Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Africa and Asia. The aim of the trial is to compare patient-adjusted versus physician-adjusted titration of BIAsp 30 combined with metformin in type 2 diabetes patients uncontrolled on NPH insulin.
Interventions
DRUGbiphasic insulin aspart 30
Dose individually adjusted by the subjects themselves according to the titration algorithm every second week. Administered subcutaneously (s.c., under the skin) twice daily.
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 12 months prior to screening * Currently treated with a NPH insulin for at least 3 months prior to screening * Stable treatment (no change in dose or regimen) with a total daily dose of at least 1500 mg metformin or maximum tolerated dose (minimum 1000 mg) ± additional OAD treatment. The metformin treatment must have been stable for at least 2 months prior to screening * HbA1c between 7.0% and 10.0% (both inclusive). (One re-test within one week of screening visit is allowed. The last sample will be conclusive.) * Body Mass Index (BMI) below or equal to 40.0 kg/m\^2 * Able and willing to eat at least 2 main meals each day during the trial * Able and willing to adhere to the protocol including compliance with performance of self measured plasma glucose (SMPG), injection regimen and titrating themselves according to the protocol * Experience in performing self-measured plasma glucose (SMPG)
Exclusion criteria
* Treatment with any thiazolidinedione (TZD) and Glucagon-like peptide-1 (GLP-1) receptor agonists or pramlintide within the last 3 months prior to screening * Impaired hepatic function defined as alanine aminotransferase (ALAT) above or equal to 2.5 times upper referenced limit. (One re-test within one week of screening visit is allowed. The last sample will be conclusive.) * Impaired kidney function with serum creatinine above or equal to 133 µmol/L (1.5 mg/dL) for males and above or equal to 124 µmol/L (1.4 mg/dL) for females. (One re-test within one week of screening visit is allowed. The last sample will be conclusive.) * Cardiac problems or uncontrolled treated/untreated severe hypertension (defined as systolic blood pressure above or equal to 180 mmHg and/or diastolic blood pressure above or equal to 100 mmHg) * Previous use of pre-mixed insulin products (pre-mixed insulin analogues or pre-mixed human preparations) * Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic episode, during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months * Known proliferative retinopathy or maculopathy requiring treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline | Week 0, week 20 | Change in HbA1c (%) from baseline to the end of the treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG) (Laboratory Values) From Baseline | Week 0, week 20 | Change in FPG (laboratory values) from baseline to the end of the treatment period |
| Number of Hypoglycaemic Episodes During the Trial From Baseline | Week 20 | The number of hypoglycaemic episodes (a blood glucose level of approximately 2.8 mmol/L \[50 mg/dL\] or plasma glucose level 3.1 mmol/L \[56 mg/dL\]) during the trial. |
| Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D) | Week 0, week 20 | Mean change from baseline in Treatment Related Impact Measure - Diabetes (TRIM-D) scores. The score measured treatment satisfaction which included an overall score as well the subscale scores (daily life, diabetes management, compliance and psychological health). The scores were transformed to a 0-100 scale with higher scores indicating a better health state. |
| Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D)-Treatment Burden | Week 0, week 20 | Mean change from baseline in Treatment Related Impact Measure - Diabetes (TRIM-D) scores. The score measured treatment satisfaction which included a subscale score -treatment burden. The scores were transformed to a 0-100 scale with higher scores indicating a better health state. |
Countries
Egypt, Indonesia, Morocco, Saudi Arabia, Tunisia, Vietnam
Participant flow
Recruitment details
The trial was conducted at 18 sites in 5 countries as follows: Egypt: 4 sites, Indonesia: 2 sites, Morocco: 4 sites, Saudi Arabia: 4 sites, Vietnam: 4 sites.
Pre-assignment details
The subjects continued on their previous NPH insulin and OADs upto randomisation (visit 2). At randomisation, the subjects discontinued these treatments except metformin.
Participants by arm
| Arm | Count |
|---|---|
| Subject-driven Titration The subjects received BIAsp 30. The treatment dose was individually adjusted by the subjects themselves according to the titration algorithm every second week. Trial product was administered subcutaneously (s.c., under the skin) twice daily. | 76 |
| Investigator-driven Titration The subjects received BIAsp 30. The treatment dose was adjusted according to the directions given by the investigator. Trial product was administered subcutaneously (s.c., under the skin) twice daily. | 79 |
| Total | 155 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Unclassified | 0 | 3 |
| Overall Study | Withdrawal criteria | 4 | 7 |
Baseline characteristics
| Characteristic | Subject-driven Titration | Investigator-driven Titration | Total |
|---|---|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 10.22 | 54.9 years STANDARD_DEVIATION 9.77 | 54.7 years STANDARD_DEVIATION 9.96 |
| Fasting plasma glucose (mg/dL) | 156.8 mg/dL STANDARD_DEVIATION 59.03 | 148.5 mg/dL STANDARD_DEVIATION 54.24 | 152.6 mg/dL STANDARD_DEVIATION 56.64 |
| HbA1c (%) | 8.5 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.88 | 8.7 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.78 | 8.6 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.83 |
| Sex: Female, Male Female | 60 Participants | 56 Participants | 116 Participants |
| Sex: Female, Male Male | 16 Participants | 23 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 76 | 23 / 78 |
| serious Total, serious adverse events | 0 / 76 | 5 / 78 |
Outcome results
Primary
Change in HbA1c From Baseline
Change in HbA1c (%) from baseline to the end of the treatment period.
