E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic kidney disease in type 2 diabetes mellitus |
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E.1.1.1 | Medical condition in easily understood language |
Chronic kidney disease, a long-term progressive decrease in the kidneys' ability to work properly, and type 2 diabetes, a condition characterized by high blood sugar levels |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045250 |
E.1.2 | Term | Type II diabetes mellitus with renal manifestations |
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 |
The primary objective is to demonstrate that combination therapy using finerenone and empagliflozin is superior in reducing UACR than either empagliflozin or finerenone alone. |
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E.2.2 | Secondary objectives of the trial |
The secondary outcomes are: - To further investigate the efficacy of combination therapy using finerenone and empagliflozin versus either finerenone or empagliflozin alone. - To evaluate the safety of combination therapy using finerenone and empagliflozin versus either finerenone or empagliflozin alone. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participant with a clinical diagnosis of chronic kidney disease (CKD) and the following: a. In Part A: eGFR 40-90 ml/min/1.73m^2 (with no more than 20% having an eGFR >75 ml/min/1.73m^2) using Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) formula at screening visit and at least one historical value of eGFR <60 mL/min/1.73 m^2 within 3 months or have a registered diagnosis of CKD. b. In Part B: eGFR 30-90 ml/min/1.73m^2 (with no more than 20% having an eGFR >75 ml/min/1.73m^2) using CKD-EPI formula at screening visit and at least one historical value of eGFR <60 mL/min/1.73 m^2 within 3 months or have a registered diagnostic of CKD. c. 100 ≤UACR <5000 mg/g at screening visit (mean value from 3 morning void samples) and documentation of albuminuria/proteinuria (quantitative or semi-quantitative measurement) in the participant's medical records at least 3 months prior to screening 2. Participant with type 2 diabetes (T2D) as defined by the American Diabetes Association (ADA 2021), with glycated hemoglobin (HbA1c) at screening <11%. 3. Participant treated with the clinically maximum tolerated dose, as per investigator judgment, of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), but not both, for more than 1 month at screening visit. |
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E.4 | Principal exclusion criteria |
1. Participants with type 1 diabetes (T1D). 2. Participant with hepatic insufficiency classified as Child-Pugh C. 3. Participant with blood pressure at Day 1 visit (Visit 2) higher than 160 SBP or 100 DBP or SBP lower than 90 mmHg. 4. Participant currently treated with a sodium/glucose cotransporter-2 inhibitor (SGLT2i) or SGLT-1/2i or who received a SGLT2i or SGLT-1/2i which cannot be discontinued at least 8 weeks prior to the screening visit and during study intervention treatment. 5. Participant treated with another mineralocorticoid receptor antagonist (MRA) (e.g., eplerenone, esaxerenone, spironolactone, canrenone), a renin inhibitor, potassium supplements, a potassium sparing diuretic (e.g., amiloride, triamterene), a potassium binder agent, or angiotensin receptor-neprilysin inhibitor (ARNI) which cannot be discontinued at least 8 weeks prior to the screening visit and during study intervention treatment. 6. Participants currently treated or who were treated with Finerenone (Kerendia©) within 8 weeks prior to the screening visit. 7. Participant with serum/plasma potassium (K+) above 4.8 mmol/L at screening (central laboratory value). |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Mean ratio of change from baseline to Day 180 in Urinary albumin to creatinine ratio (UACR) for the combination therapy group, to empagliflozin alone 2. Mean ratio of change from baseline to Day 180 in UACR for the combination therapy group, to finerenone alone |
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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) |
1. Relative change in UACR between end of treatment visit and 30 days after end of treatment visit 2. Relative change in UACR between 30 days after end of treatment visit and baseline 3. Relative change in UACR category (>30%, >40%, >50%) at 180 days 4. Ratio of change from baseline in eGFR at 30 days 5. eGFR decline greater than 30% at 30 days from baseline 6. Ratio of change in eGFR at 180 days and 210 days from day 30 7. Number of participants with of AKI events 8. Total number of AKI events 9. Number of participants with hyperkalemia events (moderate hyperkalemia [5.5 <K+ ≤6.0 mmol/L], severe hyperkalemia [K+ >6.0 mmol/L]) 10. Total number of hyperkalemia events (moderate hyperkalemia [5.5 <K+ ≤6.0 mmol/L], severe hyperkalemia [K+ >6.0 mmol/L]) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to 210 days 2. Up to 210 days 3. Up to 180 days 4. Up t0 30 days 5. Up to 30 days 6. Up to 210 days 7. to 23. Up to 180 days |
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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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Taiwan |
Canada |
Israel |
Japan |
Korea, Republic of |
United States |
Belgium |
Denmark |
France |
Germany |
Italy |
Netherlands |
Spain |
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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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Last visit of the last participant in the study |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 18 |