Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 diabetes mellitus, Japanese, phase 2, efficacy, safety, dapagliflozin
Brief summary
The purpose of this study is to obtain information on efficacy and safety of dapagliflozin in Japanese patients with Type 2 Diabetes. This will be done by comparing the effect of dapagliflozin to placebo when given in oral doses.
Interventions
DRUGDapagliflozin
once daily, 12 weeks
DRUGPlacebo
once daily, 12 weeks
Sponsors
Bristol-Myers Squibb
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Japanese Subjects with type 2 diabetes mellitus. * Strictly/relatively treatment naïve Subjects with HbA1c ≥ 7.0% and ≤ 10%, or Subjects treated with single or two (less than half of the approved maximal dose for each) oral anti-hyperglycaemic agent with HbA1c ≤ 8%. * Provision of informed consent.
Exclusion criteria
* Having clinically relevant medical history or concurrent disease such as cardiovascular disease, renal disease, retinopathy, hepatic disease and haematological disease. * The investigator(s) judged that the Subject should not participate in the study according to screening test or medical history.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change in HbA1c Levels | Baseline to Week 12 | The primary efficacy endpoint is the absolute change in HbA1c from baseline to Week 12 or the last post-baseline measurement prior to Week 12, if no Week 12 assessment is available. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change in Fasting Plasma Glucose | Baseline to Week 12 | Change in fasting plasma glucose from baseline to Week 12 or the last post-baseline measurement prior to Week 12, if no Week 12 assessment is available. |
| Proportion of Participants Achieving Glycemic Response Defined as HbA1c <7% | At Week 12 | Proportion of participants achieving therapeutic glycemic response defined as glycosylated hemoglobin \<7%, after 12 weeks of double-blind therapy |
Countries
Japan
Participant flow
Recruitment details
Enrollment: 417; randomized: 279 Study Start Date: August 2009 Study Completion Date: May 2010 Primary Completion Date: May 2010
Participants by arm
| Arm | Count |
|---|---|
| 1mg Dapagliflozin Dapagliflozin tablet 1 mg once daily | 59 |
| 2.5mg Dapagliflozin Dapagliflozin tablet 2.5 mg once daily | 56 |
| 5mg Dapagliflozin Dapagliflozin tablet 5 mg once daily | 58 |
| 10mg Dapagliflozin Dapagliflozin tablet 10 mg once daily | 52 |
| Placebo Placebo Comparator | 54 |
| Total | 279 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Incorrect Enrolment | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Safety | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Subject No Longer Meets Study Criteria | 2 | 2 | 0 | 0 | 5 |
| Overall Study | Various | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | 1mg Dapagliflozin | 2.5mg Dapagliflozin | 5mg Dapagliflozin | 10mg Dapagliflozin | Placebo | Total |
|---|---|---|---|---|---|---|
| Age Continuous | 55.9 years STANDARD_DEVIATION 9.73 | 57.7 years STANDARD_DEVIATION 9.33 | 58.0 years STANDARD_DEVIATION 9.5 | 56.5 years STANDARD_DEVIATION 11.47 | 58.4 years STANDARD_DEVIATION 9.97 | 57.3 years STANDARD_DEVIATION 9.98 |
| HBA1C | 8.10 percent STANDARD_DEVIATION 0.785 | 7.92 percent STANDARD_DEVIATION 0.74 | 8.05 percent STANDARD_DEVIATION 0.66 | 8.18 percent STANDARD_DEVIATION 0.69 | 8.12 percent STANDARD_DEVIATION 0.714 | 8.07 percent STANDARD_DEVIATION 0.72 |
| Race/Ethnicity, Customized Japanese | 59 Participants | 56 Participants | 58 Participants | 52 Participants | 54 Participants | 279 Participants |
| Sex: Female, Male Female | 12 Participants | 17 Participants | 11 Participants | 13 Participants | 11 Participants | 64 Participants |
| Sex: Female, Male Male | 47 Participants | 39 Participants | 47 Participants | 39 Participants | 43 Participants | 215 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 59 | 13 / 56 | 14 / 58 | 13 / 52 | 14 / 54 |
| serious Total, serious adverse events | 2 / 59 | 1 / 56 | 2 / 58 | 1 / 52 | 0 / 54 |
Outcome results
Primary
Adjusted Mean Change in HbA1c Levels
The primary efficacy endpoint is the absolute change in HbA1c from baseline to Week 12 or the last post-baseline measurement prior to Week 12, if no Week 12 assessment is available.
Time frame: Baseline to Week 12
Population: Full Analysis Set, participants with non-missing baseline and Week 12 (LOCF) values
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 1mg Dapagliflozin | Adjusted Mean Change in HbA1c Levels | -0.12 percent |
| 2.5mg Dapagliflozin | Adjusted Mean Change in HbA1c Levels | -0.10 percent |
| 5mg Dapagliflozin | Adjusted Mean Change in HbA1c Levels | -0.37 percent |
| 10mg Dapagliflozin | Adjusted Mean Change in HbA1c Levels | -0.44 percent |
| Placebo | Adjusted Mean Change in HbA1c Levels | 0.35 percent |
Comparison: The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.015 applying Dunnett's adjustment, two-sided)p-value: <0.000195% CI: [-0.67, -0.28]ANCOVA
Comparison: The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.015 applying Dunnett's adjustment, two-sided)p-value: <0.000195% CI: [-0.65, -0.26]ANCOVA
Comparison: The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.015 applying Dunnett's adjustment, two-sided)p-value: <0.000195% CI: [-0.92, -0.53]ANCOVA
Comparison: The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.015 applying Dunnett's adjustment, two-sided)p-value: <0.000195% CI: [-0.99, -0.59]ANCOVA
Secondary
Adjusted Mean Change in Fasting Plasma Glucose
Change in fasting plasma glucose from baseline to Week 12 or the last post-baseline measurement prior to Week 12, if no Week 12 assessment is available.
Time frame: Baseline to Week 12
Population: Full Analysis Set, participants with non-missing baseline and Week 12 (LOCF) values
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 1mg Dapagliflozin | Adjusted Mean Change in Fasting Plasma Glucose | -16.63 mg/dL |
| 2.5mg Dapagliflozin | Adjusted Mean Change in Fasting Plasma Glucose | -19.97 mg/dL |
| 5mg Dapagliflozin | Adjusted Mean Change in Fasting Plasma Glucose | -23.49 mg/dL |
| 10mg Dapagliflozin | Adjusted Mean Change in Fasting Plasma Glucose | -31.92 mg/dL |
| Placebo | Adjusted Mean Change in Fasting Plasma Glucose | 9.45 mg/dL |
Comparison: The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0p-value: <0.000195% CI: [-35.45, -16.7]ANCOVA
Comparison: The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0p-value: <0.000195% CI: [-38.7, -20.14]ANCOVA
Comparison: The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0p-value: <0.000195% CI: [-42.28, -23.6]ANCOVA
Comparison: The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0p-value: <0.000195% CI: [-50.9, -31.85]ANCOVA
Secondary
Proportion of Participants Achieving Glycemic Response Defined as HbA1c <7%
Proportion of participants achieving therapeutic glycemic response defined as glycosylated hemoglobin \<7%, after 12 weeks of double-blind therapy
Time frame: At Week 12
Population: Full Analysis Set, participants with non-missing baseline and week 12 (LOCF) values
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1mg Dapagliflozin | Proportion of Participants Achieving Glycemic Response Defined as HbA1c <7% | 1.7 Percentage of participants |
| 2.5mg Dapagliflozin | Proportion of Participants Achieving Glycemic Response Defined as HbA1c <7% | 9.3 Percentage of participants |
| 5mg Dapagliflozin | Proportion of Participants Achieving Glycemic Response Defined as HbA1c <7% | 5.2 Percentage of participants |
| 10mg Dapagliflozin | Proportion of Participants Achieving Glycemic Response Defined as HbA1c <7% | 9.6 Percentage of participants |
| Placebo | Proportion of Participants Achieving Glycemic Response Defined as HbA1c <7% | 1.9 Percentage of participants |
Comparison: H0: proportion(treat) minus proportion(placebo) = 0 versus HA: proportion(treat) minus proportion(placebo) =/= 0p-value: 195% CI: [-9.1, 7.6]Fisher Exact
Comparison: H0: proportion(treat) minus proportion(placebo) = 0 versus HA: proportion(treat) minus proportion(placebo) =/= 0p-value: 0.205795% CI: [-2.3, 18.8]Fisher Exact
Comparison: H0: proportion(treat) minus proportion(placebo) = 0 versus HA: proportion(treat) minus proportion(placebo) =/= 0p-value: 0.620395% CI: [-6.2, 13.2]Fisher Exact
Comparison: H0: proportion(treat) minus proportion(placebo) = 0 versus HA: proportion(treat) minus proportion(placebo) =/= 0p-value: 0.20595% CI: [-2, 19.5]Fisher Exact