Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Asia. The aim of the trial is to compare the glycaemic control of Levemir® (insulin detemir) administered once daily according to two titration algorithms after 20 weeks in subjects with type 2 diabetes inadequately controlled on metformin treatment with or without other anti-diabetic drugs (OADs).
Interventions
DRUGinsulin detemir
Insulin detemir was administered once daily to the subjects. The dose was titrated based on the previous breakfast SMPG values.
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 mellitus at least 3 months prior to Visit 1 (week -2) * \- Treatment with at least 1000 mg metformin per day with/without other OADs at a stable dose (at either the maximal tolerated dose or at least half of the maximum recommended dose according to the package insert) for at least 3 months prior to Visit 1 * \- Insulin-naïve subjects * \- HbA1c above or equal to 7.5% by central laboratory analysis * \- Body mass index (BMI) below or equal to 35.0 kg/m\^2
Exclusion criteria
* \- Female who is breast-feeding * \- The receipt of any investigational product within 4 weeks prior to Visit 1 * \- Any contraindication to insulin detemir according to the domestic labelling * \- Anticipated change of dose of any systemic treatment with products, which in the investigator's opinion could interfere with glucose metabolism (such as systemic corticosteroids, beta-blockers, monoamine oxidase \[MAO\] inhibitors) * \- Clinically significant diseases which, in the investigator's opinion, may confound the results of the trial or pose additional risk in administering trial product * \- Any conditions that the investigator judges would interfere with trial participation or evaluation of the results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycosylated Haemoglobin A1c (HbA1c) From Baseline. | Week 0, week 20 | Change in glycosylated haemoglobin A1c (HbA1c) (%) from baseline after 20 weeks of treatment. Only the subjects in the full analysis set with HbA1c values after 20 weeks of treatment were included. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | Week 20 | A treatment emergent adverse event (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than the day of visit 22.(week 20) |
| Change in HbA1c | Week 0, week 12 | Change in HbA1c at 12 weeks of treatment from visit 2. |
| Proportion of Subjects Achieving HbA1c Below 7.0% | Week 20 | Responder was a dichotomous endpoint (responder/non-responder) that was defined based on whether a subject had met the ADA HbA1c target at end of trial (HbA1c \< 7.0% at end of trial) during 20 weeks of treatment. |
| Change in Fasting Plasma Glucose From Baseline | week 0, week 12 | Change in fasting plasma glucose from baseline. |
| Incidence of Hypoglycaemic Episodes : Nocturnal (23:00-05:59) and Over 24 Hours. | For 20 weeks of treatment and over 24 hours | A hypoglycaemic episode was defined as treatment emergent if the onset of the episode occurred after the first administration of the investigational medicinal product (IMP), and no later than the last day on trial product. Hypoglycaemic episodes were defined as nocturnal if the time of onset was between 23:00 and 05:59 inclusive. All plasma glucose values: · equal or below 3.9 mmol/L (70 mg/dL) or · higher than 3.9 mmol/L (70 mg/dL) when they occur in conjunction with hypoglycaemic symptoms. |
Countries
South Korea
Participant flow
Recruitment details
The trial was conducted at 6 sites in 1 country: South Korea
Participants by arm
| Arm | Count |
|---|---|
| Insulin Detemir (3-0-3 Algorithm ) A once daily dosage of Insulin detemir (Levemir®) 100 U/mL 3 mL FlexPen® for subcutaneous administration was selected for this trial.During the treatment period insulin detemir was adjusted by the subject themselves (self-titration). Self-titration was performed every 3 days based on the lowest of three previous consecutive pre-breakfast SMPG values.Based on this glucose value, self-adjustment of insulin detemir dose was done. Metformin and Sulfonlylurea were allowed as OADs. For SMPG values , the following insulin detemir dose adjustments were done : \>6.1 mmol/L (\>110 mg/dL) +3U insulin detemir, 4.4-6.1 mmol/L (80-100 mg/dL) No adjustment in insulin detemir, \< 4.4 mmol/L (\<80 mg/dL) -3U insulin detemir. | 23 |
| Insulin Detemir (2-4-6-8 Algorithm ) A once daily dosage of Insulin detemir (Levemir®) 100 U/mL 3 mL FlexPen® for subcutaneous administration was selected for this trial.During the treatment period insulin detemir was adjusted by the subject themselves (self-titration). Self-titration was performed every 3 days based on the lowest of three previous consecutive pre-breakfast SMPG values.Based on this glucose value, self-adjustment of insulin detemir dose was done. Metformin and Sulfonlylurea were allowed as OADs. For SMPG values , the following insulin detemir dose adjustments were done : \>10.0 mmol/L (180 mg/dL) +8U insulin detemir, 9.1-10.0 mmol/L (163-180 mg/dL) +6U insulin detemir, 8.1-9.0 mmol/L (145-162 mg/dL) +4 U insulin detemir, 7.1-8.0 mmol/L (127-144 mg/dL) +2U insulin detemir, 6.1-7.0 mmol/L (109-126 mg/dL) +2U insulin detemir, 4.1-6.0 mmol/L (73-108 mg/dL) No adjustment in insulin detemir, 3.1-4.0 mmol/L (56-72 mg/dL) -2U insulin detemir, \<3.1 mmol/L (\<56 mg/dL) -4U insulin detemir. | 23 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Unclassified | 0 | 1 |
Baseline characteristics
| Characteristic | Insulin Detemir (3-0-3 Algorithm ) | Insulin Detemir (2-4-6-8 Algorithm ) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 4 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 19 Participants | 36 Participants |
| Gender Female | 14 Participants | 11 Participants | 25 Participants |
| Gender Male | 9 Participants | 12 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 23 | 5 / 23 |
| serious Total, serious adverse events | 0 / 23 | 1 / 23 |
Outcome results
Primary
Change in Glycosylated Haemoglobin A1c (HbA1c) From Baseline.
Change in glycosylated haemoglobin A1c (HbA1c) (%) from baseline after 20 weeks of treatment. Only the subjects in the full analysis set with HbA1c values after 20 weeks of treatment were included.
Time frame: Week 0, week 20
Population: Full analysis set (FAS) - included all randomised subjects. 2 subjects withdrew after randomisation in the detemir (2-4-6-8 algorithm) arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Detemir (3-0-3 Algorithm ) | Change in Glycosylated Haemoglobin A1c (HbA1c) From Baseline. | -0.9 Percent (%) glycosylated haemoglobin | Standard Deviation 1.3 |
| Insulin Detemir (2-4-6-8 Algorithm ) | Change in Glycosylated Haemoglobin A1c (HbA1c) From Baseline. | -1.0 Percent (%) glycosylated haemoglobin | Standard Deviation 1.2 |
Secondary
Change in Fasting Plasma Glucose From Baseline
Change in fasting plasma glucose from baseline.
Time frame: week 0, week 12
Population: Full analysis set (FAS) - included all randomised subjects.2 subjects withdrew after randomisation in the detemir (2-4-6-8 algorithm) arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Detemir (3-0-3 Algorithm ) | Change in Fasting Plasma Glucose From Baseline | -74.3 mg/dL | Standard Deviation 73 |
| Insulin Detemir (2-4-6-8 Algorithm ) | Change in Fasting Plasma Glucose From Baseline | -44.6 mg/dL | Standard Deviation 88.8 |
Secondary
Change in Fasting Plasma Glucose From Baseline
Change in fasting plasma glucose from baseline.
Time frame: Week 0, week 20
Population: Full analysis set (FAS) - included all randomised subjects.2 subjects withdrew after randomisation in the detemir (2-4-6-8 algorithm) arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Detemir (3-0-3 Algorithm ) | Change in Fasting Plasma Glucose From Baseline | -60.4 mg/dL | Standard Deviation 71.5 |
| Insulin Detemir (2-4-6-8 Algorithm ) | Change in Fasting Plasma Glucose From Baseline | -70.0 mg/dL | Standard Deviation 63.8 |
Secondary
Change in HbA1c
Change in HbA1c at 12 weeks of treatment from visit 2.
