Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Asia. The aim of this clinical trial is to investigate the blood glucose lowering effect and the safety profile of repaglinide given alone compared to gliclazide given alone in Chinese subjects with type 2 diabetes who never have been treated with oral anti-diabetic drugs (OADs). This study also investigates the augment effect of repaglinide on the phases of insulin secretion as a subgroup study.
Interventions
DRUGrepaglinide
Individually adjusted dose for 16 weeks
DRUGgliclazide
Individually adjusted dose for 16 weeks
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes * Oral anti-diabetic drug (OAD) naïve (unsystematic OAD treatment 6 months prior to this trial is allowed) * Insulin naïve (less than 1 week of daily use of insulin therapy before trial start is allowed) * Lipid-lowing agent naïve * HbA1c: 6.5-8.5% * Fasting glucose: 6.1-13.0 mmol/L (110-234 mg/dl) * Body Mass Index (BMI): 20-35 kg/m\^2 * Be able and willing to perform self-monitored plasma glucose (SMPG) * Be able and willing to eat 3 main meals per day * Only applicable to subjects who will participate in the subgroup study: Be able and willing to perform and complete IVGTT (intravenous glucose tolerance test) at additional visits
Exclusion criteria
* Known or suspected allergy to repaglinide, gliclazide, or related products (for example sulfonamide or other sulphonylureas (SUs)), or any of the excipients in the study drugs * Previous participation in this study * Participation in a study of another investigational drug within 1 month prior to study start
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Glycosylated Haemoglobin (HbA1c) | Week 0, week 16 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 2-hour Postprandial Plasma Glucose (PPG) Over a Standard Meal | Week 0, week 16 | A standard meal contains 100g carbohydrate |
| Percentage of Participants Achieving the Treatment Target of HbA1c Below or Equal to 6.5% | Week 16 | — |
| Change in Fasting Serum Free Fatty Acid (FFA) From Baseline | Week 0, week 16 | — |
| Change in 2-hour Postprandial Serum Free Fatty Acid (FFA) Over a Standard Meal | Week 0, week 16 | — |
| Change in Fasting Plasma Glucose | Week 0, week 16 | — |
| Change in AUC0-180 of Plasma Glucose Concentration of IVGTT | Over the course of three hours at Week 0 and Week 16 | — |
| Number of All Treatment Emergent Hypoglycaemic Episodes | Weeks 0-16 | A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of trial product and no later than the last day of the trial product. |
| Cholesterol | Week 0, week 16 | The number of participants having a change in cholesterol from normal to abnormal. Abnormal means a value of blood cholesterol is out of the normal range. |
| Change in Body Weight | Week 0, week 16 | — |
| Change in AUC0-180 of Serum Insulin Concentration of IVGTT (Intravenous Glucose Tolerance Test) | Over the course of three hours at Week 0 and Week 16 | — |
Countries
China
Participant flow
Recruitment details
The trial was conducted at 23 sites in China.
Pre-assignment details
Between screening and treatment with trial drug the participants were assessed for eligibility and were randomised to one of two treatment arms. A sub-group of 69 participants was recruited for intravenous glucose tolerance test and randomised into the repaglinide treatment group (35 participants) and gliclazide treatment group (34 participants)
Participants by arm
| Arm | Count |
|---|---|
| Repaglinide 1 mg repaglinide twice daily (weeks 0-4), titrated (individually adjusted) to maintenance dose (weeks 4-16). Maximum dose is 4 mg three times daily | 217 |
| Gliclazide 80 mg gliclazide once daily (weeks 0-4), titrated (individually adjusted) to maintenance dose (weeks 4-16). Maximum dose is 160 mg twice daily | 218 |
| Total | 435 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Protocol Violation | 7 | 6 |
| Overall Study | Unclassified | 12 | 20 |
Baseline characteristics
| Characteristic | Gliclazide | Repaglinide | Total |
|---|---|---|---|
| Age, Continuous | 53.5 years STANDARD_DEVIATION 9.9 | 54.1 years STANDARD_DEVIATION 10 | 53.8 years STANDARD_DEVIATION 9.9 |
| Body Mass Index (BMI) | 25.37 kg/m^2 STANDARD_DEVIATION 3.01 | 25.69 kg/m^2 STANDARD_DEVIATION 3 | 25.53 kg/m^2 STANDARD_DEVIATION 3 |
