Clinical trial NCT03165240: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetic Nephropathies
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2017-05-24
Enrollment: 62
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 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 \[UACR\].


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).
* 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

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-to-Creatinine Ratio (UACR) measured in morning void urine
timeFrame: Up to 28 days
measure: Change from baseline in log transformed Urine Albumin-to-Creatinine Ratio (UACR) measured in daytime (10-hour) urine
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center Copenhagen
city: Kolding
country: Denmark
facility: Kolding Sygehus
city: København NV
country: Denmark
facility: Bispebjerg og Frederiksberg Hospital
city: København Ø
country: Denmark
facility: Copenhagen University Hospital, Rigshospitalet
city: Angers
country: France
facility: HOP d'Angers
city: La Tronche
country: France
facility: HOP Michallon
city: Paris
country: France
facility: HOP Bichat
city: Poitiers
country: France
facility: HOP la Milétrie
city: Saint-Herblain
country: France
facility: HOP Nord Laënnec
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
city: Essen
country: Germany
facility: InnoDiab Forschung GmbH
city: Gauting
country: Germany
facility: Inamed GmbH
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
city: Ioannina
country: Greece
facility: Univ. Gen. Hosp. of Ioannina
city: P. Faliro
country: Greece
facility: Iatriko of Athens Group/ Iatriko of P. Faliro
city: Psychiko
country: Greece
facility: Iatriko Psychikou
city: Thessaloniki
country: Greece
facility: University General Hospital of Thessaloniki AHEPA
city: Funchal
country: Portugal
facility: Hospital Dr. Nélio Mendonça
city: Lisboa
country: Portugal
facility: APDP - Associação Protectora dos Diabéticos de Portugal
city: Lisboa
country: Portugal
facility: CHULN, EPE - Hospital de Santa Maria
city: Loures
country: Portugal
facility: Hospital Beatriz Ângelo
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário do Porto, EPE - Hospital de Santo António
city: Kemerovo
country: Russian Federation
facility: Res.Inst.-Compl.Iss.Cardi.Dis.
city: Moscow
country: Russian Federation
facility: City Clinical Hospital named after V.P. Demikhova Department of Health of Moscow
city: Moscow
country: Russian Federation
facility: Nonstate Private Healthcare Institution "Scientific Clinical Center of LLC Russian Railways"
city: St. Petersburg
country: Russian Federation
facility: Baltic Med,LLC Clinic BaltMed Ozerki
city: Kosice
country: Slovakia
facility: D & R s.r.o.
city: A Coruña
country: Spain
facility: Hospital A Coruña
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital de Bellvitge
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Göteborg
country: Sweden
facility: CTC Sahlgrenska Universitetssjukhuset
city: Härnösand
country: Sweden
facility: Sjukhuset, Härnösand
city: Uppsala
country: Sweden
facility: CTC Clinical Trial Consultants AB
city: Örebro
country: Sweden
facility: Universitetssjukhuset, Örebro
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
Study officials:
References: