This Study Tests a New Medicine Called BI 685509 in Patients That Have Kidney Problems Because of Diabetes. The Study Tests How BI 685509 is Taken up in the Body and How Well it is Tolerated (Multiple Rising Doses)

Randomised, Double-blind, Placebo-controlled Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 3 Multiple Rising Oral Doses of BI 685509 Over 28 Days in Male and Female Patients With Diabetic Nephropathy

The main objective of this trial is the safety and tolerability of 3 multiple rising oral doses of BI 685509 over 28 days in male and female patients with Diabetic Nephropathy (DN) as adjunctive to Angiotensin Converting Enzyme inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB). Another objective is the change in Urine Albumin Creatinine Ratio (UACR), an important diagnostic marker of nephropathy.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathies
• Intervention / Treatment: Drug: BI 685509; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bonheiden, Belgium, 2820
    • Bonheiden - HOSP Imelda
  • Brussel, Belgium, 1090
    • Brussels - UNIV UZ Brussel
  • Edegem, Belgium, 2650
    • Edegem - UNIV UZ Antwerpen
  • Gent, Belgium, 9000
    • UNIV UZ Gent
  • Liège, Belgium, 4000
    • Centre hospitalier universitaire de Liege
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
• Czechia
  • Brno, Czechia, 625 00
    • University Hospital Brno
  • Brno, Czechia, 656 91
    • St. Anna Hospital, 2nd Internal Department
  • Prague, Czechia, 10200
    • Quinta Analytica
  • Prague 6, Czechia, 169 00
    • General University Hospital in Prague
  • Praha 4, Czechia, 140 21
    • Institute for Clinical and Experimental Medicine
• Germany
  • Erfurt, Germany, 99084
    • SocraTec R&D GmbH
  • Hamburg, Germany, 20251
    • CTC North GmbH & Co. KG, Hamburg
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Nephrology Consultants, LLC
  • California
    • La Mesa, California, United States, 91942
      • California Institute of Renal Research
    • Los Gatos, California, United States, 95032
      • Office of Dr. Richard S. Cherlin
  • Colorado
    • Denver, Colorado, United States, 80246
      • Creekside Endocrine Associates, PC
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • Fort Lauderdale, Florida, United States, 33312
      • The Center for Diabetes and Endocrine Care
    • Hialeah, Florida, United States, 33012
      • Indago Research and Health Center
    • Lauderdale Lakes, Florida, United States, 33313
      • South Florida Research Institute
    • Miami, Florida, United States, 33014
      • San Marcus Research Clinic, Inc.
    • Miami Springs, Florida, United States, 33166
      • Ocean Blue Medical Research Center, Inc.
    • Tampa, Florida, United States, 33614
      • Genesis Clinical Research
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Boise Kidney and Hypertension Institute
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Research by Design, LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Hospital and Clinic
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology L.L.C.
  • New York
    • Laurelton, New York, United States, 11413
      • Scott Research, Inc.
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington, LLC
  • Tennessee
    • Knoxville, Tennessee, United States, 37923
      • Knoxville Kidney Center PLLC
  • Texas
    • Dallas, Texas, United States, 75231
      • Research Institute Of Dallas
    • Houston, Texas, United States, 77090
      • Houston Clinical Research Associates
    • San Antonio, Texas, United States, 78229
      • Science Advancing Medicine Clinical Research Center
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • York Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Systolic Blood Pressure (SBP) ≥ 110 and ≤ 180 mmHg and Diastolic Blood Pressure (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
• Successful ABPM reading before randomisation, upper arm circumference within the circumference level of the cuff size of either ABPM and/or BP measurement device used in the study

Exclusion Criteria:

• Treatment with SGLT2 inhibitors and/or phosphodiesterase inhibitors, nitrates or riociguat, from screening (Visit 1) or within 5 half-lives before randomisation whatever is earlier.
• Any laboratory value more than 3 times above upper limit of normal (ULN) at screening (Visit 1) or any other laboratory value outside the reference range and clinically relevant (for safe participation) in the investigator judgment
• Confirmed non-diabetic renal disease in the opinion of investigator

• Any other medical condition that in the investigator's opinion poses a safety risk for the patient or may interfere with the study objectives including

  • symptomatic heart failure (NYHA III/IV),
  • known history of tachycardia and/or atrial fibrillation
  • clinically relevant arrhythmias
  • coronary heart disease not compensated by medical treatment (supine pulse rate >70 beats per minute, existing angina pectoris)
  • <6 months after myocardial infarction.
• 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)
• Surgery or trauma with significant blood loss (investigator's judgement) within the last 3 months prior to informed consent or significant blood donation (investigator's judgement) within four weeks prior to first administration of study medication or planned during the trial
• Previous randomization in this trial
• Currently enrolled in another investigational device or drug study, i.e., 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 subject or unlikely to complete the trial
• Women of childbearing potential
• Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Taken orally
Experimental: BI 685509 Dose 1	Drug: BI 685509; Taken orally
Experimental: BI 685509 Dose 2	Drug: BI 685509; Taken orally
Experimental: BI 685509 Dose 3	Drug: BI 685509; Taken orally

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in log transformed Urine albumin creatinine ratio (UACR) measured in morning void urine	Up to 28 days
Change from baseline in log transformed Urine albumin creatinine ratio (UACR) measured in 10-hour urine	Up to 28 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2017
• Primary Completion (Actual): December 10, 2019
• Study Completion (Actual): December 10, 2019

Study Registration Dates

• First Submitted: May 23, 2017
• First Submitted That Met QC Criteria: May 23, 2017
• First Posted (Actual): May 24, 2017

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 8, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: 1366-0004; 2014-004541-27 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No