Anemia Studies in Chronic Kidney Disease: Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Non-Dialysis (ASCEND-ND)

Anaemia Clinical Trial

Official title:

A Phase 3 Randomized, Open-label (Sponsor-blind), Active-controlled, Parallel-group, Multi-center, Event Driven Study in Non-dialysis Subjects With Anemia Associated With Chronic Kidney Disease to Evaluate the Safety and Efficacy of Daprodustat Compared to Darbepoetin Alfa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02876835
• Other study ID #: 200808
• Secondary ID: 2016-000542-65
• Status: Completed
• Phase: Phase 3
• Start date: September 27, 2016
• Est. completion date: April 19, 2021

Study information

• Verified date: March 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this multi-center event-driven study in non-dialysis (ND) participants with anemia associated with chronic kidney disease (CKD) is to evaluate the safety and efficacy of daprodustat compared to darbepoetin alfa.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3872
• Est. completion date: April 19, 2021
• Est. primary completion date: April 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Age: 18 to 99 years of age (inclusive)

• CKD stage: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by electronic eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula.

• Erythropoietin-stimulating agents (ESAs)/Hgb: Group 1 (not using ESAs): No ESA use within the 6 weeks prior to screening and no ESA use between screening and randomization (Day 1). Group 2 (ESA users): Use of any approved ESA for the 6 weeks prior to screening and continuing between screening and randomization.

• For Group 1 (not using ESAs), Hgb concentration at Week -8 and Week 1 should be 8 to 10 gram per deciliter (g/dL). For Group 2 (ESA users), Hgb concentration at Week -8 should be 8 to 12 g/dL and at Week 1 should be 8 to 11 g/dL.

• >=80% and <=120% compliance with placebo during run-in period.

• Informed consent (screening only): capable of giving signed informed consent which includes compliance with the requirements and restrictions.

Exclusion Criteria:

• Dialysis: On dialysis or clinical evidence of impending need to initiate dialysis within 90 days after study start (Day 1).

• Kidney transplant: Planned living-related or living-unrelated kidney transplant within 52 weeks after study start (Day 1).

• Ferritin: <=100 nanograms (ng)/milliliter (mL) (<=100 micrograms/liter [L]) at screening.

• Transferrin saturation (TSAT) (screening only): <=20%.

• Aplasias: History of bone marrow aplasia or pure red cell aplasia.

• Other causes of anemia: untreated pernicious anemia, thalassemia major, sickle cell disease or myelodysplastic syndrome.

• Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant GI bleeding <=4 weeks prior to screening through to randomization (Day 1).

• MI or acute coronary syndrome: <=4 weeks prior to screening through to randomization (Day 1).

• Stroke or transient ischemic attack: <=4 weeks prior to screening through to randomization (Day 1).

• Heart failure (HF): Chronic Class IV HF, as defined by the New York Heart Association (NYHA) functional classification system.

• Current uncontrolled hypertension: Current uncontrolled hypertension as determined by the investigator.

• Bazett's corrected QT interval (QTcB) (Day 1): QTcB >500 millisecond (msec), or QTcB >530 msec in subjects with bundle branch block. There is no Q-T Interval Corrected for Heart Rate (QTc) exclusion for subjects with a predominantly ventricular paced rhythm.

• Alanine transaminase (ALT): >2x upper limit of normal (ULN) at screening.

• Bilirubin: >1.5xULN at screening.

• Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.

• Malignancy: History of malignancy within the 2 years prior to screening through to randomization (Day 1) or currently receiving treatment for cancer, or complex kidney cyst (example [e.g.] Bosniak Category II F, III or IV) > 3 centimeter (cm); with the exception of localized squamous cell or basal cell carcinoma of the skin that has been definitively treated >=4 weeks prior to screening.

• Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product, or darbepoetin alfa.

• Drugs and supplements: Use of strong inhibitors of Cytochrome P4502C8 (CYP2C8) (e.g., gemfibrozil) or strong inducers of CYP2C8 (e.g., rifampin/rifampicin).

• Other study participation: Use of other investigational agent or device prior to screening through to randomization (Day 1). At screening, this exclusion applies to use of the investigational agent within 30 days or within five half lives (whichever is longer).

• Prior treatment with daprodustat: Any prior treatment with daprodustat for treatment duration of >30 days.

• Females only: Subject is pregnant [as confirmed by a positive urine human chorionic gonadotrophin (hCG) test for females of reproductive potential (FRP) only], subject is breastfeeding, or subject is of reproductive potential and does not agree to follow one of the contraceptive options.

• Other Conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance (e.g., intolerance to darbepoetin alfa) or prevent understanding of the aims or investigational procedures or possible consequences of the study.

Related Conditions & MeSH terms

• Anaemia
• Anemia
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Daprodustat
The initial dose or oral daprodustat for ESA naïve subjects is based on Hgb and for ESA users is based on prior ESA dose. The dose is adjusted thereafter in order to achieve the target range.
• Darbepoetin alfa
The initial dose of darbepoetin alfa to be administered for SC injection for ESA naïve subjects is based in Hgb and weight, and for ESA users is based on converting the prior ESA dose to the nearest available study darbepoetin alfa dose. The dose is adjusted thereafter in order to achieve the target range. IV darbepoetin alfa can be considered for participants transitioning to hemodialysis.
• Placebo
Oral placebo tablets will be taken from Week -4 up to randomization (Day 1).
• Iron Therapy
Participants will receive supplemental iron therapy if ferritin is <=100 ng/mL or TSAT is <=20%. The investigator will choose the route of administration and dose of iron.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Evita	Buenos Aires
Argentina	GSK Investigational Site	Cordoba	Córdova
Argentina	GSK Investigational Site	Córdoba	Córdova
Argentina	GSK Investigational Site	Córdoba	Córdova
Argentina	GSK Investigational Site	Coronel Suarez	Buenos Aires
Argentina	GSK Investigational Site	Corrientes
Argentina	GSK Investigational Site	Formosa
Argentina	GSK Investigational Site	Junín	Buenos Aires
Argentina	GSK Investigational Site	La Plata
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Moron
Argentina	GSK Investigational Site	Pergamino	Buenos Aires
Argentina	GSK Investigational Site	San Miguel de Tucumán
Australia	GSK Investigational Site	Concord	New South Wales
Australia	GSK Investigational Site	Garran	Australian Capital Territory
Australia	GSK Investigational Site	Gosford	New South Wales
Australia	GSK Investigational Site	Kingswood	New South Wales
Australia	GSK Investigational Site	Kogarah	New South Wales
Australia	GSK Investigational Site	Liverpool
Australia	GSK Investigational Site	Melbourne	Victoria
Australia	GSK Investigational Site	Nambour	Queensland
Australia	GSK Investigational Site	Nedlands	Western Australia
Australia	GSK Investigational Site	Randwick	New South Wales
Australia	GSK Investigational Site	Reservoir	Victoria
Australia	GSK Investigational Site	St Albans	Victoria
Australia	GSK Investigational Site	St Leonards	New South Wales
Australia	GSK Investigational Site	Wollongong	New South Wales
Belgium	GSK Investigational Site	Aalst
Belgium	GSK Investigational Site	Baudour
Belgium	GSK Investigational Site	Brugge
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Ieper
Belgium	GSK Investigational Site	Leuven
Belgium	GSK Investigational Site	Liège
Belgium	GSK Investigational Site	Roeselare
Belgium	GSK Investigational Site	Ronse
Belgium	GSK Investigational Site	Sint-Niklaas
Brazil	GSK Investigational Site	Belo Horizonte
Brazil	GSK Investigational Site	Brasilia
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Feira de Santana
Brazil	GSK Investigational Site	Joinville
Brazil	GSK Investigational Site	Juiz De Fora
Brazil	GSK Investigational Site	Passo Fundo	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Salvador	Bahia
Brazil	GSK Investigational Site	Sao Jose do Rio Preto	São Paulo
Brazil	GSK Investigational Site	Sao Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	Votuporanga	São Paulo
Bulgaria	GSK Investigational Site	Blagoevgrad
Bulgaria	GSK Investigational Site	Burgas
Bulgaria	GSK Investigational Site	Dobrich
Bulgaria	GSK Investigational Site	Gabrovo
Bulgaria	GSK Investigational Site	Lom
Bulgaria	GSK Investigational Site	Pazardzhik
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Sliven
Bulgaria	GSK Investigational Site	Smolyan
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Stara Zagora
Bulgaria	GSK Investigational Site	Varna
Bulgaria	GSK Investigational Site	Veliko Tarnovo
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Greenfield Park	Quebec
Canada	GSK Investigational Site	Halifax	Nova Scotia
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Mississauga	Ontario
Canada	GSK Investigational Site	Mississauga	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Colombia	GSK Investigational Site	Barranquilla
Colombia	GSK Investigational Site	Bogotá
Colombia	GSK Investigational Site	Cali
Colombia	GSK Investigational Site	Floridablanca
Colombia	GSK Investigational Site	Medellin
Czechia	GSK Investigational Site	Beroun
Czechia	GSK Investigational Site	Cesky Krumlov
Czechia	GSK Investigational Site	Ivancice
Czechia	GSK Investigational Site	Jilemnice
Czechia	GSK Investigational Site	Marianske Lazne
Czechia	GSK Investigational Site	Novy Jicin
Czechia	GSK Investigational Site	Pardubice
Czechia	GSK Investigational Site	Praha 2
Czechia	GSK Investigational Site	Praha 4
Czechia	GSK Investigational Site	Sokolov
Denmark	GSK Investigational Site	Aalborg
Denmark	GSK Investigational Site	Holstebro
Denmark	GSK Investigational Site	Kolding
Denmark	GSK Investigational Site	Odense C
Estonia	GSK Investigational Site	Jämejala Village
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tartu
France	GSK Investigational Site	Annonay
France	GSK Investigational Site	Boulogne Billancourt
France	GSK Investigational Site	Caen Cedex 9
France	GSK Investigational Site	Clermont-Ferrand
France	GSK Investigational Site	Lyon
France	GSK Investigational Site	Montpellier
France	GSK Investigational Site	Mulhouse
France	GSK Investigational Site	Poitiers
France	GSK Investigational Site	Saint-Ouen
Germany	GSK Investigational Site	Cloppenburg	Niedersachsen
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Kaiserslautern	Rheinland-Pfalz
Germany	GSK Investigational Site	Koeln
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenster	Nordrhein-Westfalen
Germany	GSK Investigational Site	Wiesbaden
Greece	GSK Investigational Site	Alexandroupolis
Greece	GSK Investigational Site	Arta
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Efkarpia
Greece	GSK Investigational Site	Heraklion-Crete
Greece	GSK Investigational Site	Ioannina
Greece	GSK Investigational Site	Ioannina
Greece	GSK Investigational Site	Komotini
Greece	GSK Investigational Site	Larissa
Greece	GSK Investigational Site	Melissia
Greece	GSK Investigational Site	Patras
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Hong Kong	GSK Investigational Site	Hong Kong
Hong Kong	GSK Investigational Site	Lai Chi kok
Hong Kong	GSK Investigational Site	New Territories
Hong Kong	GSK Investigational Site	Tsuen Wan
Hungary	GSK Investigational Site	Baja
Hungary	GSK Investigational Site	Balatonfured
Hungary	GSK Investigational Site	Esztergom
Hungary	GSK Investigational Site	Kecskemét
Hungary	GSK Investigational Site	Miskolc
Hungary	GSK Investigational Site	Pecs
Hungary	GSK Investigational Site	Salgótarján
Hungary	GSK Investigational Site	Szigetvar
India	GSK Investigational Site	Ahmedabad
India	GSK Investigational Site	Ahmedabad
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Calicut
India	GSK Investigational Site	Chandigarh
India	GSK Investigational Site	Chennai
India	GSK Investigational Site	Chennai, Tamil Nadu
India	GSK Investigational Site	Delhi
India	GSK Investigational Site	Ghaziabad
India	GSK Investigational Site	Gurgaon
India	GSK Investigational Site	Hyderabad
India	GSK Investigational Site	Hyderabad
India	GSK Investigational Site	Jaipur
India	GSK Investigational Site	Jaipur
India	GSK Investigational Site	Lucknow
India	GSK Investigational Site	Manipal
India	GSK Investigational Site	Mumbai
India	GSK Investigational Site	Mumbai
India	GSK Investigational Site	Nadiad
India	GSK Investigational Site	Nagpur
India	GSK Investigational Site	New Delhi
India	GSK Investigational Site	New Delhi
India	GSK Investigational Site	New Delhi
India	GSK Investigational Site	New Delhi
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Secunderabad
India	GSK Investigational Site	Trivandrum
Israel	GSK Investigational Site	Ashkelon
Israel	GSK Investigational Site	Hadera
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Kfar Saba
Israel	GSK Investigational Site	Nahariya
Israel	GSK Investigational Site	Nazareth
Israel	GSK Investigational Site	Poriya
Israel	GSK Investigational Site	Zerifin
Italy	GSK Investigational Site	Cagliari	Sardegna
Italy	GSK Investigational Site	Catanzaro	Calabria
Italy	GSK Investigational Site	Foggia	Puglia
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Imola
Italy	GSK Investigational Site	Lecco	Lombardia
Italy	GSK Investigational Site	Mestre
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Napoli	Campania
Italy	GSK Investigational Site	Pavia	Lombardia
Italy	GSK Investigational Site	Piacenza	Emilia-Romagna
Italy	GSK Investigational Site	Reggio Emilia	Emilia-Romagna
Italy	GSK Investigational Site	Torino	Piemonte
Korea, Republic of	GSK Investigational Site	Anyang-Si, Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Bucheon
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Daejeon
Korea, Republic of	GSK Investigational Site	Goyang-si
Korea, Republic of	GSK Investigational Site	Ilsanseo-gu, Goyang-si,
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Jeonju-si
Korea, Republic of	GSK Investigational Site	Seongnam
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Suwon
Korea, Republic of	GSK Investigational Site	Suwon
Korea, Republic of	GSK Investigational Site	Uijeongbu-si
Korea, Republic of	GSK Investigational Site	Wonju-si
Malaysia	GSK Investigational Site	Alor Setar
Malaysia	GSK Investigational Site	Ipoh
Malaysia	GSK Investigational Site	Kuala Lumpur
Malaysia	GSK Investigational Site	Kuantan
Malaysia	GSK Investigational Site	Lumut
Malaysia	GSK Investigational Site	Pahang
Malaysia	GSK Investigational Site	Penang
Mexico	GSK Investigational Site	Aguascalientes
Mexico	GSK Investigational Site	Chihuahua
Mexico	GSK Investigational Site	Chihuahua
Mexico	GSK Investigational Site	Ciudad De Mexico	Estado De México
Mexico	GSK Investigational Site	Ciudad De México
Mexico	GSK Investigational Site	Ciudad De México
Mexico	GSK Investigational Site	Cuernavaca	Morelos
Mexico	GSK Investigational Site	Culiacan	Sinaloa
Mexico	GSK Investigational Site	Culiacan	Sinaloa
Mexico	GSK Investigational Site	Culiacan
Mexico	GSK Investigational Site	Durango.	Durango
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Guadalajara.	Jalisco
Mexico	GSK Investigational Site	Leon	Guanajuato
Mexico	GSK Investigational Site	León	Guanajuato
Mexico	GSK Investigational Site	Mazatlán	Sinaloa
Mexico	GSK Investigational Site	Merida	Yucatán
Mexico	GSK Investigational Site	Merida	Yucatán
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Queretaro	Querétaro
Mexico	GSK Investigational Site	Saltillo	Coahuila
Mexico	GSK Investigational Site	Tlalnepantla De Baz
Mexico	GSK Investigational Site	Torreon	Coahuila
Mexico	GSK Investigational Site	Veracruz
Mexico	GSK Investigational Site	Zapopan, Jalisco
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Deventer
Netherlands	GSK Investigational Site	Rotterdam
New Zealand	GSK Investigational Site	Dunedin
New Zealand	GSK Investigational Site	Hamilton
New Zealand	GSK Investigational Site	Hastings
New Zealand	GSK Investigational Site	Otahuhu
