Clinical trial NCT01874431: Safety and Efficacy of Different Oral Doses of BAY94-8862 in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Nephropathy
Official title: A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Safety and Efficacy of Different Oral Doses of BAY94-8862 in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Nephropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Nephropathies
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2013-06-11
Enrollment: 823
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To assess a new drug, BAY94-8862 given orally at different doses, to evaluate whether it was safe and can help the well being of patients with type 2 diabetes and diabetic nephropathy. These treatment doses were compared to placebo.


Eligibility criteria: Inclusion Criteria:

* Men and women aged 18 years and older.The lower age limit may be higher if legally required in the participating country
* Women of childbearing potential can only be included in the study if a pregnancy test is negative and if they agree to use adequate contraception when sexually active.
* Subjects with type 2 diabetes mellitus fulfilling at least 1 of the following criteria

  * are on oral antidiabetics and / or insulin,
  * have a documented fasting glucose \>/= 7.0 mmol/L in the medical history,
  * have a 2 hour plasma glucose \>/=11.1 mmol/L during an oral glucose tolerance test in the medical history, or
  * have a glycated hemoglobin (HbA1c) \>/=6.5% \[National Glycohemoglobin Standardization Program (NGSP) / Diabetes Control and Complications Trial (DCCT)\] in the medical history or at the run-in visit
* Subjects with a clinical diagnosis of diabetic nephropathy (DN) based on at least 1 of the following criteria:

  * Persistent very high albuminuria defined as urinary albumin-to-creatine ratio (UACR) of \>/=300 mg/g ( \>/= 34 mg/mmol) in 2 out of 3 first morning void samples and estimated glomerular filtration rate (eGFR) \>/=30 mL/min/1.73 m² but \< 90 mL/min/1.73m² (Chronic Kidney Disease Epidemiology Collaboration, CKD EPI) (mL = milliliter; min = minute; m2 = square meter; g = gram; mmol = millimole) or
  * Persistent high albuminuria defined as UACR of \>/=30 mg/g but \<300 mg/g in (\>/=3.4mg/mmol but \<34 mg/mmol) in 2 out of 3 first morning void samples and eGFR \>/=30 mL/min/1.73 m² but \< 90 mL/min/1.73m²
* Subjects treated with an angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) for at least 3 months without any adjustments to this therapy for at least 4 weeks prior to the screening visit
* Serum potassium \</= 4.8 mmol/L at both the run-in visit and the screening visit

Exclusion Criteria:

* Non-diabetic renal disease
* Glycated hemoglobin (HbA1c) \>12% at the run-in visit or the screening visit
* UACR \>3000 mg/g (339mg/mmol) in any of the urinary first morning void samples at the run-in visit or screening visit
* Hypertension with mean sitting systolic blood pressure (SBP) \>/=180 mmHg or mean sitting diastolic blood pressure (DBP) \>/=110 mmHg at the run-in visit or mean supine SBP \>/=160 mmHg or mean sitting DBP \>/=100 mmHg at the screening visit
* Subjects with a clinical diagnosis of heart failure with reduced ejection fraction (HFrEF) and persistent symptoms (New York Heart Association class II-IV) at the run-in visit
* Concomitant therapy with eplerenone, spironolactone, any renin inhibitor, or potassium-sparing diuretic
* Dialysis for acute renal failure within the previous 6 months prior to the run-in visit

Primary outcomes:
measure: Ratio of UACR at Day 90 to UACR at Baseline
timeFrame: Baseline and Day 90±2
Secondary outcomes:
measure: Change From Baseline to Day 90 in Serum Potassium
timeFrame: Baseline and Day 90±2
measure: Change From Baseline to Day 90 in eGFR
timeFrame: Baseline and Day 90±2
measure: Change From Baseline to Day 90 in KDQOL-36 Domain Score (Effects of Kidney Disease)
timeFrame: Baseline and Day 90±2
measure: Change From Baseline to Day 90 in EQ-5D Scores (EQ5D - Visual Analog Scale)
timeFrame: Baseline and Day 90±2
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Chula Vista
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Gatos
country: United States
state: California
city: New Haven
country: United States
state: Connecticut
city: Miami
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Flint
country: United States
state: Michigan
city: Flushing
country: United States
state: New York
city: Orangeburg
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Burlington
country: United States
state: Vermont
city: St Leonards
country: Australia
state: New South Wales
city: Clayton
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Prahran
country: Australia
state: Victoria
city: Reservoir
country: Australia
state: Victoria
city: Box Hill
country: Australia
city: Woolloongabba
country: Australia
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Salzburg
country: Austria
city: Salzburg
country: Austria
city: St. Pölten
country: Austria
city: Wien
country: Austria
city: Haskovo
country: Bulgaria
city: Lukovit
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Ruse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Stara Zagora
country: Bulgaria
city: Varna
country: Bulgaria
city: Varna
country: Bulgaria
city: Vancouver
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Courtice
country: Canada
state: Ontario
city: Kitchener
country: Canada
state: Ontario
city: Scarborough
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Chrudim
country: Czechia
city: Koprivnice
country: Czechia
city: Krnov
country: Czechia
city: Praha 2
country: Czechia
city: Aarhus C
country: Denmark
city: Gentofte
country: Denmark
city: Herlev
country: Denmark
city: Hillerød
country: Denmark
city: Holbaek
country: Denmark
city: Holstebro
country: Denmark
city: Kolding
country: Denmark
city: Helsinki
country: Finland
city: Jyväskylä
country: Finland
city: Oulu
country: Finland
city: Tampere
country: Finland
city: Turku
country: Finland
city: Amiens
country: France
city: La Tronche
country: France
city: Lyon Cedex
country: France
city: Paris Cedex 15
country: France
city: Strasbourg
country: France
city: Hannover
country: Germany
state: Niedersachsen
city: Bad Oeynhausen
country: Germany
state: Nordrhein-Westfalen
city: Düsseldorf
country: Germany
state: Nordrhein-Westfalen
city: Ludwigshafen
country: Germany
state: Rheinland-Pfalz
city: Neuwied
country: Germany
state: Rheinland-Pfalz
city: Hong Kong
country: Hong Kong
city: Shatin
country: Hong Kong
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Eger
country: Hungary
city: Nagykanizsa
country: Hungary
city: Papa
country: Hungary
city: Ashkelon
country: Israel
city: Holon
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Petach Tikva
country: Israel
city: Tel Aviv
country: Israel
city: Tel Aviv
country: Israel
city: Napoli
country: Italy
state: Campania
city: Bergamo
country: Italy
state: Lombardia
city: Bergamo
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Monza-Brianza
country: Italy
state: Lombardia
city: Foggia
country: Italy
state: Puglia
city: Cagliari
country: Italy
state: Sardegna
city: Pisa
country: Italy
state: Toscana
city: Padova
country: Italy
state: Veneto
city: Busan
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: AlMERE
country: Netherlands
city: Eindhoven
country: Netherlands
city: Groningen
country: Netherlands
city: Hoogeveen
country: Netherlands
city: Maastricht
country: Netherlands
city: Hamar
country: Norway
city: Ålesund
country: Norway
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Olawa
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Almada
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
city: Klipsruit West
country: South Africa
state: Gauteng
city: Krugersdorp
country: South Africa
state: Gauteng
city: Lenasia South
country: South Africa
state: Gauteng
city: Newtown
country: South Africa
state: Gauteng
city: Durban
country: South Africa
state: KwaZulu Natal
city: Durban
country: South Africa
state: KwaZulu Natal
city: Durban
country: South Africa
state: Kwazulu-Natal
city: Merebank
country: South Africa
state: Kwazulu-Natal
city: Tongaat
country: South Africa
state: Kwazulu-Natal
city: Cape Town
country: South Africa
state: Western Cape
city: Goodwood
country: South Africa
state: Western Cape
city: Somerset West
country: South Africa
state: Western Cape
city: Worcester
country: South Africa
state: Western Cape
city: Ferrol
country: Spain
state: A Coruña
city: Jerez de la Frontera
country: Spain
state: Cádiz
city: Sagunto
country: Spain
state: Valencia
city: Barcelona
country: Spain
city: Girona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Karlstad
country: Sweden
city: Kristianstad
country: Sweden
city: Skövde
country: Sweden
city: Stockholm
country: Sweden
city: Stockholm
country: Sweden
city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
city: Vällingby
country: Sweden
city: Örebro
country: Sweden
city: Kaohsiung
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, Remuzzi G, Rossing P, Schmieder RE, Nowack C, Kolkhof P, Joseph A, Pieper A, Kimmeskamp-Kirschbaum N, Ruilope LM; Mineralocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN) Study Group. Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial. JAMA. 2015 Sep 1;314(9):884-94. doi: 10.1001/jama.2015.10081.
citation: Snelder N, Heinig R, Drenth HJ, Joseph A, Kolkhof P, Lippert J, Garmann D, Ploeger B, Eissing T. Population Pharmacokinetic and Exposure-Response Analysis of Finerenone: Insights Based on Phase IIb Data and Simulations to Support Dose Selection for Pivotal Trials in Type 2 Diabetes with Chronic Kidney Disease. Clin Pharmacokinet. 2020 Mar;59(3):359-370. doi: 10.1007/s40262-019-00820-x.
citation: Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.
citation: Erraez S, Lopez-Mesa M, Gomez-Fernandez P. Mineralcorticoid receptor blockers in chronic kidney disease. Nefrologia (Engl Ed). 2021 May-Jun;41(3):258-275. doi: 10.1016/j.nefro.2020.10.001. Epub 2020 Dec 24. English, Spanish.