This International Study Tests BI 690517 in Patients With Diabetic Kidney Disease. The Study Tests How 3 Different Doses of BI 690517 Are Taken up in the Body and How Well They Are Tolerated

Study Overview
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Brief Summary
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The primary objective of this current trial is to investigate the safety and tolerability of 3 oral doses of BI 690517 over 28 days in female and male patients with diabetic nephropathy as add-on-therapy to Angiotensin Converting Enzyme inhibitor [ACEi] or Angiotensin-receptor blockers [ARB]. Secondary objective is to evaluate the change from baseline in Urine Albumin-to-Creatinine Ratio [UACR].

Official Title
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Randomised, Double-blind, Placebo-controlled (Within Dose Groups) and Active Controlled (Eplerenone Group) Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 3 Oral Doses of BI 690517 Over 28 Days in Female and Male Patients With Diabetic Nephropathy

Conditions
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Diabetic Nephropathies

Intervention / Treatment
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* Drug: BI 690517
* Drug: Eplerenone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. Male or postmenopausal (last menstruation ≥ 2 years ago) patients, or female patients who are sterilized by either hysterectomy, bilateral salpingectomy and/or bilateral oophorectomy. Male patients with partners of child-bearing potential must be willing to use condoms from the time of the first intake of study drug until follow-up. eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) ≥ 20 and < 75 ml/min/1.73 m2 at Visit 1 measured by the central laboratory and no planned start of renal replacement therapy during the trial. UACR ≥ 200 and <3500 mg/g in spot urine (midstream urine sample) at Visit 1 measured by the central laboratory. Treatment with either ACEi or ARB, stable dose since ≥ 4 weeks before Visit 1 with no planned change of the therapy. Patients with type 1 or type 2 diabetes mellitus, diagnosed before informed consent and treated with insulin, glucagon-like peptide (GLP) 1 agonists and/or oral antidiabetic medication. Treatment should have been unchanged (investigator's judgment) within 4 weeks before Visit 1 and until randomisation. Glycated Haemoglobin (HbA1c) < 10.0% at Visit 1 measured by the central laboratory. Seated SBP ≥ 110 and ≤ 180 mmHg and DBP ≥ 70 and ≤ 110 mmHg at Visit 1 Age at screening ≥ 18 years for male and permanently sterilized female patients and ≥ 45 years for postmenopausal female patients. Body Mass Index (BMI) ≥ 18.5 and < 45 kg/m2. Exclusion Criteria: Treatment with with SGLT2 inhibitors and/or inhibitors of aldosterone mediated effects like mineralocorticoid receptor antagonists at visit 1 and thereafter. Intake of potassium sparing diuretics like amiloride or potassium supplements during the study (this period starts at Visit 1). At Visit 1 cortisol peak level 30 minutes (± 5 min) after iv injection of Adrenocorticotropic hormone (ACTH) is an increase by less than 200 nmol/l compared to pre-ACTH injection. Dual or triple blockade of the Renin Angiotensin System (RAS) (e.g. ACEi + ARB; ACEi + renin inhibitor; or ARB + renin inhibitor; or ACEi + ARB + renin inhibitor) 12 weeks before Visit 1 and for the duration of study. History of non-diabetic renal disease according to investigator's opinion and/or renal transplant recipients. Hyperkalaemia (K+ > 5.0 mmol/L) at visit 1 and until start of treatment measured by any local or central lab. Clinical signs of acute or chronic urinary tract infection 14 days before randomization (based on investigator's judgement). Acute febrile diseases 14 days before randomisation (based on investigator´s judgement). Heart failure, patients with NYHA III / IV. Surgery or trauma with significant blood loss or blood donation within 12 weeks prior to first administration of study medication (based on investigator´s judgement) or planned surgeries during the trial e.g. hip replacement (based on investigator's judgement). Any other medical condition that in the investigator's opinion poses a safety risk for the patient or may interfere with the study objectives. Any laboratory value more than 3 times above upper limit normal (ULN) at screening (visit 1) or any other laboratory value outside the reference range and clinically relevant in the investigator's judgment. Medical history of cancer or treatment for cancer in the last two years prior to Visit 1 (except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix, and prostatic cancer of low grade [T1 or T2] is exempted). Previous enrolment in this trial. Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational treatment(s). Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable study patient or unlikely to complete the trial. Women of childbearing potential Further exclusion 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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 690517 Dose 1<br> | Drug: BI 690517<br>* Film-coated tablet<br>|
| Experimental: BI 690517 Dose 2<br> | Drug: BI 690517<br>* Film-coated tablet<br>|
| Experimental: BI 690517 Dose 3<br> | Drug: BI 690517<br>* Film-coated tablet<br>|
| Experimental: Eplerenone<br> | Drug: Eplerenone<br>* Film-coated tablet<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Film-coated tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with drug related Adverse Events (AEs) |  | Up to 35 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in log transformed Urine Albumin-to-Creatinine Ratio (UACR) measured in morning void urine |  | Up to 28 days | 
| Change from baseline in log transformed Urine Albumin-to-Creatinine Ratio (UACR) measured in daytime (10-hour) urine |  | Up to 28 days |