Chronic Kidney Diseases, Proteinuria
Conditions
Keywords
chronic kidney disease, non diabetic
Brief summary
This study tests the hypothesis that dapagliflozin lowers proteinuria in patients with non-diabetic chronic kidney disease.
Detailed description
Despite optimal treatment with renin-angiotensin-aldosterone-system (RAAS) inhibitors, many patients with non-diabetic kidney disease show progressive kidney function loss, which is associated with high residual proteinuria. Novel treatment strategies are therefore required to further decrease proteinuria and to slow kidney function decline. Dapagliflozin is a sodium-glucose transport (SGLT2) inhibitor and inhibits the reabsorption of glucose and sodium in the proximal tubule. The increased natriuresis following dapagliflozin administration normalizes tubuloglomerular feedback resulting in a reduction in intra-glomerular hypertension, which is in turn manifested by acute reversible reductions in glomerular filtration rate and albuminuria. Since many etiologies of non-diabetic nephropathy are characterized by intraglomerular hypertension, we hypothesize that dapagliflozin acutely decreases GFR and proteinuria in patients without diabetes at risk of progressive kidney function loss via a glucose independent hemodynamic mechanism.
Interventions
DRUGDapagliflozin 10mg
Tablet
Sponsors
AstraZeneca
Hiddo Lambers Heerspink
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Intervention model description
A Randomized Double Blind 6-Weeks Cross-over
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥18 and ≤75 years * Urinary protein excretion \> 500 mg/g and ≤ 3500 mg/g in a 24-hr urine collection eGFR ≥ 25 mL/min/1.73m2 * On a stable dose of an ACEi or ARB for at least 4 weeks prior to randomization * Willing to sign informed consent * Women of Child-Bearing Potential (WOCBP): * WOCBP must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized. * WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 0 to 72 hours before the first dose of study drug. * Women must not be breast-feeding. WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal.
Exclusion criteria
* Diagnosis of type 1 or type 2 diabetes mellitus * Urinary protein excretion \> 3500 mg/day * Peripheral Vascular Disease * Autosomal dominant polycystic kidney disease or autosomal recessive polycystic kidney disease, lupus nephritis, or ANCA-associated vasculitis * Indication for immunosuppressants as per the treating physician's judgment. * Receiving cytotoxic therapy, immunosuppressive therapy, or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment. * Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin. * Use of co-interventional treatments (outlined in section 4.2 of the protocol) within 6 weeks of screening will not be allowed. * Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following: * History of active inflammatory bowel disease within the last six months; * Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; * Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months; * Pancreatic injury or pancreatitis within the last six months; * Evidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3x ULN at the screening visit, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt; * Evidence of urinary obstruction of difficulty in voiding at screening * History of severe hypersensitivity or contraindications to dapagliflozin * Subject who, in the assessment of the investigator, may be at risk for dehydration or volume depletion that may affect the interpretation of efficacy or safety data * Participation in any clinical investigation within 3 months prior to initial dosing. * Donation or loss of 400 ml or more of blood within 8 weeks prior to initial dosing. * History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening. * History of noncompliance to medical regimens or unwillingness to comply with the study protocol. * Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study. * Pregnancy or breastfeeding * WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and up to 4 weeks after the last dose of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24-hr Proteinuria With Dapagliflozin for Six Weeks Relative to Placebo in Patients With Non-diabetic Kidney Disease and Proteinuria 500 mg/Day on Stable Angiotensin-converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Treatment. | 6 weeks | bioequivalence |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 0, 3, 6, 12, 15, 18, 24 | bioequivalence |
| Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | week 0, 3, 6, 12, 15, 18, 24 | bioequivalence |
