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

Diabetic Nephropathies Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03165240
• Other study ID #: 1378-0008
• Secondary ID: 2017-000563-32
• Status: Completed
• Phase: Phase 1
• Start date: October 5, 2017
• Est. completion date: May 7, 2020

Study information

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

Clinical Trial 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].

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: May 7, 2020
• Est. primary completion date: April 16, 2020
• 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 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

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Kidney Diseases

Intervention

Drug:
• BI 690517
Film-coated tablet
• Eplerenone
Film-coated tablet
• Placebo
Film-coated tablet

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center Copenhagen	Gentofte
Denmark	Bispebjerg og Frederiksberg Hospital	København NV
Denmark	Copenhagen University Hospital, Rigshospitalet	København Ø
Denmark	Kolding Sygehus	Kolding
France	HOP d'Angers	Angers
France	HOP Michallon	La Tronche
France	HOP Bichat	Paris
France	HOP la Milétrie	Poitiers
France	HOP Nord Laënnec	Saint-Herblain
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	InnoDiab Forschung GmbH	Essen
Germany	Inamed GmbH	Gauting
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Profil Institut für Stoffwechselforschung GmbH	Neuss
Greece	Univ. Gen. Hosp. of Ioannina	Ioannina
Greece	Iatriko of Athens Group/ Iatriko of P. Faliro	P. Faliro
Greece	Iatriko Psychikou	Psychiko
Greece	University General Hospital of Thessaloniki AHEPA	Thessaloniki
Portugal	Hospital Dr. Nélio Mendonça	Funchal
Portugal	APDP - Associação Protectora dos Diabéticos de Portugal	Lisboa
Portugal	CHULN, EPE - Hospital de Santa Maria	Lisboa
Portugal	Hospital Beatriz Ângelo	Loures
Portugal	Centro Hospitalar Universitário do Porto, EPE - Hospital de Santo António	Porto
Russian Federation	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	Nonstate Private Healthcare Institution "Scientific Clinical Center of LLC Russian Railways"	Moscow
Russian Federation	Baltic Med,LLC Clinic BaltMed Ozerki	St. Petersburg
Slovakia	D & R s.r.o.	Kosice
Spain	Hospital A Coruña	A Coruña
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital de Bellvitge	L'Hospitalet de Llobregat
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda
Spain	Hospital Virgen Macarena	Sevilla
Spain	Hospital Clínico de Valencia	Valencia
Sweden	CTC Sahlgrenska Universitetssjukhuset	Göteborg
Sweden	Sjukhuset, Härnösand	Härnösand
Sweden	Universitetssjukhuset, Örebro	Örebro
Sweden	CTC Clinical Trial Consultants AB	Uppsala
United Kingdom	University Hospital of Wales	Cardiff

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Denmark,  France,  Germany,  Greece,  Portugal,  Russian Federation,  Slovakia,  Spain,  Sweden,  United Kingdom, 

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-to-Creatinine Ratio (UACR) measured in morning void urine		Up to 28 days
Secondary	Change from baseline in log transformed Urine Albumin-to-Creatinine Ratio (UACR) measured in daytime (10-hour) urine		Up to 28 days