New Zealand	GSK Investigational Site	Takapuna, Auckland
Philippines	GSK Investigational Site	Baguio City, Benguet
Philippines	GSK Investigational Site	Cebu City
Philippines	GSK Investigational Site	Dasmarinas
Philippines	GSK Investigational Site	Iloilo City
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Pasig
Philippines	GSK Investigational Site	Quezon City
Philippines	GSK Investigational Site	San Juan
Philippines	GSK Investigational Site	Sto Tomas
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Brzeg
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Kielce
Poland	GSK Investigational Site	Kolobrzeg
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Radom
Poland	GSK Investigational Site	Szczecin
Poland	GSK Investigational Site	Zyrardow
Portugal	GSK Investigational Site	Amadora
Portugal	GSK Investigational Site	Aveiro
Portugal	GSK Investigational Site	Covilhã
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Torres Novas
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Constanta
Romania	GSK Investigational Site	Oradea
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Irkutsk
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Krasnodar
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Mytischi
Russian Federation	GSK Investigational Site	Omsk
Russian Federation	GSK Investigational Site	Podolsk
Russian Federation	GSK Investigational Site	Ryazan
Russian Federation	GSK Investigational Site	Smolensk
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	Ulyanovsk
Russian Federation	GSK Investigational Site	Volzhsky
Russian Federation	GSK Investigational Site	Yaroslavl
Singapore	GSK Investigational Site	Singapore
Singapore	GSK Investigational Site	Singapore
Singapore	GSK Investigational Site	Singapore
Singapore	GSK Investigational Site	Singapore
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Cape Town.
South Africa	GSK Investigational Site	Port Elizabeth	Eastern Cape
South Africa	GSK Investigational Site	Somerset West
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Burela
Spain	GSK Investigational Site	Caceres
Spain	GSK Investigational Site	Ciudad Real
Spain	GSK Investigational Site	Girona
Spain	GSK Investigational Site	Guadalajara
Spain	GSK Investigational Site	L'Hospitalet de Llobregat
Spain	GSK Investigational Site	Majadahonda	Madrid
Spain	GSK Investigational Site	Mollet del Valles
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Sevilla
Sweden	GSK Investigational Site	Örebro
Sweden	GSK Investigational Site	Stockholm
Sweden	GSK Investigational Site	Uppsala
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	Keelung
Taiwan	GSK Investigational Site	New Taipei
Taiwan	GSK Investigational Site	Tainan
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taoyuan Hsien
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkoknoi
Thailand	GSK Investigational Site	Chiang Mai
Thailand	GSK Investigational Site	Khon Kaen
Thailand	GSK Investigational Site	Pathumthani
Turkey	GSK Investigational Site	Adana
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Antalya
Turkey	GSK Investigational Site	Edirne
Turkey	GSK Investigational Site	Eskisehir
Turkey	GSK Investigational Site	Istanbul
Turkey	GSK Investigational Site	Istanbul
Turkey	GSK Investigational Site	Istanbul
Turkey	GSK Investigational Site	Kayseri
Ukraine	GSK Investigational Site	Cherkasy
Ukraine	GSK Investigational Site	Chernihiv
Ukraine	GSK Investigational Site	Chernivtsi
Ukraine	GSK Investigational Site	Ivano-Frankivsk
Ukraine	GSK Investigational Site	Kharkiv
Ukraine	GSK Investigational Site	Kherson
Ukraine	GSK Investigational Site	Kiev
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Lutsk
Ukraine	GSK Investigational Site	Mykolaiv
Ukraine	GSK Investigational Site	Poltava
Ukraine	GSK Investigational Site	Ternopil
Ukraine	GSK Investigational Site	Zaporizhzhia
Ukraine	GSK Investigational Site	Zaporizhzhia
Ukraine	GSK Investigational Site	Zhytomyr
United Kingdom	GSK Investigational Site	Birmingham
United Kingdom	GSK Investigational Site	Bristol
