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)

Diabetic Nephropathies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03165227
• Other study ID #: 1366-0004
• Secondary ID: 2014-004541-27
• Status: Completed
• Phase: Phase 1
• Start date: October 17, 2017
• Est. completion date: December 10, 2019

Study information

• Verified date: January 2020
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: December 10, 2019
• Est. primary completion date: December 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Kidney Diseases

Intervention

Drug:
• BI 685509
Taken orally
• Placebo
Taken orally

Locations

Country	Name	City	State
Belgium	Bonheiden - HOSP Imelda	Bonheiden
Belgium	Brussels - UNIV UZ Brussel	Brussel
Belgium	Edegem - UNIV UZ Antwerpen	Edegem
Belgium	UNIV UZ Gent	Gent
Belgium	Centre Hospitalier Universitaire de Liège	Liège
Canada	Toronto General Hospital	Toronto	Ontario
Czechia	St. Anna Hospital, 2nd Internal Department	Brno
Czechia	University Hospital Brno	Brno
Czechia	Quinta Analytica	Prague
Czechia	General University Hospital in Prague	Prague 6
Czechia	Institute for Clinical and Experimental Medicine	Praha 4
Germany	SocraTec R&D GmbH	Erfurt
Germany	CTC North GmbH & Co. KG, Hamburg	Hamburg
United States	Research by Design, LLC	Chicago	Illinois
United States	Innovative Research of West Florida, Inc.	Clearwater	Florida
United States	Research Institute of Dallas	Dallas	Texas
United States	Creekside Endocrine Associates, PC	Denver	Colorado
United States	The Center for Diabetes and Endocrine Care	Fort Lauderdale	Florida
United States	Indago Research and Health Center	Hialeah	Florida
United States	Houston Clinical Research Associates	Houston	Texas
United States	Nephrology Consultants, LLC	Huntsville	Alabama
United States	Knoxville Kidney Center PLLC	Knoxville	Tennessee
United States	California Institute of Renal Research	La Mesa	California
United States	South Florida Research Institute	Lauderdale Lakes	Florida
United States	Scott Research, Inc.	Laurelton	New York
United States	Office of Dr. Richard S. Cherlin	Los Gatos	California
United States	Boise Kidney and Hypertension Institute	Meridian	Idaho
United States	San Marcus Research Clinic, Inc.	Miami	Florida
United States	Ocean Blue Medical Research Center, Inc.	Miami Springs	Florida
United States	Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	York Clinical Research, LLC	Norfolk	Virginia
United States	Science Advancing Medicine Clinical Research Center	San Antonio	Texas
United States	Northwest Louisiana Nephrology L.L.C.	Shreveport	Louisiana
United States	Genesis Clinical Research	Tampa	Florida
United States	PMG Research of Wilmington, LLC	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with drug related Adverse Events (AEs)		Up to 35 days
Secondary	Change from baseline in log transformed Urine albumin creatinine ratio (UACR) measured in morning void urine		Up to 28 days
Secondary	Change from baseline in log transformed Urine albumin creatinine ratio (UACR) measured in 10-hour urine		Up to 28 days