Diabetes Mellitus, Type 2, Kidney Function Tests
Conditions
Brief summary
The purpose of this study is to evaluate how dapagliflozin mechanism of action is impacted by Type 2 Diabetes Mellitus status and kidney function
Interventions
DRUGDapagliflozin
The study consists of a 2-week, open label, dapagliflozin (10mg) treatment period.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Provision of signed and dated, written informed consent prior to any study specific procedures * Female and/or male aged between 18 years and ≤80 years * In the diabetic arms - a diagnosis of T2DM with HbA1c ≥6.5% (≥48 mmol/mol) and \<10% (\<86 mmol/mol); and eGFR (CKD-EPI) between ≥25 and ≤50 mL/min/1.73m2 or between \>90 and ≤130 mL/min/1.73m2 for patients aged 59 years or younger, between \>85 and ≤130 mL/min/1.73m2 for patients aged 60 to 69 years, and between \>75 and ≤130 mL/min/1.73m2 for patients aged 70 years or older at the Screening Visit (Visit 1) * In the non-diabetic arm, HbA1c \<6.5% (\<48 mmol/mol) and an eGFR (CKD-EPI) between ≥25 and ≤50 mL/min/1.73m2 at the Screening Visit (Visit 1) * Patient specific optimal antihypertensive dose of an angiotensin receptor blocker at least 6 weeks before study treatment * In the diabetic arm (Group 2) an appropriate stable dose of metformin, or sulphonylurea, or metformin+sulphonylurea as anti-diabetic therapy for the last 12 weeks before study treatment * Stable urinary sodium excretion on 2 successive 24-hr urinary sodium excretion measurements. * In the diabetic arm with impaired renal function (Group 1), a stable insulin dosing (intermediate, long-acting, premixed insulin, basal bolus insulin) for the last 12 weeks prior to Visit 4 (Day 1), as judged by the Investigator. Metformin or sulphonylurea, or metformin+sulphonylurea together with insulin would be accepted, but is not mandatory. If used, stable dose of metformin or sulphonylurea, or metformin+sulphonylurea as anti-diabetic therapy for the last 12 weeks prior to Visit 4 (Day 1) is required.
Exclusion criteria
* Diagnosis of Type 1 Diabetes Mellitus * Any of the following cardiovascular/vascular diseases within 3 months prior to signing the consent; myocardial infarction, cardiac surgery or revascularization, unstable angina, unstable heart failure, heart failure NYHA Class IV, transient ischemic attack or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia * Symptoms/complaints suggestive of established neurogenic bladder and/or incomplete bladder emptying * History of bladder cancer, diagnosis of polycystic kidney disease, history or current lupus nephritis or unstable or rapidly progressing renal disease * UACR \>1000 mg/g at screening * Current/chronic use of the following medications: any anti-diabetic medication with the exception of metformin, sulphonylurea, angiotensin converting enzyme inhibitors, insulin (insulin only allowed in Group 1), oral glucocorticoids, non-steroidal anti-inflammatory drugs, immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants and monoamine oxidase inhibitors * Receiving immunosuppressive or other immunotherapy for primary or secondary renal disease within 6 months prior to screening * Current treatment or treatment within the last 2 weeks prior to screening with diuretics including loop diuretics, thiazides, and mineralocorticoid antagonists
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24-hour Sodium Excretion From Baseline to Start of Treatment | From baseline (Day -3 to Day -1) to start of treatment (Day 2 to Day 4) | Change in 24-hour sodium excretion during dapagliflozin treatment between baseline and average of Days 2 to 4 within each study group in patients with T2DM with preserved kidney function and in non-diabetics with impaired kidney function was assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24-hour Glucose Excretion From Baseline to Start of Treatment | From baseline (Day -3 to Day -1) to start of treatment (Day 2 to 4) | Average change in 24-hour glucose excretion from average baseline values to average start of treatment values (Day 2 to 4). |
| Change in 24-hour Glucose Excretion From Baseline to End of Treatment | From baseline (Day -3 to Day -1) to end of treatment (Day 12 to 14) | Average change in 24-hour glucose excretion from average baseline values to average end of treatment values (Day 12 to 14) |