United Kingdom	GSK Investigational Site	Cambridge
United Kingdom	GSK Investigational Site	Cardiff
United Kingdom	GSK Investigational Site	Derby
United Kingdom	GSK Investigational Site	Doncaster
United Kingdom	GSK Investigational Site	Fife
United Kingdom	GSK Investigational Site	Glasgow.
United Kingdom	GSK Investigational Site	Hampstead	London
United Kingdom	GSK Investigational Site	Hull
United Kingdom	GSK Investigational Site	Leeds
United Kingdom	GSK Investigational Site	Liverpool	Merseyside
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Middlesbrough
United Kingdom	GSK Investigational Site	Oxford
United Kingdom	GSK Investigational Site	Preston	Lancashire
United Kingdom	GSK Investigational Site	Salford
United Kingdom	GSK Investigational Site	Stevenage	Hertfordshire
United Kingdom	GSK Investigational Site	Wolverhampton	West Midlands
United Kingdom	GSK Investigational Site	York
United States	GSK Investigational Site	Alexandria	Virginia
United States	GSK Investigational Site	Andalusia	Alabama
United States	GSK Investigational Site	Anderson	South Carolina
United States	GSK Investigational Site	Arlington	Texas
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Augusta	Georgia
United States	GSK Investigational Site	Augusta	Georgia
United States	GSK Investigational Site	Augusta	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Aventura	Florida
United States	GSK Investigational Site	Azusa	California
United States	GSK Investigational Site	Bakersfield	California
United States	GSK Investigational Site	Bakersfield	California
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Baton Rouge	Louisiana
United States	GSK Investigational Site	Baton Rouge	Louisiana
United States	GSK Investigational Site	Bethlehem	Pennsylvania
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Bluefield	West Virginia
United States	GSK Investigational Site	Boca Raton	Florida
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Brooklyn	New York
United States	GSK Investigational Site	Buffalo	New York
United States	GSK Investigational Site	Canton	Ohio
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Chula Vista	California
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Columbia	South Carolina
United States	GSK Investigational Site	Columbus	Georgia
United States	GSK Investigational Site	Coral Gables	Florida
United States	GSK Investigational Site	Cordova	Tennessee
United States	GSK Investigational Site	Corpus Christi	Texas
United States	GSK Investigational Site	Corsicana	Texas
United States	GSK Investigational Site	Crystal Lake	Illinois
United States	GSK Investigational Site	Cudahy	California
United States	GSK Investigational Site	Cutler Bay	Florida
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Des Moines	Iowa
United States	GSK Investigational Site	Detroit	Michigan
United States	GSK Investigational Site	Doral	Florida
United States	GSK Investigational Site	Doylestown	Pennsylvania
United States	GSK Investigational Site	El Centro	California
United States	GSK Investigational Site	Escondido	California
United States	GSK Investigational Site	Fairfax	Virginia
United States	GSK Investigational Site	Flushing	New York
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Fort Wayne	Indiana
United States	GSK Investigational Site	Glendale	Arizona
United States	GSK Investigational Site	Glendale	California
United States	GSK Investigational Site	Granada Hills	California
United States	GSK Investigational Site	Grand Forks	North Dakota
United States	GSK Investigational Site	Hampton	Virginia
United States	GSK Investigational Site	Homestead	Florida
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Hudson	Florida
United States	GSK Investigational Site	Huntsville	Alabama
United States	GSK Investigational Site	Hutchinson	Kansas
United States	GSK Investigational Site	Iowa City	Iowa
United States	GSK Investigational Site	Jackson	Mississippi
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Jeffersonville	Indiana
United States	GSK Investigational Site	Kalamazoo	Michigan