| Duration of diagnosed diabetes | 0.79 years STANDARD_DEVIATION 1.82 | 1.02 years STANDARD_DEVIATION 1.95 | 0.91 years STANDARD_DEVIATION 1.89 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 218 Participants | 217 Participants | 435 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 163.9 cm STANDARD_DEVIATION 8.4 | 163.2 cm STANDARD_DEVIATION 8.9 | 163.5 cm STANDARD_DEVIATION 8.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 218 Participants | 217 Participants | 435 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 218 participants | 217 participants | 435 participants |
| Sex: Female, Male Female | 95 Participants | 107 Participants | 202 Participants |
| Sex: Female, Male Male | 123 Participants | 110 Participants | 233 Participants |
| Weight | 68.4 kg STANDARD_DEVIATION 11.2 | 68.7 kg STANDARD_DEVIATION 11.6 | 68.6 kg STANDARD_DEVIATION 11.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 216 | 0 / 219 |
| serious Total, serious adverse events | 3 / 216 | 0 / 219 |
Outcome results
Primary
Change in Glycosylated Haemoglobin (HbA1c)
Time frame: Week 0, week 16
Population: Full analysis set (FAS) is randomised participants exposed to at least one dose of trial product after randomisation. Missing values were replaced with the last post-baseline data based on LOCF (last observation carried forward).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Repaglinide | Change in Glycosylated Haemoglobin (HbA1c) | -0.857 percentage (%) of total haemoglobin | Standard Error 0.051 |
| Gliclazide | Change in Glycosylated Haemoglobin (HbA1c) | -0.871 percentage (%) of total haemoglobin | Standard Error 0.051 |
Comparison: H0: Change from baseline in HbA1c of repaglinide therapy at 16 weeks of treatment - change from baseline in HbA1c of gliclazide therapy at 16 weeks of treatment \>= 0.4%. H1: Change from baseline in HbA1c of repaglinide therapy at 16 weeks of treatment - change from baseline in HbA1c of gliclazide therapy at 16 weeks of treatment \< 0.4%. Sample size was calculated to achieve a power of at least 85%, assuming an equal change in HbA1c and a common standard deviation of 1.2%.95% CI: [-0.115, 0.143]ANCOVA
Secondary
Change in 2-hour Postprandial Plasma Glucose (PPG) Over a Standard Meal
A standard meal contains 100g carbohydrate
Time frame: Week 0, week 16
Population: Full analysis set (FAS) is randomised participants exposed to at least one dose of trial product after randomisation. Missing values were replaced with the last post-baseline data based on LOCF (last observation carried forward).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Repaglinide | Change in 2-hour Postprandial Plasma Glucose (PPG) Over a Standard Meal | -0.596 mmol/L | Standard Error 0.215 |
| Gliclazide | Change in 2-hour Postprandial Plasma Glucose (PPG) Over a Standard Meal | -0.699 mmol/L | Standard Error 0.211 |
Secondary
Change in 2-hour Postprandial Serum Free Fatty Acid (FFA) Over a Standard Meal
Time frame: Week 0, week 16
Population: Full analysis set (FAS) is randomised participants exposed to at least one dose of trial product after randomisation. Missing values were replaced with the last post-baseline data based on LOCF (last observation carried forward).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Repaglinide | Change in 2-hour Postprandial Serum Free Fatty Acid (FFA) Over a Standard Meal | -0.003 mmol/L | Standard Error 0.007 |
| Gliclazide | Change in 2-hour Postprandial Serum Free Fatty Acid (FFA) Over a Standard Meal | -0.004 mmol/L | Standard Error 0.007 |
Secondary
Change in AUC0-180 of Plasma Glucose Concentration of IVGTT
Time frame: Over the course of three hours at Week 0 and Week 16
Population: A total of 69 participants were recruited into IVGTT, and were randomised into repaglinide treatment group (35 participants) and gliclazide treatment group (34 participants). Participants with eligible IVGTT profiles were included in IVGTT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Repaglinide | Change in AUC0-180 of Plasma Glucose Concentration of IVGTT | -272.30 min*mmol/L | Standard Deviation 290.79 |
| Gliclazide | Change in AUC0-180 of Plasma Glucose Concentration of IVGTT | -348.03 min*mmol/L | Standard Deviation 258.86 |
Secondary
Change in AUC0-180 of Serum Insulin Concentration of IVGTT (Intravenous Glucose Tolerance Test)
Time frame: Over the course of three hours at Week 0 and Week 16
Population: A total of 69 participants were recruited into IVGTT, and were randomised into repaglinide treatment group (35 participants) and gliclazide treatment group (34 participants). Participants with eligible IVGTT profiles were included in IVGTT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Repaglinide | Change in AUC0-180 of Serum Insulin Concentration of IVGTT (Intravenous Glucose Tolerance Test) | 5139.55 min*pmol/L | Standard Deviation 8720.8 |
| Gliclazide | Change in AUC0-180 of Serum Insulin Concentration of IVGTT (Intravenous Glucose Tolerance Test) | 1426.21 min*pmol/L | Standard Deviation 5262.15 |
Secondary
Change in Body Weight
Time frame: Week 0, week 16
Population: Full analysis set (FAS) is randomised participants exposed to at least one dose of trial product after randomisation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Repaglinide | Change in Body Weight | -0.750 kg | Standard Error 0.218 |
| Gliclazide | Change in Body Weight | -0.511 kg | Standard Error 0.215 |
Secondary
Change in Fasting Plasma Glucose
Time frame: Week 0, week 16
Population: Full analysis set (FAS) is randomised participants exposed to at least one dose of trial product after randomisation. Missing values were replaced with the last post-baseline data based on LOCF (last observation carried forward).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Repaglinide | Change in Fasting Plasma Glucose | -1.409 mmol/L | Standard Error 0.104 |
| Gliclazide | Change in Fasting Plasma Glucose | -1.667 mmol/L | Standard Error 0.102 |
Secondary
Change in Fasting Serum Free Fatty Acid (FFA) From Baseline
Time frame: Week 0, week 16
Population: Full analysis set (FAS) is randomised participants exposed to at least one dose of trial product after randomisation. Missing values were replaced with the last post-baseline data based on LOCF (last observation carried forward).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Repaglinide | Change in Fasting Serum Free Fatty Acid (FFA) From Baseline | -0.012 mmol/L | Standard Error 0.014 |
| Gliclazide | Change in Fasting Serum Free Fatty Acid (FFA) From Baseline | -0.02 mmol/L | Standard Error 0.014 |
Secondary
Cholesterol
The number of participants having a change in cholesterol from normal to abnormal. Abnormal means a value of blood cholesterol is out of the normal range.
Time frame: Week 0, week 16
Population: Safety analysis set contains all randomised participants exposed to at least one dose of trial drug(s)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Repaglinide | Cholesterol | 18 participants |
| Gliclazide | Cholesterol | 11 participants |
Secondary
Number of All Treatment Emergent Hypoglycaemic Episodes
A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of trial product and no later than the last day of the trial product.
Time frame: Weeks 0-16
Population: Safety analysis set contains all randomised participants exposed to at least one dose of trial drug(s). One participant was randomised into repaglinide group, but was dispensed gliclazide from the very beginning of the study due to the investigator's negligence. This participant continued the gliclazide treatment until the end of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Repaglinide | Number of All Treatment Emergent Hypoglycaemic Episodes | 165 episodes |
| Gliclazide | Number of All Treatment Emergent Hypoglycaemic Episodes | 147 episodes |
Secondary
Percentage of Participants Achieving the Treatment Target of HbA1c Below or Equal to 6.5%
Time frame: Week 16
Population: Full analysis set (FAS) is randomised participants exposed to at least one dose of trial product after randomisation. Missing values were replaced with the last post-baseline data based on LOCF (last observation carried forward).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Repaglinide | Percentage of Participants Achieving the Treatment Target of HbA1c Below or Equal to 6.5% | 62 percentage of participants |
| Gliclazide | Percentage of Participants Achieving the Treatment Target of HbA1c Below or Equal to 6.5% | 59 percentage of participants |