Time frame: Week 0, week 20
Population: Full analysis set (FAS) included all randomised subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Subject-driven Titration | Change in HbA1c From Baseline | -1.27 percentage change in HbA1c | Standard Error 0.11 |
| Investigator-driven Titration | Change in HbA1c From Baseline | -1.04 percentage change in HbA1c | Standard Error 0.11 |
Comparison: The null-hypothesis was tested against the alternative hypothesis of non-inferiority as given by: H0: D \> 0.4% against HA: D ≤ 0.4% where D is the mean treatment difference for change in HbA1c (subject-driven titration minus investigator-driven titration).p-value: <0.00195% CI: [-0.54, 0.08]Regression, Linear
Secondary
Change in Fasting Plasma Glucose (FPG) (Laboratory Values) From Baseline
Change in FPG (laboratory values) from baseline to the end of the treatment period
Time frame: Week 0, week 20
Population: Full analysis set (FAS) included all randomised subjects. Missing data were imputed using last observation carried forward (LOCF). A total of 150 subjects contributed to the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subject-driven Titration | Change in Fasting Plasma Glucose (FPG) (Laboratory Values) From Baseline | -20.0 mg/dL | Standard Deviation 67.23 |
| Investigator-driven Titration | Change in Fasting Plasma Glucose (FPG) (Laboratory Values) From Baseline | -9.1 mg/dL | Standard Deviation 62.99 |
Secondary
Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D)
Mean change from baseline in Treatment Related Impact Measure - Diabetes (TRIM-D) scores. The score measured treatment satisfaction which included an overall score as well the subscale scores (daily life, diabetes management, compliance and psychological health). The scores were transformed to a 0-100 scale with higher scores indicating a better health state.
Time frame: Week 0, week 20
Population: Full analysis set (FAS) included all randomised subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subject-driven Titration | Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D) | Diabetes management | 12.7 scores on a scale | Standard Deviation 22.79 |
| Subject-driven Titration | Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D) | Psychological health | 8.4 scores on a scale | Standard Deviation 23.97 |
| Subject-driven Titration | Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D) | Compliance | 7.2 scores on a scale | Standard Deviation 27.69 |
| Subject-driven Titration | Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D) | Total score | 8.2 scores on a scale | Standard Deviation 16.52 |
| Subject-driven Titration | Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D) | Daily life | 1.9 scores on a scale | Standard Deviation 21.84 |
| Investigator-driven Titration | Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D) | Total score | 6.6 scores on a scale | Standard Deviation 15.14 |
| Investigator-driven Titration | Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D) | Daily life | 3.6 scores on a scale | Standard Deviation 20.04 |
| Investigator-driven Titration | Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D) | Diabetes management | 6.9 scores on a scale | Standard Deviation 22.77 |
| Investigator-driven Titration | Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D) | Compliance | 8.9 scores on a scale | Standard Deviation 19.54 |
| Investigator-driven Titration | Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D) | Psychological health | 6.1 scores on a scale | Standard Deviation 21.82 |
Secondary
Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D)-Treatment Burden
Mean change from baseline in Treatment Related Impact Measure - Diabetes (TRIM-D) scores. The score measured treatment satisfaction which included a subscale score -treatment burden. The scores were transformed to a 0-100 scale with higher scores indicating a better health state.
Time frame: Week 0, week 20
Population: Full analysis set (FAS) included all randomised subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subject-driven Titration | Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D)-Treatment Burden | 10.4 scores on a scale | Standard Deviation 21 |
| Investigator-driven Titration | Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D)-Treatment Burden | 8.0 scores on a scale | Standard Deviation 22.9 |
Secondary
Number of Hypoglycaemic Episodes During the Trial From Baseline
The number of hypoglycaemic episodes (a blood glucose level of approximately 2.8 mmol/L \[50 mg/dL\] or plasma glucose level 3.1 mmol/L \[56 mg/dL\]) during the trial.
Time frame: Week 20
Population: Full analysis set (FAS) included all randomised subjects. Missing data were imputed using last observation carried forward (LOCF). 154 subjects contributed to the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subject-driven Titration | Number of Hypoglycaemic Episodes During the Trial From Baseline | 167 episodes |
| Investigator-driven Titration | Number of Hypoglycaemic Episodes During the Trial From Baseline | 222 episodes |