| Change in 24-hour Glucose Excretion From End of Treatment to Follow-up | From end of treatment (Day 12 to 14) to follow-up (Day 15 to 17) | Average change in 24-hour glucose excretion from average end of treatment values (Day 12 to 14) to average values during follow-up (Day 15 to 17). |
| Change in Mean 24-hour Systolic Blood Pressure From Baseline to Start of Treatment | From baseline (Day -1) to start of treatment (Day 4) | Change in mean 24-hour systolic blood pressure from baseline to start of treatment (Day 4) |
| Change in Mean 24-hour Systolic Blood Pressure From Baseline to End of Treatment | From baseline (Day -1) to end of treatment (Day 13) | Change in mean 24-hour systolic blood pressure from baseline to end of treatment (Day 13). |
| Change in Mean 24-hour Systolic Blood Pressure From End of Treatment to End of Follow-up | From end of treatment (Day 13) to end of follow-up (Day 18) | Change in mean 24-hour systolic blood pressure from end of treatment (Day 13) to end of follow-up (Day 18). |
| Change in Plasma Volume From Baseline to Start of Treatment | From baseline (Day 1) to start of treatment (Day 4) | Change in plasma volume from baseline to start of treatment (Day 4). |
| Change in 24-hour Sodium Excretion From Baseline to End of Treatment and From End of Treatment to Follow-up | From baseline (Day -3 to Day -1) to end of treatment (Day 12 to 14); and from end of treatment (Day 12 to 14) to follow-up (Day 15 to 17) | Average change in 24-hour sodium excretion from average baseline values to average end of treatment values (Day 12 to 14); and from average end of treatment values (Day 12 to 14) to average values during follow-up (Day 15 to 17). |
| Change in Plasma Volume From End of Treatment to End of Follow-up | From end of treatment (Day 14) to end of follow-up (Day 18) | Change in plasma volume from end of treatment (Day 14) to end of follow-up (Day 18). |
| Change in Extracellular Volume From Baseline to Start of Treatment | From baseline (Day 1) to start of treatment (Day 4) | Change in extracellular volume from baseline to start of treatment (Day 4). |
| Change in Extracellular Volume From Baseline to End of Treatment | From baseline (Day 1) to end of treatment (Day 14) | Change in extracellular volume from baseline to end of treatment (Day 14). |
| Change in Extracellular Volume From End of Treatment to End of Follow-up | From end of treatment (Day 14) to end of follow-up (Day 18) | Change in extracellular volume from end of treatment (Day 14) to end of follow-up (Day 18). |
| Change in 24-hour Urine Albumin:Creatinine Ratio (UACR) | From baseline (Day -3 to Day -1) to start of treatment (Day 4); and from baseline (Day -3 to Day-1) to end of treatment (Day 12 to 14) | Average change in mean 24-hour urine albumin:creatinine ratio (UACR) from average baseline to Day 4; and from average baseline values to average end of treatment values (Day 12 to 14). |
| Pharmacokinetics of Dapagliflozin on Day 4 and Day 14 | At pre-dose (Day 4) and at pre-dose, 1h, 2h, 4h post-dose (Day 14) | Dapagliflozin plasma concentration on Day 4 (pre-dose) and Day 14 (pre-dose, 1h, 2h, 4h post-dose) |
| Number of Patients With AEs and SAEs | From Day 1 until Day 18 (Follow-up) | An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. SAE is an AE that results in any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, or is a significant medical event. |
| Change in Plasma Volume From Baseline to End of Treatment | From baseline (Day 1) to end of treatment (Day 14) | Change in plasma volume from baseline to end of treatment (Day 14). |
Countries
Netherlands, Sweden
Participant flow
Recruitment details
The study was conducted between 12-Jul-2017 and 20-Mar-2020. Patients who met all the inclusion and none of the exclusion criteria were enrolled in the study.
Pre-assignment details
All study assessments were performed as per the schedule of assessment. No patients in Group 1 were enrolled into the Run-in set due to failure to meet inclusion exclusion criteria, screen failure, or other reasons. Due to unsatisfactory recruitment rate, it was decided that no more Group 1 patients would be enrolled in the study. Group 1 included type 2 diabetes mellitus (T2DM) patients with impaired kidney function and were to receive oral dose of dapagliflozin 10 mg/day from Day 1 to Day 14.
