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

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Diabetic Nephropathies

Treatments: Drug: Placebo; Drug: BI 690517; Drug: Eplerenone

Study type: Interventional

Funder types: Industry

Identifiers

NCT03165240

2017-000563-32 (EudraCT Number)

1378-0008

Details and patient eligibility

About

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].

Enrollment: 62 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

---

62 participants in 5 patient groups, including a placebo group

BI 690517 Dose 1

Experimental group

Treatment:

Drug: BI 690517

BI 690517 Dose 2

Experimental group

Treatment:

Drug: BI 690517

BI 690517 Dose 3

Experimental group

Treatment:

Drug: BI 690517

Eplerenone

Experimental group

Treatment:

Drug: Eplerenone

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo