaemic Episodes, Diurnal/Nocturnal | Start time missing | 20 episodes |
Secondary
Percentage of Subjects Achieving HbA1c Below or Equal to 6.5%
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
Time frame: week 16
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIAsp 30-30 | Percentage of Subjects Achieving HbA1c Below or Equal to 6.5% | 38.9 percentage of participants |
Secondary
Percentage of Subjects Achieving HbA1c Less Than 7.0%
Percentage of subjects achieving the treatment target of a glycosylated haemoglobin A1c (HbA1c) level below 7.0% after 16 weeks of treatment
Time frame: week 16
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIAsp 30-30 | Percentage of Subjects Achieving HbA1c Less Than 7.0% | 60.4 percentage of participants |