Participants by arm
| Arm | Count |
|---|---|
| Group 2 Type 2 diabetes mellitus (T2DM) patients with preserved kidney function received oral dose of dapagliflozin 10 mg/day from Day 1 to Day 14, following which they entered Follow-up Period from Day 15 to Day 19. | 17 |
| Group 3 Non-diabetic patients with impaired kidney function received oral dose of dapagliflozin 10 mg/day from Day 1 to Day 14, following which they entered Follow-up Period from Day 15 to Day 19. | 7 |
| Total | 24 |
Baseline characteristics
| Characteristic | Group 2 | Group 3 | Total |
|---|---|---|---|
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=80 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Between 18 and 80 years | 17 Participants | 7 Participants | 24 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 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 | 16 Participants | 7 Participants | 23 Participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 11 Participants | 5 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 7 |
| other Total, other adverse events | 6 / 17 | 2 / 7 |
| serious Total, serious adverse events | 0 / 17 | 0 / 7 |
Outcome results
Primary
Change in 24-hour Sodium Excretion From Baseline to Start of Treatment
Change in 24-hour sodium excretion during dapagliflozin treatment between baseline and average of Days 2 to 4 within each study group in patients with T2DM with preserved kidney function and in non-diabetics with impaired kidney function was assessed.
Time frame: From baseline (Day -3 to Day -1) to start of treatment (Day 2 to Day 4)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. It excluded primary efficacy variable data which may have been affected by protocol deviations as determined by medical monitor or agreed by study team. For Group 3, early termination of the study resulted in 6 evaluable patients. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in 24-hour Sodium Excretion From Baseline to Start of Treatment | -5.33 mmol/24 hour |
| Group 3 | Change in 24-hour Sodium Excretion From Baseline to Start of Treatment | -27.67 mmol/24 hour |
p-value: 0.446295% CI: [-19.542, 9.12]Mixed Models Analysis
Secondary
Change in 24-hour Glucose Excretion From Baseline to End of Treatment
Average change in 24-hour glucose excretion from average baseline values to average end of treatment values (Day 12 to 14)
Time frame: From baseline (Day -3 to Day -1) to end of treatment (Day 12 to 14)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented for Group 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in 24-hour Glucose Excretion From Baseline to End of Treatment | 283.40 mmol/24 hour |
| Group 3 | Change in 24-hour Glucose Excretion From Baseline to End of Treatment | 29.88 mmol/24 hour |
p-value: <0.000195% CI: [224.528, 398.064]Mixed Models Analysis
Secondary
Change in 24-hour Glucose Excretion From Baseline to Start of Treatment
Average change in 24-hour glucose excretion from average baseline values to average start of treatment values (Day 2 to 4).
Time frame: From baseline (Day -3 to Day -1) to start of treatment (Day 2 to 4)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented for Group 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in 24-hour Glucose Excretion From Baseline to Start of Treatment | 302.61 mmol/24 hour |
| Group 3 | Change in 24-hour Glucose Excretion From Baseline to Start of Treatment | 43.93 mmol/24 hour |
p-value: <0.000195% CI: [272.785, 416.905]Mixed Models Analysis
Secondary
Change in 24-hour Glucose Excretion From End of Treatment to Follow-up
Average change in 24-hour glucose excretion from average end of treatment values (Day 12 to 14) to average values during follow-up (Day 15 to 17).
Time frame: From end of treatment (Day 12 to 14) to follow-up (Day 15 to 17)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented for Group 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in 24-hour Glucose Excretion From End of Treatment to Follow-up | -168.43 mmol/24 hour |
| Group 3 | Change in 24-hour Glucose Excretion From End of Treatment to Follow-up | -37.02 mmol/24 hour |
p-value: <0.000195% CI: [-235.983, -170.162]Regression, Linear
Secondary
Change in 24-hour Sodium Excretion From Baseline to End of Treatment and From End of Treatment to Follow-up
Average change in 24-hour sodium excretion from average baseline values to average end of treatment values (Day 12 to 14); and from average end of treatment values (Day 12 to 14) to average values during follow-up (Day 15 to 17).
Time frame: From baseline (Day -3 to Day -1) to end of treatment (Day 12 to 14); and from end of treatment (Day 12 to 14) to follow-up (Day 15 to 17)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. It excluded primary efficacy variable data which may have been affected by protocol deviations as determined by medical monitor or agreed by study team. For Group 3, early termination of the study resulted in 6 evaluable patients. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 2 | Change in 24-hour Sodium Excretion From Baseline to End of Treatment and From End of Treatment to Follow-up | End of treatment vs baseline | 2.67 mmol/24 hour |
| Group 2 | Change in 24-hour Sodium Excretion From Baseline to End of Treatment and From End of Treatment to Follow-up | Follow-up vs end of treatment | 1.33 mmol/24 hour |
| Group 3 | Change in 24-hour Sodium Excretion From Baseline to End of Treatment and From End of Treatment to Follow-up | End of treatment vs baseline | -23.83 mmol/24 hour |
| Group 3 | Change in 24-hour Sodium Excretion From Baseline to End of Treatment and From End of Treatment to Follow-up | Follow-up vs end of treatment | 6.17 mmol/24 hour |
p-value: 0.784295% CI: [-24.817, 32.195]Mixed Models Analysis
p-value: 0.058195% CI: [-34.109, 0.664]Regression, Linear
Secondary
Change in 24-hour Urine Albumin:Creatinine Ratio (UACR)
Average change in mean 24-hour urine albumin:creatinine ratio (UACR) from average baseline to Day 4; and from average baseline values to average end of treatment values (Day 12 to 14).
Time frame: From baseline (Day -3 to Day -1) to start of treatment (Day 4); and from baseline (Day -3 to Day-1) to end of treatment (Day 12 to 14)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. It excluded primary efficacy variable data which may have been affected by protocol deviations as determined by medical monitor or agreed by study team. For Group 3, early termination of the study resulted in 6 evaluable patients. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 2 | Change in 24-hour Urine Albumin:Creatinine Ratio (UACR) | Start of treatment vs baseline | -0.07 mg/mmol |
| Group 2 | Change in 24-hour Urine Albumin:Creatinine Ratio (UACR) | End of treatment vs baseline | -0.04 mg/mmol |
| Group 2 | Change in 24-hour Urine Albumin:Creatinine Ratio (UACR) | Follow-up vs end of treatment | 0.07 mg/mmol |
| Group 3 | Change in 24-hour Urine Albumin:Creatinine Ratio (UACR) | End of treatment vs baseline | -7.28 mg/mmol |
| Group 3 | Change in 24-hour Urine Albumin:Creatinine Ratio (UACR) | Start of treatment vs baseline | -5.83 mg/mmol |
| Group 3 | Change in 24-hour Urine Albumin:Creatinine Ratio (UACR) | Follow-up vs end of treatment | -0.19 mg/mmol |
p-value: 0.002395% CI: [-3.299, -0.902]Mixed Models Analysis
p-value: <0.000195% CI: [-1.929, -1.256]Mixed Models Analysis
p-value: 0.000295% CI: [2.215, 5.553]Regression, Linear
Secondary
Change in Extracellular Volume From Baseline to End of Treatment
Change in extracellular volume from baseline to end of treatment (Day 14).
Time frame: From baseline (Day 1) to end of treatment (Day 14)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented for Group 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in Extracellular Volume From Baseline to End of Treatment | 0.1248 Litres |
| Group 3 | Change in Extracellular Volume From Baseline to End of Treatment | -0.1427 Litres |
p-value: 0.8795% CI: [-0.4631, 0.3984]Mixed Models Analysis
Secondary
Change in Extracellular Volume From Baseline to Start of Treatment
Change in extracellular volume from baseline to start of treatment (Day 4).
Time frame: From baseline (Day 1) to start of treatment (Day 4)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented for Group 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in Extracellular Volume From Baseline to Start of Treatment | -0.5783 Litres |
| Group 3 | Change in Extracellular Volume From Baseline to Start of Treatment | -0.4553 Litres |
p-value: 0.015795% CI: [-1.1914, -0.1511]Mixed Models Analysis
Secondary
Change in Extracellular Volume From End of Treatment to End of Follow-up
Change in extracellular volume from end of treatment (Day 14) to end of follow-up (Day 18).
Time frame: From end of treatment (Day 14) to end of follow-up (Day 18)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented for Group 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in Extracellular Volume From End of Treatment to End of Follow-up | 0.1784 Litres |
| Group 3 | Change in Extracellular Volume From End of Treatment to End of Follow-up | 0.1394 Litres |
p-value: 0.244695% CI: [-0.1358, 0.4795]Regression, Linear
Secondary
Change in Mean 24-hour Systolic Blood Pressure From Baseline to End of Treatment
Change in mean 24-hour systolic blood pressure from baseline to end of treatment (Day 13).
