Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Asia. The aim of this trial is to compare the glycaemic control when subjects initiate a biphasic insulin aspart 30 treatment followed by an intensified treatment if treatment target of HbA1c below 7% is not reached by OAD (oral anti-diabetic drugs) alone.
Interventions
DRUGbiphasic insulin aspart 30
Administered subcutaneously (under the skin) once daily, before breakfast. The trial has 3 treatment phases for both treatment arms
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with type 2 diabetes for a minimum of 6 months prior to Visit 1 * HbA1c at least 7.0 % - maximum 11 % at screening * Subject is insulin naïve (short-term insulin treatment of up to 14 days is allowed) * An antidiabetic regimen that has been stable for at least 3 months prior to screening * An antidiabetic regimen that includes a minimum of 2 OADs * OADs dosed at least 50% of the maximum recommended dose
Exclusion criteria
* Known or suspected hypersensitivity to trial product(s) or related products * Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice) * The receipt of any investigational medicinal product within one month prior to this trial * Suffer from a life threatening disease (cancer) * Cardiac disease: class III or IV congestive heart failure (CHF), unstable angina, and or any myocardial infarction (treated or untreated) within 6 months prior to screening * Hepatic insufficiency (Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) above 2 times the central laboratory's upper reference limit) * Renal insufficiency (serum creatinine above 1.6 mg/dl for males; 1.4 mg/dl for females * Recurrent hypoglycaemia or hypoglycaemic unawareness * Anemia (haemoglobin below 10 mg/dl)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 11 | Week 0, Week 11 | Estimated mean change from baseline in HbA1c after 11 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in FPG (Fasting Plasma Glucose) From Baseline to Week 36 | Week 0, Week 36 | Estimated mean change from baseline in FPG after 36 weeks of treatment |
| Number of Treatment Emergent Hypoglycaemic Episodes | Week 0 to Week 36 | A hypoglycaemic episode will be defined as treatment emergent if the onset of the episode is on or after the first day of trial product, and no later than the last day on trial product. |
Countries
Iran
Participant flow
Recruitment details
The trial was conducted at 5 sites in Iran
Pre-assignment details
Subjects were on a stable antidiabetic regimen which includes a minimum of 2 OADs, daily for at least 3 months prior to screening. OAD doses were at least 50 percent of the maximum recommended dose.
Participants by arm
| Arm | Count |
|---|---|
| Pre-breakfast BIAsp 30 Subjects were started on BIAsp 30 (a biphasic formulation of insulin aspart (IAsp) in which 30% is soluble and the remaining 70% is protaminized insulin aspart) subcutaneously once daily (OD) pre-breakfast. Then they were intensified to twice daily (BID) or thrice daily (TID) if glycaemic control is not achieved, within three 12 weeks of treatment phases by titrating according to SMBG levels. | 122 |
| Pre-dinner BIAsp 30 Subjects were started on BIAsp 30 (a biphasic formulation of insulin aspart (IAsp) in which 30% is soluble and the remaining 70% is protaminized insulin aspart) subcutaneously once daily (OD) pre-dinner. Then they were intensified to BID or TID if glycaemic control is not achieved, within three 12 weeks of treatment phases by titrating according to SMBG levels. | 123 |
| Total | 245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Unclassified | 5 | 5 |
| Overall Study | Withdrawal Criteria | 8 | 11 |
Baseline characteristics
| Characteristic | Pre-breakfast BIAsp 30 | Pre-dinner BIAsp 30 | Total |
|---|---|---|---|
| Age, Continuous | 55.6 years STANDARD_DEVIATION 9.32 | 54.8 years STANDARD_DEVIATION 10.32 | 55.2 years STANDARD_DEVIATION 9.82 |
| Fasting plasma glucose (FPG) | 192.7 mg/dL STANDARD_DEVIATION 68.56 | 199.3 mg/dL STANDARD_DEVIATION 63.8 | 196.0 mg/dL STANDARD_DEVIATION 66.16 |
| Glycosylated haemoglobin (HbA1c) | 9.1 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.07 | 9.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1 | 9.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.04 |
| Sex: Female, Male Female | 72 Participants | 74 Participants | 146 Participants |
| Sex: Female, Male Male | 50 Participants | 49 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 122 | 19 / 123 |
| serious Total, serious adverse events | 3 / 122 | 4 / 123 |
Outcome results
Primary
Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 11
Estimated mean change from baseline in HbA1c after 11 weeks of treatment
Time frame: Week 0, Week 11
Population: Full analysis set (FAS) includes all randomised subjects and missing data was imputed using baseline observation carried forward (BOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pre-breakfast BIAsp 30 | Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 11 | -1.04 percentage of glycosylated haemoglobin | Standard Error 0.1 |
| Pre-dinner BIAsp 30 | Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 11 | -0.90 percentage of glycosylated haemoglobin | Standard Error 0.1 |
Comparison: H0: D \> 0.4% against H1: D ≤ 0.4% where D is the mean treatment difference for change in HbA1c (pre-breakfast OD minus pre-dinner OD)p-value: <0.00195% CI: [-0.4, 0.13]Regression, Linear
Secondary
Change in FPG (Fasting Plasma Glucose) From Baseline to Week 36
Estimated mean change from baseline in FPG after 36 weeks of treatment
Time frame: Week 0, Week 36
Population: Full analysis set (FAS) includes all randomised subjects and missing data was imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pre-breakfast BIAsp 30 | Change in FPG (Fasting Plasma Glucose) From Baseline to Week 36 | -61.57 mg/dL | Standard Deviation 4.5 |
| Pre-dinner BIAsp 30 | Change in FPG (Fasting Plasma Glucose) From Baseline to Week 36 | -58.43 mg/dL | Standard Deviation 4.48 |
p-value: 0.621595% CI: [-15.65, 9.37]Regression, Linear
Secondary
Number of Treatment Emergent Hypoglycaemic Episodes
A hypoglycaemic episode will be defined as treatment emergent if the onset of the episode is on or after the first day of trial product, and no later than the last day on trial product.
Time frame: Week 0 to Week 36
Population: Safety analysis set includes all subjects who received at least one dose of the trial product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-breakfast BIAsp 30 | Number of Treatment Emergent Hypoglycaemic Episodes | 1181 episodes |
| Pre-dinner BIAsp 30 | Number of Treatment Emergent Hypoglycaemic Episodes | 953 episodes |