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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

Phase 1
Completed
Conditions
Diabetic Nephropathies
Interventions
Drug: BI 690517
Drug: Eplerenone
Drug: Placebo
Registration Number
NCT03165240
Lead Sponsor
Boehringer Ingelheim
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 \[UACR\].

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
62
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.
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
BI 690517 Dose 1BI 690517-
BI 690517 Dose 2BI 690517-
BI 690517 Dose 3BI 690517-
EplerenoneEplerenone-
PlaceboPlacebo-
Primary Outcome Measures
NameTimeMethod
Percentage of patients with drug related Adverse Events (AEs)Up to 35 days
Secondary Outcome Measures
NameTimeMethod
Change from baseline in log transformed Urine Albumin-to-Creatinine Ratio (UACR) measured in morning void urineUp to 28 days
Change from baseline in log transformed Urine Albumin-to-Creatinine Ratio (UACR) measured in daytime (10-hour) urineUp to 28 days

Trial Locations

Locations (40)

Steno Diabetes Center Copenhagen

🇩🇰

Gentofte, Denmark

Bispebjerg og Frederiksberg Hospital

🇩🇰

København NV, Denmark

Copenhagen University Hospital, Rigshospitalet

🇩🇰

København Ø, Denmark

HOP d'Angers

🇫🇷

Angers, France

Hospital Dr. Nélio Mendonça

🇵🇹

Funchal, Portugal

University General Hospital of Thessaloniki AHEPA

🇬🇷

Thessaloniki, Greece

Iatriko Psychikou

🇬🇷

Psychiko, Greece

Inamed GmbH

🇩🇪

Gauting, Germany

HOP la Milétrie

🇫🇷

Poitiers, France

InnoDiab Forschung GmbH

🇩🇪

Essen, Germany

APDP - Associação Protectora dos Diabéticos de Portugal

🇵🇹

Lisboa, Portugal

Iatriko of Athens Group/ Iatriko of P. Faliro

🇬🇷

P. Faliro, Greece

Profil Institut für Stoffwechselforschung GmbH

🇩🇪

Neuss, Germany

Univ. Gen. Hosp. of Ioannina

🇬🇷

Ioannina, Greece

Centro Hospitalar Universitário do Porto, EPE - Hospital de Santo António

🇵🇹

Porto, Portugal

Hospital Puerta de Hierro

🇪🇸

Majadahonda, Spain

Hospital A Coruña

🇪🇸

A Coruña, Spain

University Hospital of Wales

🇬🇧

Cardiff, United Kingdom

Hospital Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital Beatriz Ângelo

🇵🇹

Loures, Portugal

D & R s.r.o.

🇸🇰

Kosice, Slovakia

Nonstate Private Healthcare Institution "Scientific Clinical Center of LLC Russian Railways"

🇷🇺

Moscow, Russian Federation

Baltic Med,LLC Clinic BaltMed Ozerki

🇷🇺

St. Petersburg, Russian Federation

Sjukhuset, Härnösand

🇸🇪

Härnösand, Sweden

CTC Clinical Trial Consultants AB

🇸🇪

Uppsala, Sweden

Hospital Virgen Macarena

🇪🇸

Sevilla, Spain

HOP Bichat

🇫🇷

Paris, France

HOP Michallon

🇫🇷

La Tronche, France

HOP Nord Laënnec

🇫🇷

Saint-Herblain, France

Medizinische Hochschule Hannover

🇩🇪

Hannover, Germany

Kolding Sygehus

🇩🇰

Kolding, Denmark

Universitätsklinikum Carl Gustav Carus Dresden

🇩🇪

Dresden, Germany

CHULN, EPE - Hospital de Santa Maria

🇵🇹

Lisboa, Portugal

Res.Inst.-Compl.Iss.Cardi.Dis.

🇷🇺

Kemerovo, Russian Federation

City Clinical Hospital named after V.P. Demikhova Department of Health of Moscow

🇷🇺

Moscow, Russian Federation

Universitetssjukhuset, Örebro

🇸🇪

Örebro, Sweden

Hospital de Bellvitge

🇪🇸

L'Hospitalet de Llobregat, Spain

Hospital General Universitario Gregorio Marañón

🇪🇸

Madrid, Spain

CTC Sahlgrenska Universitetssjukhuset

🇸🇪

Göteborg, Sweden

Hospital Clínico de Valencia

🇪🇸

Valencia, Spain

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