E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic kidney disease with and without type 2 diabetes |
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E.1.1.1 | Medical condition in easily understood language |
Chronic kidney disease with and without type 2 diabetes |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076411 |
E.1.2 | Term | Chronic kidney disease stage 4 |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076410 |
E.1.2 | Term | Chronic kidney disease stage 3 |
E.1.2 | System Organ Class | 100000004857 |
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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 |
The difference of Ang 1-7 increase from baseline between a 3-month treatment with empagliflozin on top of ACEi treatment compared to ACEi treatment alone |
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E.2.2 | Secondary objectives of the trial |
The following parameters will be assessed after 3 months of empagliflozin treatment:
• Mean quantitative changes of baseline multiple RAS effector angiotensin levels • Mean changes of baseline Ang II levels • Mean changes of baseline specific protein amount on HDL • Mean changes in specific renal parameters from baseline and after 3 months of empagaliflozin treatment (albuminuria reduction, renal function) • Mean changes from baseline relevant blood parameters (HbA1c, β-hydroxybutyrat, elektrolytes, lipids, etc.) • Mean changes from baseline urinary electrolyte levels and after 3 months of empagaliflozin treatment • Mean changes from baseline urinary RAS metabolites (angiotensinogen, ACE and ACE2 levels, ACE2 activity) • Mean changes in baseline blood pressure • Mean changes in baseline body weight • Mean changes in body fluid status • Mean changes in baseline OCR and ECAR in PBMCs • Mean changes in salt sensitivity
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
CKD patients with type 2 diabetes • Estimated GFR (calculated with the MDRD formula) between 15 and 59 ml/min (with CKD stage IIIa/b to IV) • Albumin excretion rates of >30 mg/24 hours (UACR >30 mg/g) • Fasting plasma glucose levels >126 mg/dl [7mmol/L] or HbA1c levels >6.5% (Definition of type 2 diabetes according to the diagnostic criteria set forth by the American Diabetes Association in 2009)
CKD patients without diabetes • Estimated GFR (calculated with the MDRD formula) between 15 and 59 ml/min (with CKD stage IIIa/b to IV) • Albumin excretion rates of >30 mg/24 hours (UACR >30 mg/g)
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E.4 | Principal exclusion criteria |
CKD patients with type 2 diabetes • Age <18 years • Severely impaired renal function (eGFR <15ml/min) • Hyperkalemia above 5,1mmol/L • Hypotension (systolic blood pressure lower than 120 mmHg on ambulatory measurement) • Pregnant patients • Patients planning pregnancy • Body mass index < 18.5 kg/m2
• Total urinary protein excretion ≥ 3.5 g/d
CKD patients without diabetes • Age <18 years • Diabetic kidney disease • Severely impaired renal function (eGFR <15ml/min) • Hyperkalemia above 5.1mmol/L • Hypotension (systolic blood pressure lower than 120 mmHg on ambulatory measurement) • Pregnant patients • Patients planning pregnancy • Body mass index < 18.5 kg/m2 • Total urinary protein excretion ≥ 3.5 g/d
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint will be the difference of the extent of Ang 1-7 upregulation determined by mass-spectrometric measurement of Ang 1-7 concentrations after a 3-month treatment with empagliflozin in addition to ACEi treatment alone. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after a three-month intake of empagliflozin. |
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E.5.2 | Secondary end point(s) |
• Mean quantitative changes of baseline multiple RAS effector angiotensin levels after 3 months of empagaliflozin treatment • Mean changes of baseline Ang II levels after 3 months of empagaliflozin treatment • Mean changes of baseline specific protein amount on HDL after 3 months of empagaliflozin treatment • Mean changes in specific renal parameters from baseline and after 3 months of empagaliflozin treatment (albuminuria reduction, renal function) • Mean changes from baseline relevant blood parameters (HbA1c, β-hydroxybutyrat, elektrolytes, lipids, etc.) after 3 months of empagaliflozin treatment • Mean changes from baseline urinary electrolyte levels and after 3 months of empagaliflozin treatment • Mean changes from baseline urinary RAS metabolites (angiotensinogen, ACE and ACE2 levels, ACE2 activity) after 3 months of empagaliflozin treatment • Mean changes in baseline blood pressure after 3 months of empagaliflozin treatment • Mean changes in baseline body weight after 3 months of empagaliflozin treatment • Mean changes in body fluid status after 3 months of empagaliflozin treatment • Mean changes in baseline oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) in peripheral peripheral blood mononuclear cells (PBMCs) after 3 months of empagliflozin treatment • Mean changes in salt sensitivity after 3 months of empagliflozin treatment
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after a three-month intake of empagliflozin. |
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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 | Yes |
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 | No |
E.6.11 | Pharmacogenomic | No |
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 | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |