A Study to Test Whether Different Doses of BI 690517 Alone or in Combination With Empagliflozin Improve Kidney Function in People With Chronic Kidney Disease

Kidney Disease, Chronic Clinical Trial

Official title:

Randomised, Double-blind, Placebo-controlled and Parallel Dose Group Trial to Investigate Efficacy and Safety of Multiple Doses of Oral BI 690517 Over 14 Weeks, Alone and in Combination With Empagliflozin, in Patients With Diabetic and Non-diabetic Chronic Kidney Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05182840
• Other study ID #: 1378.5
• Secondary ID: 2021-001434-1913
• Status: Completed
• Phase: Phase 2
• Start date: January 11, 2022
• Est. completion date: July 10, 2023

Study information

• Verified date: September 2023
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is open to adults with chronic kidney disease. People with and without type 2 diabetes can take part in this study.

The purpose of this study is to find out whether a medicine called BI 690517 improves kidney function in people with chronic kidney disease when taken alone or in combination with a medicine called empagliflozin.

In the first part of the study, participants take empagliflozin or placebo as tablets every day for 2 months. Placebo tablets look like empagliflozin tablets but do not contain any medicine.

In the second part, participants are divided into several groups. Depending on the group, the participants then additionally take different doses of BI 690517 or placebo as tablets for 3.5 months. In this case, placebo tablets look like BI 690517 tablets but do not contain any medicine.

Participants are in the study for about 6 months. During this time, they visit the study site about 12 times. Where possible, about 4 of the 12 visits can be done at the participant's home instead of the study site. The trial staff may also contact the participants by phone or video call.

Participants collect urine samples at home. These samples are then analysed to assess kidney function. At the end of the trial the results are compared between the different groups. The doctors also regularly check participants' health and take note of any unwanted effects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 714
• Est. completion date: July 10, 2023
• Est. primary completion date: June 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria

• Signed and dated written informed consent in accordance with International Council on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.

• Male or female patients of legal adult age (according to local legislation) and aged = 18 years at time of consent.

• estimated Glomerular Filtration Rate (eGFR, Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) = 30 and < 90 mL/min/1.73 m2 at Visit 1 by central laboratory analysis.

• Urine Albumin Creatinine Ratio (UACR) = 200 and < 5,000 mg/g in spot urine (midstream urine sample) by central laboratory analysis at Visit 1.1

• If the patient is taking any of the following medications they should be on a stable dose for at least 4 weeks prior to visit 1 and until first randomisation prior to run-in with no planned change of the therapy during the trial: anti-hypertensives, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), endothelin receptor antagonists, low dose systemic steroids (e.g. prednisolone =10 mg or equivalent).

• Treatment with a clinically appropriate, stable dose of either Angiotensin-Converting Enzyme Inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) (but not both together), for = 4 weeks prior to visit 1 and until first randomisation with no planned change of the therapy during the trial.

• In the Investigator's opinion, any kind of diagnosed chronic kidney disease (Diagnosis can be reached by standard clinical method, no biopsy required). Patients with diabetic kidney disease must have type 2 diabetes mellitus and their treatment (including GLP1 receptor agonist) should be unchanged or changes deemed minor (according to investigator's judgement) within 4 weeks prior to Visit 1 and until first randomisation.

• Glycated Haemoglobin (HbA1c) < 10.0% at Visit 1 measured by the central laboratory.

• Serum potassium = 4.8 mmol/L at Visit 1 measured by the central laboratory.

• Seated Systolic Blood Pressure (SBP) = 110 and = 160 mmHg and Diastolic Blood Pressure (DBP) = 65 and = 110 mmHg at Visit 1 (mean values from three Blood Pressure (BP) measurements) and optimised anti-hypertensive treatment according to local standard of care and investigator's judgement.

• Body Mass Index (BMI) = 18.5 and < 50 kg/m2 at Visit 1.

• Women of child-bearing potential2 (WOCBP) must be ready and able to use highly effective methods of birth control. Such methods should be used throughout the trial. Men must be vasectomised or willing and able to use a condom if their partner is a WOCBP.

Additional inclusion criteria to be assessed before second randomisation (start of Treatment Period):

• Serum potassium = 4.8 mmol/L measured by local or central laboratory within 7 days prior to randomisation to the Treatment Period.

• eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) = 20 mL/min/1.73 m2 measured by local or central laboratory within 7 days prior to randomisation to the Treatment Period.

Exclusion criteria

• Treatment with inhibitors of aldosterone mediated effects (e.g., mineralocorticoid receptor antagonists such as spironolactone), or intake of other potassium sparing diuretics (e.g., amiloride) within 7 days prior to first randomisation or planned during trial treatment phase.

• Treatment with other Renin Angiotensin Aldosterone System (RAAS) interventions (apart from either Angiotensin-Converting Enzyme Inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB)) within 4 weeks prior to Visit 1 and throughout screening or planned during the trial. Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial are also excluded.

• Type 1 diabetes mellitus, or history of other autoimmune causes of diabetes mellitus (e.g. Latent Autoimmune Diabetes (LADA))

• Patients at increased risk of ketoacidosis in the opinion of the investigator.

• Currently receiving Sodium-glucose cotransporter (SGLT)-2 or SGLT-1/2 inhibitor or planned initiation during the trial.

Further criteria apply.

Related Conditions & MeSH terms

• Kidney Disease, Chronic
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• BI 690517
BI 690517
• Placebo to BI 690517
Placebo to BI 690517
• Empagliflozin
Empagliflozin
• Placebo to empagliflozin
Placebo to empagliflozin

Locations

Country	Name	City	State
Argentina	CIMEL centro de Investigaciones Médicas Lanús	Buenos Aires
Argentina	CEDIC - Centro de Investigacion Clinica	Caba
Argentina	Glenny Corp. S.A. Bioclinica Argentina	Ciudad Autonoma Buenos Aires
Argentina	Instituto Privado de Investigaciones Clínica Córdoba S.A.	Cordoba
Argentina	Centro de Salud Renal Junín	Junín
Argentina	Centro de Investigaciones Médicas Mar del Plata	Mar del Plata
Argentina	Instituto Médico Catamarca - IMEC	Rosario
Argentina	CEMEDIC - Centro de Especialidades Medicas	Villa Luro
Australia	Monash University	Box Hill	Victoria
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Belgium	Brussels - UNIV UZ Brussel	Brussel
Belgium	Brussels - UNIV Saint-Luc	Bruxelles
Belgium	La Louvière - UNIV CHU Tivoli	La Louvière
Belgium	UZ Leuven	Leuven
Belgium	Charleroi - UNIV CHU de Charleroi	Lodelinsart
Brazil	Hospital Universitário João de Barros Barreto	Belém
Brazil	Faculdade de Medicina de Botucatu - UNESP	Botucatu
Brazil	Fundação Pró Renal Brasil	Curitiba
Brazil	Universidade Federal do Rio Grande do Sul	Porto Alegre
Brazil	Ruschel Medicina e Pesquisa Clínica	Rio de Janeiro
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clínicos	São Bernardo do Campo
Brazil	BR Trials	Sao Paulo
Brazil	Centro de Pesquisa Clinica - CPCLIN	Sao Paulo
Brazil	Hospital do RIM - UNIFESP	São Paulo
Bulgaria	Medical Center Rusemed	Ruse
Bulgaria	Medical Center Synexus Sofia EOOD	Sofia
Bulgaria	Robert Koch Clinic Sofia	Sofia
Bulgaria	MHAT Prof Stoyan Kirkovich AD	Stara Zagora
Canada	LMC Clinical Research Inc. (Brampton)	Brampton	Ontario
Canada	Recherche GCP Research	Montreal	Quebec
Canada	The Bailey Clinic	Red Deer	Alberta
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Sameh Fikry Medicine Professional Corporation	Waterloo	Ontario
Canada	Shivinder Jolly, Nephrologist	Waterloo	Ontario
China	Guangdong Provincial People's Hospital	Guangzhou
China	The First Afiliated Hospital, Sun Yet-sen University	Guangzhou
China	Zhejiang Province People's Hospital	Hangzhou
China	The First People's Hospital of Nanning	Nanning
China	Huashan Hospital, Fudan University	Shanghai
China	Shanghai Fifth People's Hospital affiliated to Fudan University	Shanghai
Czechia	DIKa centrum s.r.o.	Havirov
Czechia	Synexus Czech s.r.o.	Prague
Czechia	MILAN KVAPIL s.r.o.	Pribram
Czechia	Hospital Slany, Internal Department	Slany
Finland	Satucon Oy	Kuopio
Finland	Tampere University Hospital	Tampere
Finland	Turku University Hospital / TYKS	Turku
Germany	Herz- und Diabeteszentrum Nordrhein-Westfalen, Bad Oeynhausen	Bad Oeynhausen
Germany	Institut für klinische Forschung und Entwicklung (IKFE) Berlin GmbH	Berlin
Germany	Cardiologicum Dresden und Pirna	Dresden
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	DaVita Clinical Research Germany GmbH	Düsseldorf
Germany	Synexus Clinical Research GmbH	Frankfurt
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Synexus Clinical Research GmbH	Leipzig
Germany	Universitätsklinikum Würzburg AÖR	Würzburg
Greece	"Attiko" Hospital of Athens	Athens
Greece	General Hospital of Athens "Laiko"	Athens
Greece	Univ. Gen. Hosp. of Ioannina	Ioannina
Greece	Iatriko of Athens Group/ Iatriko of P. Faliro	P. Faliro
Hong Kong	Prince of Wales Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Hungary	Lausmed Kft. Outpatient Unit of Internal Medicine	Baja
Hungary	DRC Drug Research Ltd	Balatonfured
Hungary	Semmelweis University	Budapest
Hungary	Synexus Hungary Healthcare Service Ltd.	Budapest
Hungary	University Debrecen Hospital	Debrecen
Hungary	Markhot Ferenc Hospital, Eger	Eger
Hungary	BKS Research Ltd	Hatvan
India	Government Medical College & Hospital	Aurangabad
India	Jaipur National University Institute for Medical Science & Research Centre	Jaipur
India	SMS Medical College and HospitaL	Jaipur
India	Ganesh Shankar Vidyarthi Memorial Medical College	Kanpur
India	K R Hospital Mysore Medical College and Research Centre	Mysore
India	Kingsway Hospitals	Nagpur
India	All India Institute of Medical Sciences	New Delhi
India	Shree Giriraj Multispeciality Hospital	Rajkot
India	Galaxy Lifecare Services Pvt. Ltd.	Varanasi
India	Christian Medical College	Vellore
Italy	A.O. Policlinico Giovanni XXIII di Bari	Bari
Italy	ASST Papa Giovanni XXIII - A.O. Papa Giovanni XXIII	Bergamo
Japan	Daiyukai Clinic	Aichi, Ichinomiya
Japan	Meitetsu Hospital	Aichi, Nagoya
Japan	Nagoya Kyoritsu Hospital	Aichi, Nagoya
Japan	TOSAKI Clinic for Diabetes and Endocrinology	Aichi, Nagoya
Japan	National Hospital Organization Takasaki General Medical Center	Gumma, Takasaki
Japan	Kyoto Okamoto Memorial Hospital	Kyoto, Kuse-gun
Japan	Ina Central Hospital	Nagano, Ina
Japan	Suwa Red Cross Hospital	Nagano, Suwa
Japan	Asano Clinic	Saitama, Kawagoe
Japan	Omihachiman Community Medical Center	Shiga, Omihachiman
Japan	The University of Tokyo Hospital	Tokyo, Bunkyo-ku
Japan	Tokyo Medical University Hachioji Medical Center	Tokyo, Hachioji
Japan	Miho Clinic	Tokyo, Shinagawa-ku
Japan	Yamaura Medical Clinic	Ueda, Nagano
Korea, Republic of	Korea University Ansan Hospital	Ansan
Korea, Republic of	Chungbuk National University Hospital	Cheongiu
Korea, Republic of	Inje University Ilsan Paik Hospital	Goyang
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Malaysia	Hospital Selayang	Batu Caves
Malaysia	University Kebangsaan Malaysia	Cheras, Kuala Lumpur
Malaysia	Klinik Kesihatan Mahmoodiah	Johor Bahru
Malaysia	Tuanku Fauziah Hospital	Kangar
Malaysia	Hospital Raja Perempuan Zainab II, Kota Bharu	Kota Bharu
Malaysia	Hospital Seri Manjung	Seri Manjung
Mexico	Centro de Investigacion Cardiometabolica de Aguascalientes	Aguascalientes
Mexico	Unidad de Investigación Clinica y Atencion Medica HEPA SC	Guadalajara
Mexico	Centro Mexicano de Desarrollo de Estudios Clínicos SA -CEMDEC	Mexico
Mexico	Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.	Mexico
Mexico	CEDOPEC-Ctro Esp en Diab, Obesidad y Prev de Enf Cardiovasc	México
Mexico	Clinstile S.A. de C.V.	México
Mexico	Hospital Universitario Dr Jose Eleuterio Gonzalez	Nuevo León
Norway	Akershus Universitetssykehus HF	Nordbyhagen
Norway	Helse Stavanger, Stavanger Universitetssykehus	Stavanger
Philippines	Norzel Medical and Diagnostic Clinic	Cebu City
Philippines	Davao Doctors Hospital	Davao City
Philippines	West Visayas State University Medical Center	Iloilo City
Philippines	Institute for Studies on Diabetes Foundation Inc.	Marikina city
Philippines	The Medical City	Pasig City
Philippines	Philippine Heart Center	Quezon City
Philippines	Senor Santo Nino Hospital	Tarlac
Poland	INTERCORE Medical Center	Bydgoszcz
Poland	Synexus Polska SCM Sp. z o.o. Gdansku, Gdansk	Gdansk
Poland	Pro Familia Altera	Katowice
Poland	Synexus Polska Sp. z o.o. Oddzial w Katowicach, Katowice	Katowice
Poland	Synexus Lodz Medical Center	Lodz
Poland	Clinical Best Solutions	Lublin
Poland	NZOZ Specialized Ambulance "MEDICA"	Lublin
Poland	Hospitals of Tczew S.A.	Pomorskie
Poland	Independent Health Care Center HCP Medical Center	Poznan
Poland	Omedica Medical Centre, Poznan	Poznan
Poland	Synexus Poland, Branch in Poznan	Poznan
Poland	Barwijuk Clinics	Warszawa
Poland	Centrum Medyczne Synexus	Warszawa
Poland	Synexus Poland, Branch in Wroclaw	Wroclaw
Portugal	Hospital Garcia de Orta, EPE	Almada
Portugal	Centro Hospitalar do Baixo Vouga - Hospital Infante Dom Pedro	Aveiro
Portugal	CHLO, EPE - Hospital de Santa Cruz	Carnaxide
Portugal	Centro Hosp. de Leiria-Pombal	Leiria
Portugal	APDP - Associação Protectora dos Diabéticos de Portugal	Lisboa
Portugal	Centro Hospitalar de Vila Nova de Gaia	Vila Nova de Gaia
South Africa	Iatros International	Bloemfontein
South Africa	Langeberg Clinical Trials	Cape Town
South Africa	Paarl Research Centre	Cape Town
South Africa	Synexus Helderberg Clinical Research Centre	Cape Town
South Africa	TREAD Research	Cape Town
South Africa	Latiff, GHVM	Durban
South Africa	DJW Navorsing	Krugersdorp
South Africa	Synexus Watermeyer Clinical Research Centre	Pretoria
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Público Da Mariña	Burela
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda
Sweden	Centralsjukhuset, Kristianstad	Kristianstad
Sweden	Universitetssjukhuset, Linköping	Linköping
Sweden	Citydiabetes, Stockholm	Stockholm
Switzerland	University Hospital of Lausanne	Lausanne
Turkey	Istanbul University	Istanbul
United States	New Mexico Clinical Research and Osteoporosis Center, Inc.	Albuquerque	New Mexico
United States	Triad Internal Medicine	Asheboro	North Carolina
United States	Heritage Valley Medical Group	Beaver	Pennsylvania
United States	Clinical Research of Brandon LLC	Brandon	Florida
United States	Diabetes & Endocrinology Associates of Stark County	Canton	Ohio
United States	Clearview Medical Research, LLC	Canyon Country	California
United States	Cedar Crosse Research Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Horizon Research Group	Coral Gables	Florida
United States	Research Institute of Dallas	Dallas	Texas
United States	Colorado Kidney Care	Denver	Colorado
United States	Academy Of Diabetes, Thyroid And Endocrine, PA	El Paso	Texas
United States	Aa Mrc Llc	Flint	Michigan
United States	Elite Research Center, LLC	Flint	Michigan
United States	Elixia Fort Lauderdale, LLC	Fort Lauderdale	Florida
United States	PrimeCare Medical Group	Houston	Texas
United States	Clinical Research Consultants, LLC	Kansas City	Missouri
United States	Knoxville Kidney Center PLLC	Knoxville	Tennessee
United States	Forte Family Practice	Las Vegas	Nevada
United States	South Florida Research Institute	Lauderdale Lakes	Florida
United States	Pacific Renal Associates	Long Beach	California
United States	P&I Clinical Research, LLC	Lufkin	Texas
United States	Aventiv Research Inc.	Mesa	Arizona
United States	Horizon Research Group, LLC	Miami	Florida
United States	San Marcus Research Clinic, Inc.	Miami	Florida
United States	Total Research Group, LLC	Miami	Florida
United States	Lucas Research, Inc.	Morehead City	North Carolina
United States	Boise Kidney and Hypertension PLLC	Nampa	Idaho
United States	Amicis Research Center	Northridge	California
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	West Orange Endocrinology	Ocoee	Florida
United States	Pines Care Research Center	Pembroke Pines	Florida
United States	AKDHC Medical Research Services, LLC	Phoenix	Arizona
United States	Monument Health	Rapid City	South Dakota
United States	California Kidney Specialists	San Dimas	California
United States	Providence Medical Research Center	Spokane	Washington
United States	Simcare Medical Research, LLC	Sugar Land	Texas
United States	Universal Research Group, LLC	Tacoma	Washington
United States	Elixia Tampa, LLC	Temple Terrace	Florida
United States	Elixia Upland, LLC	Upland	Pennsylvania
United States	Kansas Nephrology Research Institute, LLC	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  Finland,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Norway,  Philippines,  Poland,  Portugal,  South Africa,  Spain,  Sweden,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from treatment period baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in First Morning Void urine		up to 14 weeks
Secondary	UACR response I, defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline		up to 14 weeks
Secondary	UACR response II, defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline		up to 14 weeks

External Links

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