A Study to Test Whether Different Doses of BI 690517 Alone or in Combination With Empagliflozin Improve Kidney Function in People With Chronic Kidney Disease

Study Overview
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Brief Summary
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This study is open to adults with chronic kidney disease. People with and without type 2 diabetes can take part in this study. The purpose of this study is to find out whether a medicine called BI 690517 improves kidney function in people with chronic kidney disease when taken alone or in combination with a medicine called empagliflozin. In the first part of the study, participants take empagliflozin or placebo as tablets every day for 2 months. Placebo tablets look like empagliflozin tablets but do not contain any medicine. In the second part, participants are divided into several groups. Depending on the group, the participants then additionally take different doses of BI 690517 or placebo as tablets for 3.5 months. In this case, placebo tablets look like BI 690517 tablets but do not contain any medicine. Participants are in the study for about 6 months. During this time, they visit the study site about 12 times. Where possible, about 4 of the 12 visits can be done at the participant's home instead of the study site. The trial staff may also contact the participants by phone or video call. Participants collect urine samples at home. These samples are then analysed to assess kidney function. At the end of the trial the results are compared between the different groups. The doctors also regularly check participants' health and take note of any unwanted effects.

Official Title
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Randomised, Double-blind, Placebo-controlled and Parallel Dose Group Trial to Investigate Efficacy and Safety of Multiple Doses of Oral BI 690517 Over 14 Weeks, Alone and in Combination With Empagliflozin, in Patients With Diabetic and Non-diabetic Chronic Kidney Disease

Conditions
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Kidney Disease, Chronic

Intervention / Treatment
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* Drug: BI 690517
* Drug: Placebo to BI 690517
* Drug: Empagliflozin
* Drug: Placebo to empagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Signed and dated written informed consent in accordance with International Council on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial. Male or female patients of legal adult age (according to local legislation) and aged ≥ 18 years at time of consent. estimated Glomerular Filtration Rate (eGFR, Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) ≥ 30 and < 90 mL/min/1.73 m2 at Visit 1 by central laboratory analysis. Urine Albumin Creatinine Ratio (UACR) ≥ 200 and < 5,000 mg/g in spot urine (midstream urine sample) by central laboratory analysis at Visit 1.1 If the patient is taking any of the following medications they should be on a stable dose for at least 4 weeks prior to visit 1 and until first randomisation prior to run-in with no planned change of the therapy during the trial: anti-hypertensives, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), endothelin receptor antagonists, low dose systemic steroids (e.g. prednisolone ≤10 mg or equivalent). Treatment with a clinically appropriate, stable dose of either Angiotensin-Converting Enzyme Inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) (but not both together), for ≥ 4 weeks prior to visit 1 and until first randomisation with no planned change of the therapy during the trial. In the Investigator's opinion, any kind of diagnosed chronic kidney disease (Diagnosis can be reached by standard clinical method, no biopsy required). Patients with diabetic kidney disease must have type 2 diabetes mellitus and their treatment (including GLP1 receptor agonist) should be unchanged or changes deemed minor (according to investigator's judgement) within 4 weeks prior to Visit 1 and until first randomisation. Glycated Haemoglobin (HbA1c) < 10.0% at Visit 1 measured by the central laboratory. Serum potassium ≤ 4.8 mmol/L at Visit 1 measured by the central laboratory. Seated Systolic Blood Pressure (SBP) ≥ 110 and ≤ 160 mmHg and Diastolic Blood Pressure (DBP) ≥ 65 and ≤ 110 mmHg at Visit 1 (mean values from three Blood Pressure (BP) measurements) and optimised anti-hypertensive treatment according to local standard of care and investigator's judgement. Body Mass Index (BMI) ≥ 18.5 and < 50 kg/m2 at Visit 1. Women of child-bearing potential2 (WOCBP) must be ready and able to use highly effective methods of birth control. Such methods should be used throughout the trial. Men must be vasectomised or willing and able to use a condom if their partner is a WOCBP. Additional inclusion criteria to be assessed before second randomisation (start of Treatment Period): Serum potassium ≤ 4.8 mmol/L measured by local or central laboratory within 7 days prior to randomisation to the Treatment Period. eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) ≥ 20 mL/min/1.73 m2 measured by local or central laboratory within 7 days prior to randomisation to the Treatment Period. Exclusion criteria Treatment with inhibitors of aldosterone mediated effects (e.g., mineralocorticoid receptor antagonists such as spironolactone), or intake of other potassium sparing diuretics (e.g., amiloride) within 7 days prior to first randomisation or planned during trial treatment phase. Treatment with other Renin Angiotensin Aldosterone System (RAAS) interventions (apart from either Angiotensin-Converting Enzyme Inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB)) within 4 weeks prior to Visit 1 and throughout screening or planned during the trial. Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial are also excluded. Type 1 diabetes mellitus, or history of other autoimmune causes of diabetes mellitus (e.g. Latent Autoimmune Diabetes (LADA)) Patients at increased risk of ketoacidosis in the opinion of the investigator. Currently receiving Sodium-glucose cotransporter (SGLT)-2 or SGLT-1/2 inhibitor or planned initiation during the trial. Further criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment period: Empagliflozin + BI 690517<br> | Drug: BI 690517<br>* BI 690517<br>Drug: Empagliflozin<br>* Empagliflozin<br>|
| Experimental: Treatment period: Empagliflozin + Placebo to BI 690517<br> | Drug: Placebo to BI 690517<br>* Placebo to BI 690517<br>Drug: Empagliflozin<br>* Empagliflozin<br>|
| Experimental: Treatment period: Placebo to Empagliflozin + BI 690517<br> | Drug: BI 690517<br>* BI 690517<br>|
| Placebo Comparator: Treatment period: Placebo to Empagliflozin + Placebo to BI 690517<br> | Drug: Placebo to BI 690517<br>* Placebo to BI 690517<br>Drug: Placebo to empagliflozin<br>* Placebo to empagliflozin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from treatment period baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in First Morning Void urine |  | up to 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline |  | up to 14 weeks | 
| UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline |  | up to 14 weeks |