Time frame: From baseline (Day -1) to end of treatment (Day 13)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented for Group 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in Mean 24-hour Systolic Blood Pressure From Baseline to End of Treatment | -5.9385 mmHg |
| Group 3 | Change in Mean 24-hour Systolic Blood Pressure From Baseline to End of Treatment | -10.3290 mmHg |
p-value: 0.000395% CI: [-10.0379, -4.1595]Mixed Models Analysis
Secondary
Change in Mean 24-hour Systolic Blood Pressure From Baseline to Start of Treatment
Change in mean 24-hour systolic blood pressure from baseline to start of treatment (Day 4)
Time frame: From baseline (Day -1) to start of treatment (Day 4)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented for Group 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in Mean 24-hour Systolic Blood Pressure From Baseline to Start of Treatment | -5.4810 mmHg |
| Group 3 | Change in Mean 24-hour Systolic Blood Pressure From Baseline to Start of Treatment | -8.9730 mmHg |
p-value: 0.004795% CI: [-8.5459, -1.9856]Mixed Models Analysis
Secondary
Change in Mean 24-hour Systolic Blood Pressure From End of Treatment to End of Follow-up
Change in mean 24-hour systolic blood pressure from end of treatment (Day 13) to end of follow-up (Day 18).
Time frame: From end of treatment (Day 13) to end of follow-up (Day 18)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented for Group 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in Mean 24-hour Systolic Blood Pressure From End of Treatment to End of Follow-up | 2.5140 mmHg |
| Group 3 | Change in Mean 24-hour Systolic Blood Pressure From End of Treatment to End of Follow-up | -2.6590 mmHg |
p-value: 0.559295% CI: [-1.9894, 3.4468]Regression, Linear
Secondary
Change in Plasma Volume From Baseline to End of Treatment
Change in plasma volume from baseline to end of treatment (Day 14).
Time frame: From baseline (Day 1) to end of treatment (Day 14)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented for Group 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in Plasma Volume From Baseline to End of Treatment | -0.2122 Litres |
| Group 3 | Change in Plasma Volume From Baseline to End of Treatment | 2.0557 Litres |
p-value: 0.165995% CI: [-1.0761, 0.2125]Mixed Models Analysis
Secondary
Change in Plasma Volume From Baseline to Start of Treatment
Change in plasma volume from baseline to start of treatment (Day 4).
Time frame: From baseline (Day 1) to start of treatment (Day 4)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented for Group 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in Plasma Volume From Baseline to Start of Treatment | -0.1440 Litres |
| Group 3 | Change in Plasma Volume From Baseline to Start of Treatment | -0.1139 Litres |
p-value: 0.928895% CI: [-0.7274, 0.7904]Mixed Models Analysis
Secondary
Change in Plasma Volume From End of Treatment to End of Follow-up
Change in plasma volume from end of treatment (Day 14) to end of follow-up (Day 18).
Time frame: From end of treatment (Day 14) to end of follow-up (Day 18)
Population: Evaluable patient set: all patients who dispensed at least one dose of study drug. Due to insufficient number of patients recruited, no statistical conclusions were derived, and no confidence intervals or p-values are presented for Group 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 | Change in Plasma Volume From End of Treatment to End of Follow-up | 0.6464 Litres |
p-value: 0.01995% CI: [0.0963, 0.8548]Regression, Linear
Secondary
Number of Patients With AEs and SAEs
An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. SAE is an AE that results in any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, or is a significant medical event.
