High Blood Sugar, Type2 Diabetes
Conditions
Keywords
Phase3, Clinical trial, Type 2 Diabetes Mellitus
Brief summary
This is a long term, single arm, open label study to evaluate the safety and efficacy of dapagliflozin as monotherapy or in combination therapy with other anti diabetic drug in Japanese subjects with type 2 diabetes mellitus who have inadequate blood sugar control on diet and exercise or on other anti-diabetic treatment will be included in this study.
Interventions
DRUGDapagliflozin
Oral Dose 5 or 10 mg
Sponsors
Bristol-Myers Squibb
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent prior to any study specific procedures * Men or women age ≥20 years old (Either gender needs to be 40% or higher of total number of treated subjects) * diagnosed with type2 DM ; ≥6.5% and ≤10% at 1 week before treatment started
Exclusion criteria
* Type 1 diabetes mellitus, * FPG \>240 mg/dL before treatment started * Subjects who have history of unstable or rapidly progressing renal disease * Subjects who have severe hepatic insufficiency and/or significant abnormal liver function * Significant cardiovascular history
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Seated Systolic Blood Pressure | Baseline to Week 52 | To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood pressure |
| Mean Change in Seated Heart Rate | Baseline to Week 52 | To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in pulse |
| Mean Change in Seated Diastolic Blood Pressure | Baseline to Week 52 | To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood pressure |
| Proportion of Participants With Adverse Events | Long-term treatment up to 52 weeks | To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to adverse events |
| Proportion of Participants With Serious Adverse Events | Long-term treatment up to 52 weeks | To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to serious adverse events |
| Proportion of Participants With At Least One Episode of Hypoglycemia | Long-term treatment up to 52 weeks | To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to occurrence of hypoglycemia |
| Mean Change in Hematocrit | Baseline to Week 52 | To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in hematocrit |
| Mean Change in Alanine Aminotransferase (ALT) | Baseline to Week 52 | To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in alanine aminotransferase |
| Mean Change in Aspartate Aminotransferase (AST) | Baseline to Week 52 | To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in aspartate aminotransferase |
| Mean Change in Blood Urea Nitrogen (BUN) | Baseline to Week 52 | To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood urea nitrogen |
| Mean Change in Magnesium | Baseline to Week 52 | To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in magnesium (1 mEq/L equivalent to 0.50 mmol/L) |
| Mean Change in Serum Uric Acid | Baseline to Week 52 | To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in serum uric acid |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Body Weight | Baseline to Week 52 | To evaluate the efficacy of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in body weight |
| Mean Change in HbA1c Levels | Baseline to Week 52 | To evaluate the efficacy of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in HbA1c |
Countries
Japan
Participant flow
Recruitment details
First subject enrolled: 28-Feb-2011; Last subject last visit: 15-Sep-2012; 1030 participants were enrolled in 56 Japanese centers. 728 Japanese men and women aged \>=20 years with inadequate glycemic control (HbA1c levels of 6.5% to 10.0% prior to study treatment) with diet and exercise were treated.
Pre-assignment details
A 6-week wash-out period was applicable only for subjects with ongoing anti-diabetic treatment at enrolment. A 4-week lead-in period was applicable for all subjects.
Participants by arm
| Arm | Count |
|---|---|
| Monotherapy Dapagliflozin 5/10 mg only | 249 |
| All Combination Therapies Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs | 479 |
| Total | 728 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 17 |
| Overall Study | poor/non-compliance | 2 | 5 |
| Overall Study | subject no longer meets study criteria | 5 | 20 |
| Overall Study | Withdrawal by Subject | 11 | 28 |
Baseline characteristics
| Characteristic | Monotherapy | All Combination Therapies | Total |
|---|---|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 10.4 | 57.2 years STANDARD_DEVIATION 10.06 | 57.5 years STANDARD_DEVIATION 10.18 |
| Age, Customized 65 - <75 years | 55 participants | 102 participants | 157 participants |
| Age, Customized < 65 years | 182 participants | 365 participants | 547 participants |
| Age, Customized >= 75 years | 12 participants | 12 participants | 24 participants |
| Body Mass Index | 25.72 kg/m^2 STANDARD_DEVIATION 4.196 | 25.61 kg/m^2 STANDARD_DEVIATION 4.44 | 25.64 kg/m^2 STANDARD_DEVIATION 4.355 |
| Body Weight | 67.77 kg STANDARD_DEVIATION 13.437 | 67.40 kg STANDARD_DEVIATION 14.529 | 67.52 kg STANDARD_DEVIATION 14.157 |
| Fasting Plasma Glucose (FPG) | 140.29 mg/dL STANDARD_DEVIATION 25.355 | 147.35 mg/dL STANDARD_DEVIATION 29.097 | 144.93 mg/dL STANDARD_DEVIATION 28.057 |
| HbA1c | 7.53 Percent STANDARD_DEVIATION 0.761 | 7.82 Percent STANDARD_DEVIATION 0.865 | 7.72 Percent STANDARD_DEVIATION 0.842 |
| Region of Enrollment Japan | 249 participants | 479 participants | 728 participants |
| Seated Systolic Blood Pressure | 127.5 mmHg STANDARD_DEVIATION 13.73 | 125.8 mmHg STANDARD_DEVIATION 14.13 | 126.4 mmHg STANDARD_DEVIATION 14.01 |
| Sex: Female, Male Female | 103 Participants | 211 Participants | 314 Participants |
| Sex: Female, Male Male | 146 Participants | 268 Participants | 414 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 71 / 249 | 126 / 479 |
| serious Total, serious adverse events | 14 / 249 | 15 / 479 |
Outcome results
Primary
Mean Change in Alanine Aminotransferase (ALT)
To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in alanine aminotransferase
Time frame: Baseline to Week 52
Population: Safety Analysis Set, participants with non-missing baseline and week 52 values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean Change in Alanine Aminotransferase (ALT) | -7.1 U/L | Standard Error 0.955 |
