Clinical trial NCT03165227: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetic Nephropathies
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2017-05-24
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


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 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

Primary outcomes:
measure: Percentage of patients with drug related Adverse Events (AEs)
timeFrame: Up to 35 days
Secondary outcomes:
measure: Change from baseline in log transformed Urine albumin creatinine ratio (UACR) measured in morning void urine
timeFrame: Up to 28 days
measure: Change from baseline in log transformed Urine albumin creatinine ratio (UACR) measured in 10-hour urine
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Nephrology Consultants, LLC
state: Alabama
city: La Mesa
country: United States
facility: California Institute of Renal Research
state: California
city: Los Gatos
country: United States
facility: Office of Dr. Richard S. Cherlin
state: California
city: Denver
country: United States
facility: Creekside Endocrine Associates, PC
state: Colorado
city: Clearwater
country: United States
facility: Innovative Research of West Florida, Inc.
state: Florida
city: Fort Lauderdale
country: United States
facility: The Center for Diabetes and Endocrine Care
state: Florida
city: Hialeah
country: United States
facility: Indago Research and Health Center
state: Florida
city: Lauderdale Lakes
country: United States
facility: South Florida Research Institute
state: Florida
city: Miami Springs
country: United States
facility: Ocean Blue Medical Research Center, Inc.
state: Florida
city: Miami
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Tampa
country: United States
facility: Genesis Clinical Research
state: Florida
city: Meridian
country: United States
facility: Boise Kidney and Hypertension Institute
state: Idaho
city: Chicago
country: United States
facility: Research by Design, LLC
state: Illinois
city: New Orleans
country: United States
facility: Tulane University Hospital and Clinic
state: Louisiana
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology L.L.C.
state: Louisiana
city: Laurelton
country: United States
facility: Scott Research, Inc.
state: New York
city: Wilmington
country: United States
facility: PMG Research of Wilmington, LLC
state: North Carolina
city: Knoxville
country: United States
facility: Knoxville Kidney Center PLLC
state: Tennessee
city: Dallas
country: United States
facility: Research Institute of Dallas
state: Texas
city: Houston
country: United States
facility: Houston Clinical Research Associates
state: Texas
city: San Antonio
country: United States
facility: Science Advancing Medicine Clinical Research Center
state: Texas
city: Norfolk
country: United States
facility: York Clinical Research, LLC
state: Virginia
city: Bonheiden
country: Belgium
facility: Bonheiden - HOSP Imelda
city: Brussel
country: Belgium
facility: Brussels - UNIV UZ Brussel
city: Edegem
country: Belgium
facility: Edegem - UNIV UZ Antwerpen
city: Gent
country: Belgium
facility: UNIV UZ Gent
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Brno
country: Czechia
facility: University Hospital Brno
city: Brno
country: Czechia
facility: St. Anna Hospital, 2nd Internal Department
city: Prague 6
country: Czechia
facility: General University Hospital in Prague
city: Prague
country: Czechia
facility: Quinta Analytica
city: Praha 4
country: Czechia
facility: Institute for Clinical and Experimental Medicine
city: Erfurt
country: Germany
facility: SocraTec R&D GmbH
city: Hamburg
country: Germany
facility: CTC North GmbH & Co. KG, Hamburg
Study officials:
References: