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

Boehringer Ingelheim40 sites in 10 countries62 target enrollmentOctober 5, 2017

ConditionsDiabetic Nephropathies

InterventionsBI 690517 Eplerenone Placebo

DrugsBI 690517 Eplerenone Placebo

Overview

Phase: Phase 1
Intervention: BI 690517
Conditions: Diabetic Nephropathies
Sponsor: Boehringer Ingelheim
Enrollment: 62
Locations: 40
Primary Endpoint: Percentage of patients with drug related Adverse Events (AEs)
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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].

Registry

clinicaltrials.gov

Start Date

October 5, 2017

End Date

May 7, 2020

Last Updated

5 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

Eligibility Criteria

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).

Arms & Interventions

BI 690517 Dose 1

Intervention: BI 690517

BI 690517 Dose 2

Intervention: BI 690517

BI 690517 Dose 3

Intervention: BI 690517

Eplerenone

Intervention: Eplerenone

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Percentage of patients with drug related Adverse Events (AEs)

Time Frame: Up to 35 days

Secondary Outcomes

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)