Study on the Safety of the Drug Runcaciguat and How Well it Works When Given at the Highest Dose as Tolerated by Individual Patient Whose Kidneys Are Not Working Properly and Suffering at the Same Time From High Blood Sugar and/or High Blood Pressure and a Disease of the Heart and the Blood Vessels.
- Registration Number
- NCT04507061
- Lead Sponsor
- Bayer
- Brief Summary
Researchers in this study want to learn more about the safety of the drug runcaciguat and how well it works when given at the highest dose as tolerated by the individual patient whose kidneys are not working properly and suffering at the same time from high blood sugar and/or high blood pressure and a disease of the heart and the blood vessels. Runcaciguat is a new drug under development for the improvement of kidney function. It works by activating proteins that helps to dilate blood vessels, including vessels in the kidneys. This can improve blood flow in kidney and may slow down the progression of kidney disease. This dilative effect can also influence the heart rate and blood pressure. Researchers also wants to find the best dose of the drug during the study.
Participants in this study will receive either runcaciguat or placebo tablets every morning for 8 weeks. A placebo looks like the study drug but does not have any active medicine in it. On a weekly basis, the dose of the runcaciguat will be increased step by step. In total, participants will visit the doctors about 10 times, and the observation will last for about 16 weeks. Blood and urine samples will collected from the participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 243
Age - Participant must be ≥ 45 of age inclusive, at the time of signing the informed consent.
Type of Participant and Disease Characteristics
- Participants who have:
-
history of any of the following:
- type 2 diabetes mellitus as defined by the American Diabetes Association (on treatment with glucose-lowering medications and/or insulin) for at least 2 years, and/or;
- diagnosis of hypertension (defined as systolic blood pressure [BP] values ≥ 140 mmHg and/or diastolic BP values ≥90 mmHg) and on hypertension medication for at least 5 years;
-
established atherosclerotic cardiovascular disease (e.g. coronary artery disease, peripheral arterial disease, cerebrovascular disease) or heart failure;
-
a clinical diagnosis of chronic kidney disease (CKD) based on all of the following criteria:
- (estimated) glomerular filtration rate (eGFR) ≥ 25 mL/min/1.73 m^2 but ≤ 60 mL/min/1.73 m^2 (acc. Percentage of decrease in eGFR [CKD EPI]);
- persistent high albuminuria defined as urine albumin-to-creatinine ratio [UACR] of between 30 mg/g and 3000 mg/g in 2 first morning void samples (collected at least 1 week apart);
- Stable treatment with angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) for the participant maximum tolerated labelled daily dose and otherwise stable antihypertensive treatment both for at least 3 months before randomization, without any adjustments to this therapy for at least 4 weeks prior to randomization;
-
Diabetes patients that are on SGLT2-inhibitor (SGLT: sodium glucose transport protein) have to be on stable treatment for at least 3 months before Screening visit.