Time frame: From Day 1 until Day 18 (Follow-up)
Population: Safety set: all patients who received at least one dose of study drug and had data from at least one post-dose safety assessment available were included in the safety set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 2 | Number of Patients With AEs and SAEs | Hypoglycaemia AEs leading to permanent discontinuation of dapagliflozin | 0 Patients |
| Group 2 | Number of Patients With AEs and SAEs | Any AE | 6 Patients |
| Group 2 | Number of Patients With AEs and SAEs | AEs judged as causally related to dapagliflozin | 4 Patients |
| Group 2 | Number of Patients With AEs and SAEs | AEs leading to death | 0 Patients |
| Group 2 | Number of Patients With AEs and SAEs | SAEs (including outcomes = death) | 0 Patients |
| Group 2 | Number of Patients With AEs and SAEs | SAEs causally related to dapagliflozin | 0 Patients |
| Group 2 | Number of Patients With AEs and SAEs | AEs leading to permanent discontinuation of dapagliflozin | 0 Patients |
| Group 2 | Number of Patients With AEs and SAEs | SAEs leading to permanent discontinuation of dapagliflozin | 0 Patients |
| Group 2 | Number of Patients With AEs and SAEs | Hypoglycaemia AEs | 0 Patients |
| Group 3 | Number of Patients With AEs and SAEs | AEs leading to permanent discontinuation of dapagliflozin | 0 Patients |
| Group 3 | Number of Patients With AEs and SAEs | SAEs causally related to dapagliflozin | 0 Patients |
| Group 3 | Number of Patients With AEs and SAEs | SAEs (including outcomes = death) | 0 Patients |
| Group 3 | Number of Patients With AEs and SAEs | Any AE | 2 Patients |
| Group 3 | Number of Patients With AEs and SAEs | Hypoglycaemia AEs | 0 Patients |
| Group 3 | Number of Patients With AEs and SAEs | AEs judged as causally related to dapagliflozin | 0 Patients |
| Group 3 | Number of Patients With AEs and SAEs | SAEs leading to permanent discontinuation of dapagliflozin | 0 Patients |
| Group 3 | Number of Patients With AEs and SAEs | AEs leading to death | 0 Patients |
| Group 3 | Number of Patients With AEs and SAEs | Hypoglycaemia AEs leading to permanent discontinuation of dapagliflozin | 0 Patients |
Secondary
Pharmacokinetics of Dapagliflozin on Day 4 and Day 14
Dapagliflozin plasma concentration on Day 4 (pre-dose) and Day 14 (pre-dose, 1h, 2h, 4h post-dose)
Time frame: At pre-dose (Day 4) and at pre-dose, 1h, 2h, 4h post-dose (Day 14)
Population: Pharmacokinetic analysis set: all patients who were dispensed at least one dose of the study drug and for whom at least one of the plasma concentration samples were available and who had no important protocol deviations judged to impact the analysis of the PK data. Here, number analyzed in each row signifies only the patients with available data that were analyzed for that specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group 2 | Pharmacokinetics of Dapagliflozin on Day 4 and Day 14 | Day 14, Pre-dose | 4.54 ng/mL | Geometric Coefficient of Variation 46.6 |
| Group 2 | Pharmacokinetics of Dapagliflozin on Day 4 and Day 14 | Day 14, 2 h | 46.47 ng/mL | Geometric Coefficient of Variation 49.3 |
| Group 2 | Pharmacokinetics of Dapagliflozin on Day 4 and Day 14 | Day 14, 1 h | 57.46 ng/mL | Geometric Coefficient of Variation 110.66 |
| Group 2 | Pharmacokinetics of Dapagliflozin on Day 4 and Day 14 | Day 14, 4 h | 29.71 ng/mL | Geometric Coefficient of Variation 47.38 |
| Group 2 | Pharmacokinetics of Dapagliflozin on Day 4 and Day 14 | Day 4, Pre-dose | 4.58 ng/mL | Geometric Coefficient of Variation 134.88 |
| Group 3 | Pharmacokinetics of Dapagliflozin on Day 4 and Day 14 | Day 14, 4 h | 47.83 ng/mL | Geometric Coefficient of Variation 100.41 |
| Group 3 | Pharmacokinetics of Dapagliflozin on Day 4 and Day 14 | Day 4, Pre-dose | 19.78 ng/mL | Geometric Coefficient of Variation 116.54 |
| Group 3 | Pharmacokinetics of Dapagliflozin on Day 4 and Day 14 | Day 14, Pre-dose | 15.26 ng/mL | Geometric Coefficient of Variation 41.97 |
| Group 3 | Pharmacokinetics of Dapagliflozin on Day 4 and Day 14 | Day 14, 1 h | 63.83 ng/mL | Geometric Coefficient of Variation 150.41 |
| Group 3 | Pharmacokinetics of Dapagliflozin on Day 4 and Day 14 | Day 14, 2 h | 60.41 ng/mL | Geometric Coefficient of Variation 140.69 |