E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027525 |
E.1.2 | Term | Microalbuminuria |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the albuminuria lowering effects of dapagliflozin in subjects with and without diabetes or hypertension and persistent elevated albuminuria. |
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E.2.2 | Secondary objectives of the trial |
To assess effects of dapagliflozin compared to placebo on the following parameters:
o Systolic and diastolic blood pressure
o Body weight
o Hba1c
o eGFR
o Proportion of patients with ≥30%, 40%, 50% reduction in UACR from baseline at week 24.
To assess the safety of dapagliflozin |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 45 to 80 years
• Persistent urinary albumin:creatinine ratio (UACR) ≥ 2.5 mg/mmol (~25 mg/g)
• Willing to sign informed consent
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E.4 | Principal exclusion criteria |
• Diagnosis of type 1 diabetes mellitus
• eGFR < 25 ml/min/1.73m2
• UACR > 3500 mg/g
• Concurrent treatment with SGLT2 inhibitor
• Receiving immunosuppressive therapy within 6 months prior to enrolment
• History of diabetic ketoacidosis
• Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin.
• Initiation or changes in the dose of interventions in the renin-angiotensin-aldosterone-system, diuretics, GLP-1 receptor agonists 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:
o History of active inflammatory bowel disease within the last six months;
o Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
o Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months;
o Pancreatic injury or pancreatitis within the last six months;
o 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;
o Evidence of urinary obstruction or difficulty in voiding at screening
• History of severe hypersensitivity or contraindications to dapagliflozin
• Subjects 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 intervention study within 3 months 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in first morning UACR from baseline |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Changes from baseline in:
• Systolic / diastolic blood pressure
• Body weight
• Hba1c
• eGFR
• Number of patients with ≥30%, 40%, 50% reduction in UACR from baseline at week 24
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |