Diabetic Nephropathies
Conditions
Brief summary
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 \[UACR\].
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of patients with drug related Adverse Events (AEs) | Up to 35 days |
Secondary
| Measure | 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 |
Countries
Denmark, France, Germany, Greece, Portugal, Russia, Slovakia, Spain, Sweden, United Kingdom
Outcome results
None listed