-
Known non-diabetic and non-hypertension related renal diseases as autosomal dominant polycystic kidney disease, bilateral clinically relevant renal artery stenosis, lupus nephritis, or ANCA-associated vasculitis, IgA nephropathy without hypertension, or any other secondary glomerulonephritis;
-
Clinical diagnoses of heart failure and persistent symptoms (New York Heart Association (NYHA class III - IV);
-
Uncontrolled hypertension indicated by >160 mmHg systolic BP or ≥ 100 mmHg diastolic BP;
-
History of secondary hypertension (i.e., renal artery stenosis, primary aldosteronism, or pheochromocytoma);
-
Stroke, transient ischemic cerebral attack, acute coronary syndrome, or hospitalization for worsening heart failure, in the last 3 months prior to the planned randomization;
-
Dialysis for acute renal failure within the previous 6 months prior to the planned randomization;
-
Renal allograft in place or a scheduled kidney transplant within the next 18 weeks (being on a waiting list does not exclude the subject);
-
Hepatic insufficiency classified as Child-Pugh B or C or other significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis as indicated by e.g. aspartate aminotransferase [AST] or Alanine aminotransferase [ALT] >3x upper limit of norm [ULN]);
-
Active malignancy other than treated squamous cell, carcinoma in situ, or basal cell carcinoma of the skin Prior/Concomitant Therapy;
-
Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study including but not limited to:
- History of active inflammatory bowel disease within the last 6 months before randomization;
- Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
- Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last 6 months before randomization;
- Pancreatic injury or pancreatitis within the last 6 months before randomization;
-
Non diabetic patients treated with SGLT-2 (SGLT:sodium glucose transport protein) inhibitors;
-
Combination use of ACEi and ARB within 3 months prior to randomization;
-
Concomitant therapy with nitrates, PDE5 inhibitors including nonspecific inhibitors (e.g. dipyridamole and theophylline), soluble guanylate cyclase [sGC] stimulators, renin inhibitors (within 4 weeks prior to randomization);
-
Participation in another clinical study or treatment with another investigational product 90 days prior to randomization;
-
Previous randomization in this study;
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hemoglobin A1c (HbA1c) >11%;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participant randomized to this arm will be sham-titrated. A 30-day safety follow up will be performed after end of treatment or after early discontinuation from the study. runcaciguat runcaciguat Participant randomized to this arm will be up-titrated. A 30-day safety follow up will be performed after end of treatment or after early discontinuation from the study.
- Primary Outcome Measures
Name Time Method Mean change in urinary albumin-to-creatinine ratio (UACR) from baseline to the average of multiple time points during treatment From baseline up to day 57 (± 3)
- Secondary Outcome Measures
Name Time Method Number of subjects with treatment emergent adverse event (TEAE) From first treatment administration up to end of follow up (Day 87±7) Number of subjects with early discontinuations From first treatment administration up to end of treatment (Day 57±3)
Trial Locations
- Locations (70)
Turun yliopistollinen keskussairaala
🇫🇮Turku, Finland
MCOMH Preventsia-2000
🇧🇬Stara Zagora, Bulgaria
Zentrum f. klinische Studien Dr. Hanusch GmbH
🇦🇹Wien, Austria
Edith Wolfson Medical Center
🇮🇱Holon, Israel
InnoDiab Forschung GmbH
🇩🇪Essen, Nordrhein-Westfalen, Germany
Universitätsklinikum AKH Wien
🇦🇹Wien, Austria
UZ Gent
🇧🇪Gent, Belgium
Klinik Landstraße - Krankenhaus Rudolfstiftung
🇦🇹Wien, Austria
Barzilai Medical Center | Nephrology & Hypertension Dept.
🇮🇱Ashkelon, Israel
Hôpital Erasme/Erasmus Ziekenhuis
🇧🇪Bruxelles - Brussel, Belgium
FMC-dialyzacne sluzby, s.r.o. - Kosice
🇸🇰Kosice, Slovakia
Hadassah Hebrew University Hospital Ein Kerem
🇮🇱Jerusalem, Israel
Ciutat Sanitaria i Universitaria de la Vall d'Hebron
🇪🇸Barcelona, Spain
Clalit Health Services Rabin Medical Center-Beilinson Campus
🇮🇱Petah Tikva, Israel
Klinik Hietzing
🇦🇹Wien, Austria
Complejo Hospitalario Universitario de Ferrol | Hospital Naval - Unidad de Hipertensión Arterial
🇪🇸Ferrol, A Coruña, Spain
PTC-Primary care Trial Center
🇸🇪Göteborg, Sweden
Hospital Universitario Virgen de las Nieves|Medicina Interna
🇪🇸Granada, Spain
DaVita Clinical Research Deutschland GmbH
🇩🇪Duesseldorf, Nordrhein-Westfalen, Germany
Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
A.O.U. Luigi Vanvitelli
🇮🇹Napoli, Campania, Italy
Poriya Medical Center | Nephrology and Hypertension Dept.
🇮🇱Tiberius, Israel
IRCCS Ospedale Policlinico San Martino
🇮🇹Genova, Liguria, Italy
Region Nordjylland | Aalborg University Hospital - Cardiology Department
🇩🇰Aalborg, Denmark
Regionshospitalet Gødstrup
🇩🇰Herning, Denmark
Holbæk Sygehus
🇩🇰Holbæk, Denmark
Sygehus Lillebaelt | Kolding Sygehus - Medicinske Sygdomme
🇩🇰Kolding, Denmark
Odense Universitetshospital, Endokrinologisk Afd. M
🇩🇰Odense C, Denmark
Medamed Studienambulanz GmbH
🇩🇪Leipzig, Sachsen, Germany
BIODIAL, spol. s r.o.
🇸🇰Puchov, Slovakia
OL Vrouwziekenhuis - Campus Aalst
🇧🇪Aalst, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Multiprofile Hospital for Active Treatment Medline Clinic
🇧🇬Plovdiv, Bulgaria
Med Centre Diamedical 2013
🇧🇬Dimitrovgrad, Bulgaria
MHAT Dr. Bratan Shukerov AD
🇧🇬Smolyan, Bulgaria
MHAT "Knyaginya Klementina - Sofia"EAD
🇧🇬Sofia, Bulgaria
MC Kalimat
🇧🇬Sofia, Bulgaria
Steno Diabetes Center Copenhagen
🇩🇰Herlev, Denmark
Omena Terveys Oy
🇫🇮Seinäjoki, Finland
Klinikum der Universität Würzburg
🇩🇪Wuerzburg, Bayern, Germany
Health Corporation of Galilee Medical Center
🇮🇱Nahariya, Israel
IRCCS Centro Cardiologico Monzino S.p.A
🇮🇹Milano, Lombardia, Italy
Istituto Ricerche Farmacologiche Mario Negri IRCCS
🇮🇹Bergamo, Lombardia, Italy
Ospedale San Raffaele s.r.l.
🇮🇹Milano, Lombardia, Italy
Complejo Hosp. Univ. A Coruña | Endocrinologia y Nutricion
🇪🇸A Coruña, Spain
Medivasa s.r.o.
🇸🇰Zilina, Slovakia
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Quirón
🇪🇸Barcelona, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Akademiska Sjukhuset Njurmottagningen
🇸🇪Uppsala, Sweden
ClinSmart
🇸🇪Uppsala, Sweden
Hospital Universitario Dr. Peset
🇪🇸Valencia, Spain
Dnepropetrovsk regional hospital n.a. I. I. Mechnikov
🇺🇦Dnipro, Ukraine
Clemenstorget Hjärtmottagning
🇸🇪Lund, Sweden
Medical center LLC " Fresenius medical care Ukraine"
🇺🇦Cherkasy, Ukraine
Private enterprise private production company " Acinus"
🇺🇦Kropyvnytskyi, Ukraine
Kyiv City Center of Nephrology and Dialysis
🇺🇦Kyiv, Ukraine
Medical Center of Edelweiss Medics LLC
🇺🇦Kyiv, Ukraine
Zaporizhzhia Regional Clinical Hospital
🇺🇦Zaporizhzhya, Ukraine
Herz- und Diabeteszentrum Nordrhein-Westfalen (HDZ NRW)
🇩🇪Bad Oeynhausen, Nordrhein-Westfalen, Germany
Satucon / Kuopion Työterveys
🇫🇮Kuopio, Finland
Volyn Regional Clinical Hospital
🇺🇦Lutsk, Ukraine
MHAT Sveta Karidad
🇧🇬Plovdiv, Bulgaria
StudyCor Oy
🇫🇮Jyväskylä, Finland
Ternopil Regional Clinical Hospital
🇺🇦Ternopil, Ukraine
Diagnos Klaukkalan Lääkäriasema
🇫🇮Klaukkala, Finland
Centralny Szpital Kliniczny MSWiA w Warszawie
🇵🇱Warszawa, Poland
A.O.U. di Bologna Policlinico S.Orsola Malpighi
🇮🇹Bologna, Emilia-Romagna, Italy
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Austria