| All Combination Therapies | Mean Change in Alanine Aminotransferase (ALT) | -5.4 U/L | Standard Error 0.622 |
Primary
Mean Change in Aspartate Aminotransferase (AST)
To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in aspartate aminotransferase
Time frame: Baseline to Week 52
Population: Safety Analysis Set, participants with non-missing baseline and week 52 values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean Change in Aspartate Aminotransferase (AST) | -3.9 U/L | Standard Error 0.695 |
| All Combination Therapies | Mean Change in Aspartate Aminotransferase (AST) | -2.6 U/L | Standard Error 0.41 |
Primary
Mean Change in Blood Urea Nitrogen (BUN)
To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood urea nitrogen
Time frame: Baseline to Week 52
Population: Safety Analysis Set, participants with non-missing baseline and week 52 values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean Change in Blood Urea Nitrogen (BUN) | 2.4 mg/dL | Standard Error 0.25 |
| All Combination Therapies | Mean Change in Blood Urea Nitrogen (BUN) | 2.3 mg/dL | Standard Error 0.168 |
Primary
Mean Change in Hematocrit
To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in hematocrit
Time frame: Baseline to Week 52
Population: Safety Analysis Set, participants with non-missing baseline and week 52 values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean Change in Hematocrit | 2.17 Percent | Standard Error 0.1396 |
| All Combination Therapies | Mean Change in Hematocrit | 2.00 Percent | Standard Error 0.1115 |
Primary
Mean Change in Magnesium
To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in magnesium (1 mEq/L equivalent to 0.50 mmol/L)
Time frame: Baseline to Week 52
Population: Safety Analysis Set, participants with non-missing baseline and week 52 values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean Change in Magnesium | 0.05 mEq/L | Standard Error 0.0074 |
| All Combination Therapies | Mean Change in Magnesium | 0.05 mEq/L | Standard Error 0.0064 |
Primary
Mean Change in Seated Diastolic Blood Pressure
To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood pressure
Time frame: Baseline to Week 52
Population: Safety Analysis Set, participants with non-missing baseline and week 52 values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean Change in Seated Diastolic Blood Pressure | -2.9 mmHg | Standard Deviation 8.16 |
| All Combination Therapies | Mean Change in Seated Diastolic Blood Pressure | -2.1 mmHg | Standard Deviation 8.73 |
Primary
Mean Change in Seated Heart Rate
To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in pulse
Time frame: Baseline to Week 52
Population: Safety Analysis Set, participants with non-missing baseline and week 52 values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean Change in Seated Heart Rate | -0.4 beats per minute (bpm) | Standard Deviation 7.52 |
| All Combination Therapies | Mean Change in Seated Heart Rate | 0.2 beats per minute (bpm) | Standard Deviation 7.95 |
Primary
Mean Change in Seated Systolic Blood Pressure
To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood pressure
Time frame: Baseline to Week 52
Population: Safety Analysis Set, participants with non-missing baseline and week 52 values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean Change in Seated Systolic Blood Pressure | -5.2 mmHg | Standard Deviation 11.68 |
| All Combination Therapies | Mean Change in Seated Systolic Blood Pressure | -3.9 mmHg | Standard Deviation 13.03 |
Primary
Mean Change in Serum Uric Acid
To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in serum uric acid
Time frame: Baseline to Week 52
Population: Safety Analysis Set, participants with non-missing baseline and week 52 values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean Change in Serum Uric Acid | -0.61 mg/dL | Standard Error 0.0578 |
| All Combination Therapies | Mean Change in Serum Uric Acid | -0.50 mg/dL | Standard Error 0.0374 |
Primary
Proportion of Participants With Adverse Events
To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to adverse events
Time frame: Long-term treatment up to 52 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Proportion of Participants With Adverse Events | 79.1 Percentage of participants |
| All Combination Therapies | Proportion of Participants With Adverse Events | 72.4 Percentage of participants |
Primary
Proportion of Participants With At Least One Episode of Hypoglycemia
To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to occurrence of hypoglycemia
Time frame: Long-term treatment up to 52 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Proportion of Participants With At Least One Episode of Hypoglycemia | 2.4 Percentage of participants |
| All Combination Therapies | Proportion of Participants With At Least One Episode of Hypoglycemia | 4.0 Percentage of participants |
Primary
Proportion of Participants With Serious Adverse Events
To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to serious adverse events
Time frame: Long-term treatment up to 52 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Proportion of Participants With Serious Adverse Events | 5.6 Percentage of participants |
| All Combination Therapies | Proportion of Participants With Serious Adverse Events | 3.1 Percentage of participants |
Other Pre-specified
Mean Change in Body Weight
To evaluate the efficacy of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in body weight
Time frame: Baseline to Week 52
Population: Full Analysis Set, participants with non-missing baseline and week 52 (LOCF) value
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean Change in Body Weight | -2.58 kg | 95% Confidence Interval 11.68 |
| All Combination Therapies | Mean Change in Body Weight | -2.06 kg | 95% Confidence Interval 13.03 |
Other Pre-specified
Mean Change in HbA1c Levels
To evaluate the efficacy of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in HbA1c
Time frame: Baseline to Week 52
Population: Full Analysis Set, participants with non-missing baseline and week 52 (LOCF) value
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean Change in HbA1c Levels | -0.66 Percent | 95% Confidence Interval 11.68 |
| All Combination Therapies | Mean Change in HbA1c Levels | -0.68 Percent | 95% Confidence Interval 13.03 |