| Effect of Dapagliflozin 10 mg/d Compared to Placebo on 6-keto-Prostaglandin F1 Alpha/Creatinine Ratio | Baseline, Week 6 | bioequivalence |
| Safety of Dapagliflozin vs. Placebo - the Number of Participatns With Hypoglycemic Events and/or Serious Adverse Events | week 0-26 | safety |
| Effect of Dapagliflozin 10 mg/d Compared to Placebo on Glomerular Filtration Rate (GFR) Using Iohexol Clearance | 6 weeks | bioequivalence |
| Effect of Dapagliflozin 10 mg/d Compared to Placebo on Prostaglandin E2/Creatinine Ratio | Baseline, Week 6 | bioequivalence |
| Effect of Dapagliflozin 10 mg/d Compared to Placebo on Thromboxane B2/Creatinine Ratio | Baseline, Week 6 | bioequivalence |
| Effect of Dapagliflozin 10 mg/d Compared to Placebo on PGEM/Creatinine Ratio | Baseline, Week 6 | bioequivalence |
| Effect of Dapagliflozin 10 mg/d Compared to Placebo on NTproBNP | Baseline (week 0, week 12), Week 6 + 18 (pooled) | bioequivalence |
| Effect of Dapagliflozin 10 mg/d Compared to Placebo on Adenosine/Creatinine Ratio | Baseline, Week 6 | bioequivalence |
Countries
Canada, Malaysia, Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dapagliflozin 10mg Tablet 10 mg Green, plain, diamond shaped, film coated tablet (orally)
Dapagliflozin 10mg: Tablet | 27 |
| Placebo Matching Dapagliflozin Tablet Green, plain, diamond shaped, film coated tablet. Does not contain active ingredient
Dapagliflozin 10mg: Tablet | 26 |
| Total | 53 |
Baseline characteristics
| Characteristic | Dapagliflozin 10mg Tablet | Placebo Matching Dapagliflozin Tablet | Total |
|---|---|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 10 | 51 years STANDARD_DEVIATION 16 | 51 years STANDARD_DEVIATION 13 |
| mGFR | 58.9 ml/min/1.73m2 STANDARD_DEVIATION 20.7 | 57.8 ml/min/1.73m2 STANDARD_DEVIATION 25.5 | 58.3 ml/min/1.73m2 STANDARD_DEVIATION 23 |
| Proteinuria | 1170 mg/24h | 1105 mg/24h | 1110 mg/24h |
| Race/Ethnicity, Customized Asia | 11 Participants | 6 Participants | 17 Participants |
| Race/Ethnicity, Customized Caucasian | 12 Participants | 17 Participants | 29 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Female | 9 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Male | 18 Participants | 18 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 52 |
| other Total, other adverse events | 17 / 53 | 13 / 52 |
| serious Total, serious adverse events | 1 / 53 | 1 / 52 |
Outcome results
Primary
Change in 24-hr Proteinuria With Dapagliflozin for Six Weeks Relative to Placebo in Patients With Non-diabetic Kidney Disease and Proteinuria 500 mg/Day on Stable Angiotensin-converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Treatment.
bioequivalence
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dapagliflozin 10mg Tablet | Change in 24-hr Proteinuria With Dapagliflozin for Six Weeks Relative to Placebo in Patients With Non-diabetic Kidney Disease and Proteinuria 500 mg/Day on Stable Angiotensin-converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Treatment. | -15.04 % change from baseline |
| Placebo Matching Dapagliflozin Tablet | Change in 24-hr Proteinuria With Dapagliflozin for Six Weeks Relative to Placebo in Patients With Non-diabetic Kidney Disease and Proteinuria 500 mg/Day on Stable Angiotensin-converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Treatment. | -15.80 % change from baseline |
Secondary
Effect of Dapagliflozin 10 mg/d Compared to Placebo on 6-keto-Prostaglandin F1 Alpha/Creatinine Ratio
bioequivalence
Time frame: Baseline, Week 6
Population: Difference in no. of participants at week 6 due to missed visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on 6-keto-Prostaglandin F1 Alpha/Creatinine Ratio | Baseline | 0.1170 pg/mmol | Standard Deviation 0.0422 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on 6-keto-Prostaglandin F1 Alpha/Creatinine Ratio | Week 6 | 0.1281 pg/mmol | Standard Deviation 0.045 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on 6-keto-Prostaglandin F1 Alpha/Creatinine Ratio | Baseline | 0.1167 pg/mmol | Standard Deviation 0.1079 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on 6-keto-Prostaglandin F1 Alpha/Creatinine Ratio | Week 6 | 0.1203 pg/mmol | Standard Deviation 0.0554 |
Secondary
Effect of Dapagliflozin 10 mg/d Compared to Placebo on Adenosine/Creatinine Ratio
bioequivalence
Time frame: Baseline, Week 6
Population: Difference in no. of participants at week 6 due to missed visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Adenosine/Creatinine Ratio | Baseline | 0.2020 micromol/mmol | Standard Deviation 0.1566 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Adenosine/Creatinine Ratio | Week 6 | 0.2218 micromol/mmol | Standard Deviation 0.1706 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Adenosine/Creatinine Ratio | Baseline | 0.1949 micromol/mmol | Standard Deviation 0.1529 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Adenosine/Creatinine Ratio | Week 6 | 0.2373 micromol/mmol | Standard Deviation 0.2529 |
Secondary
Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight
bioequivalence
Time frame: week 0, 3, 6, 12, 15, 18, 24
Population: Several participants missed some of their visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 6 | 80.419 kg | Standard Deviation 16.125 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 15 | 77.046 kg | Standard Deviation 15.1826 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 3 | 78.892 kg | Standard Deviation 15.8944 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 18 | 77.488 kg | Standard Deviation 14.9676 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 12 | 78.712 kg | Standard Deviation 15.0825 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 24 | 77.204 kg | Standard Deviation 12.4649 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 0 | 79.646 kg | Standard Deviation 15.5147 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 24 | 84.163 kg | Standard Deviation 22.2775 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 0 | 86.196 kg | Standard Deviation 23.9748 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 3 | 83.242 kg | Standard Deviation 21.8429 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 6 | 85.185 kg | Standard Deviation 24.2097 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 12 | 85.265 kg | Standard Deviation 24.3126 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 15 | 83.048 kg | Standard Deviation 22.8179 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight | Week 18 | 86.144 kg | Standard Deviation 24.4698 |
Secondary
Effect of Dapagliflozin 10 mg/d Compared to Placebo on Glomerular Filtration Rate (GFR) Using Iohexol Clearance
bioequivalence
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Glomerular Filtration Rate (GFR) Using Iohexol Clearance | -6.3 mL/min per 1.73m2 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Glomerular Filtration Rate (GFR) Using Iohexol Clearance | 0.3 mL/min per 1.73m2 |
Secondary
Effect of Dapagliflozin 10 mg/d Compared to Placebo on NTproBNP
bioequivalence
Time frame: Baseline (week 0, week 12), Week 6 + 18 (pooled)
Population: Difference in no. of participants at week 6 due to missed visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on NTproBNP | Baseline (week 0 + 12) | 118.8 ng/L | Standard Deviation 151.18 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on NTproBNP | Week 6 + 18 | 108.7 ng/L | Standard Deviation 148.74 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on NTproBNP | Baseline (week 0 + 12) | 125.0 ng/L | Standard Deviation 161.1 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on NTproBNP | Week 6 + 18 | 152.6 ng/L | Standard Deviation 277.74 |
Secondary
Effect of Dapagliflozin 10 mg/d Compared to Placebo on PGEM/Creatinine Ratio
bioequivalence
Time frame: Baseline, Week 6
Population: Difference in no. of participants at week 6 due to missed visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on PGEM/Creatinine Ratio | Baseline | 0.0989 pg/mmol | Standard Deviation 0.0559 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on PGEM/Creatinine Ratio | Week 6 | 0.0965 pg/mmol | Standard Deviation 0.0538 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on PGEM/Creatinine Ratio | Baseline | 0.0948 pg/mmol | Standard Deviation 0.0552 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on PGEM/Creatinine Ratio | Week 6 | 0.0963 pg/mmol | Standard Deviation 0.0565 |
Secondary
Effect of Dapagliflozin 10 mg/d Compared to Placebo on Prostaglandin E2/Creatinine Ratio
bioequivalence
Time frame: Baseline, Week 6
Population: Difference in no. of participants at week 6 due to missed visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Prostaglandin E2/Creatinine Ratio | Baseline | 0.1131 pg/mmol | Standard Deviation 0.1498 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Prostaglandin E2/Creatinine Ratio | Week 6 | 0.1702 pg/mmol | Standard Deviation 0.2656 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Prostaglandin E2/Creatinine Ratio | Baseline | 0.0980 pg/mmol | Standard Deviation 0.1034 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Prostaglandin E2/Creatinine Ratio | Week 6 | 0.0946 pg/mmol | Standard Deviation 0.1428 |
Secondary
Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure
bioequivalence
Time frame: week 0, 3, 6, 12, 15, 18, 24