Time frame: Week 0, week 12
Population: Full analysis set (FAS) - included all randomised subjects. 2 subjects withdrew after randomisation in the detemir (2-4-6-8)algorithm arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Detemir (3-0-3 Algorithm ) | Change in HbA1c | -0.8 Percent (%) glycosylated haemoglobin | Standard Deviation 1.3 |
| Insulin Detemir (2-4-6-8 Algorithm ) | Change in HbA1c | -0.9 Percent (%) glycosylated haemoglobin | Standard Deviation 1.2 |
Secondary
Incidence of Adverse Events
A treatment emergent adverse event (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than the day of visit 22.(week 20)
Time frame: Week 20
Population: Safety analysis set - included all subjects receiving at least one dose of the trial product. Subjects in the safety set contributed to the evaluation as treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Detemir (3-0-3 Algorithm ) | Incidence of Adverse Events | Non Serious Adverse Events (NSAEs) | 24 events |
| Insulin Detemir (3-0-3 Algorithm ) | Incidence of Adverse Events | Treatment Emergent Adverse Events (TEAEs) | 24 events |
| Insulin Detemir (3-0-3 Algorithm ) | Incidence of Adverse Events | Serious Adverse Events (SAEs) | 0 events |
| Insulin Detemir (2-4-6-8 Algorithm ) | Incidence of Adverse Events | Serious Adverse Events (SAEs) | 1 events |
| Insulin Detemir (2-4-6-8 Algorithm ) | Incidence of Adverse Events | Non Serious Adverse Events (NSAEs) | 28 events |
| Insulin Detemir (2-4-6-8 Algorithm ) | Incidence of Adverse Events | Treatment Emergent Adverse Events (TEAEs) | 29 events |
Secondary
Incidence of Hypoglycaemic Episodes : Nocturnal (23:00-05:59) and Over 24 Hours.
A hypoglycaemic episode was defined as treatment emergent if the onset of the episode occurred after the first administration of the investigational medicinal product (IMP), and no later than the last day on trial product. Hypoglycaemic episodes were defined as nocturnal if the time of onset was between 23:00 and 05:59 inclusive. All plasma glucose values: · equal or below 3.9 mmol/L (70 mg/dL) or · higher than 3.9 mmol/L (70 mg/dL) when they occur in conjunction with hypoglycaemic symptoms.
Time frame: For 20 weeks of treatment and over 24 hours
Population: Safety Analysis Set (SAS): Included all subjects receiving at least one dose of trial product. Subjects contributed to the evaluation as treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Detemir (3-0-3 Algorithm ) | Incidence of Hypoglycaemic Episodes : Nocturnal (23:00-05:59) and Over 24 Hours. | Hypoglycaemic episodes | 72 Episodes |
| Insulin Detemir (3-0-3 Algorithm ) | Incidence of Hypoglycaemic Episodes : Nocturnal (23:00-05:59) and Over 24 Hours. | Nocturnal hypoglycaemic episodes | 22 Episodes |
| Insulin Detemir (2-4-6-8 Algorithm ) | Incidence of Hypoglycaemic Episodes : Nocturnal (23:00-05:59) and Over 24 Hours. | Hypoglycaemic episodes | 119 Episodes |
| Insulin Detemir (2-4-6-8 Algorithm ) | Incidence of Hypoglycaemic Episodes : Nocturnal (23:00-05:59) and Over 24 Hours. | Nocturnal hypoglycaemic episodes | 17 Episodes |
Secondary
Proportion of Subjects Achieving HbA1c Below 7.0%
Responder was a dichotomous endpoint (responder/non-responder) that was defined based on whether a subject had met the ADA HbA1c target at end of trial (HbA1c \< 7.0% at end of trial) during 20 weeks of treatment.
Time frame: Week 20
Population: Full analysis set (FAS) - included all randomised subjects. 2 subjects withdrew after randomisation in the detemir (2-4-6-8 algorithm ) arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Detemir (3-0-3 Algorithm ) | Proportion of Subjects Achieving HbA1c Below 7.0% | week 20 (Yes) | 8.7 percentage (%) of subjects |
| Insulin Detemir (3-0-3 Algorithm ) | Proportion of Subjects Achieving HbA1c Below 7.0% | week 20 (No) | 91.3 percentage (%) of subjects |
| Insulin Detemir (2-4-6-8 Algorithm ) | Proportion of Subjects Achieving HbA1c Below 7.0% | week 20 (Yes) | 14.3 percentage (%) of subjects |
| Insulin Detemir (2-4-6-8 Algorithm ) | Proportion of Subjects Achieving HbA1c Below 7.0% | week 20 (No) | 85.7 percentage (%) of subjects |