Population: Due to several missed visits the no. of analyzed participants is not the same for all visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 0 SBP | 127.4 mm Hg | Standard Deviation 16.44 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 3 SBP | 124.3 mm Hg | Standard Deviation 13.93 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 6 SBP | 120.4 mm Hg | Standard Deviation 13.87 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 12 SBP | 125.6 mm Hg | Standard Deviation 15.86 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 15 SBP | 125.0 mm Hg | Standard Deviation 15.05 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 18 SBP | 123.5 mm Hg | Standard Deviation 10.94 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 24 SBP | 123.6 mm Hg | Standard Deviation 14.9 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 0 DBP | 77.2 mm Hg | Standard Deviation 8.68 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 3 DBP | 78.0 mm Hg | Standard Deviation 6.81 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 6 DBP | 74.5 mm Hg | Standard Deviation 6.8 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 12 DBP | 77.6 mm Hg | Standard Deviation 7.83 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 15 DBP | 77.6 mm Hg | Standard Deviation 7.18 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 18 DBP | 76.6 mm Hg | Standard Deviation 7.44 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 24 DBP | 74.5 mm Hg | Standard Deviation 6.36 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 12 DBP | 74.7 mm Hg | Standard Deviation 9.05 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 0 SBP | 124.6 mm Hg | Standard Deviation 13.1 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 0 DBP | 75.2 mm Hg | Standard Deviation 7.77 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 3 SBP | 121.8 mm Hg | Standard Deviation 9.9 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 18 DBP | 72.7 mm Hg | Standard Deviation 9.3 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 6 SBP | 123.2 mm Hg | Standard Deviation 12.27 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 3 DBP | 74.5 mm Hg | Standard Deviation 6.82 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 12 SBP | 125.2 mm Hg | Standard Deviation 14.02 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 15 DBP | 74.3 mm Hg | Standard Deviation 8.39 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 15 SBP | 122.8 mm Hg | Standard Deviation 13.2 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 6 DBP | 74.4 mm Hg | Standard Deviation 7.84 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 18 SBP | 120.9 mm Hg | Standard Deviation 16.48 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | Week 24 DBP | 75.1 mm Hg | Standard Deviation 8.69 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure | week 24 SBP | 123.9 mm Hg | Standard Deviation 14.67 |
Secondary
Effect of Dapagliflozin 10 mg/d Compared to Placebo on Thromboxane B2/Creatinine Ratio
bioequivalence
Time frame: Baseline, Week 6
Population: Difference in no. of participants at week 6 due to missed visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Thromboxane B2/Creatinine Ratio | Baseline | 0.0921 pg/mmol | Standard Deviation 0.0569 |
| Dapagliflozin 10mg Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Thromboxane B2/Creatinine Ratio | Week 6 | 0.1058 pg/mmol | Standard Deviation 0.1005 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Thromboxane B2/Creatinine Ratio | Baseline | 0.0963 pg/mmol | Standard Deviation 0.047 |
| Placebo Matching Dapagliflozin Tablet | Effect of Dapagliflozin 10 mg/d Compared to Placebo on Thromboxane B2/Creatinine Ratio | Week 6 | 0.0930 pg/mmol | Standard Deviation 0.0499 |
Secondary
Safety of Dapagliflozin vs. Placebo - the Number of Participatns With Hypoglycemic Events and/or Serious Adverse Events
safety
Time frame: week 0-26
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dapagliflozin 10mg Tablet | Safety of Dapagliflozin vs. Placebo - the Number of Participatns With Hypoglycemic Events and/or Serious Adverse Events | Serious adverse event | 1 participants |
| Dapagliflozin 10mg Tablet | Safety of Dapagliflozin vs. Placebo - the Number of Participatns With Hypoglycemic Events and/or Serious Adverse Events | Hypoglycemic episode | 0 participants |
| Placebo Matching Dapagliflozin Tablet | Safety of Dapagliflozin vs. Placebo - the Number of Participatns With Hypoglycemic Events and/or Serious Adverse Events | Serious adverse event | 1 participants |
| Placebo Matching Dapagliflozin Tablet | Safety of Dapagliflozin vs. Placebo - the Number of Participatns With Hypoglycemic Events and/or Serious Adverse Events | Hypoglycemic episode | 0 participants |