United States	GSK Investigational Site	Knoxville	Tennessee
United States	GSK Investigational Site	La Mesa	California
United States	GSK Investigational Site	La Palma	California
United States	GSK Investigational Site	Lancaster	Pennsylvania
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Lauderdale Lakes	Florida
United States	GSK Investigational Site	Laurelton	New York
United States	GSK Investigational Site	Lawton	Oklahoma
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Lufkin	Texas
United States	GSK Investigational Site	McAllen	Texas
United States	GSK Investigational Site	Memphis	Tennessee
United States	GSK Investigational Site	Mentor	Ohio
United States	GSK Investigational Site	Mesa	Arizona
United States	GSK Investigational Site	Metairie	Louisiana
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami Gardens	Florida
United States	GSK Investigational Site	Miami Lakes	Florida
United States	GSK Investigational Site	Michigan City	Indiana
United States	GSK Investigational Site	Middlebury	Connecticut
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Montebello	California
United States	GSK Investigational Site	Mount Prospect	Illinois
United States	GSK Investigational Site	Nampa	Idaho
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	National City	California
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	North Platte	Nebraska
United States	GSK Investigational Site	Ocala	Florida
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Pembroke Pines	Florida
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Pontiac	Michigan
United States	GSK Investigational Site	Port Charlotte	Florida
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Potomac	Maryland
United States	GSK Investigational Site	Quincy	Illinois
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Ridgewood	New York
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	Rocky Mount	North Carolina
United States	GSK Investigational Site	Roseburg	Oregon
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	Salem	Virginia
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Luis Obispo	California
United States	GSK Investigational Site	Scottsdale	Arizona
United States	GSK Investigational Site	Simi Valley	California
United States	GSK Investigational Site	South Miami	Florida
United States	GSK Investigational Site	Springfield	Illinois
United States	GSK Investigational Site	Sumter	South Carolina
United States	GSK Investigational Site	Takoma Park	Maryland
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Tarzana	California
United States	GSK Investigational Site	Temple	Texas
United States	GSK Investigational Site	Temple Terrace	Florida
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Tupelo	Mississippi
United States	GSK Investigational Site	Upland	Pennsylvania
United States	GSK Investigational Site	Washington	District of Columbia
United States	GSK Investigational Site	Waxahachie	Texas
United States	GSK Investigational Site	Whittier	California
United States	GSK Investigational Site	Wichita	Kansas
United States	GSK Investigational Site	Wilmington	North Carolina
United States	GSK Investigational Site	Winston-Salem	North Carolina
United States	GSK Investigational Site	Wyomissing	Pennsylvania
United States	GSK Investigational Site	Yonkers	New York
Vietnam	GSK Investigational Site	Ha Noi
Vietnam	GSK Investigational Site	Ha Noi City
Vietnam	GSK Investigational Site	Hai Phong
Vietnam	GSK Investigational Site	Hanoi
Vietnam	GSK Investigational Site	Ho Chi Minh
Vietnam	GSK Investigational Site	Ho Chi Minh City

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  Colombia,  Czechia,  Denmark,  Estonia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (2)

Ajay K. Singh, Kevin Carroll, John J. V. McMurray, Scott Solomon, Vivekanand Jha, Kirsten L. Johansen, Renato D. Lopes, Iain C. Macdougall, Gregorio T. Obrador, Sushrut S. Waikar, Christoph Wanner, David C. Wheeler, Andrzej Wiecek, Allison Blackorby, Borut Cizman, Alexander R. Cobitz, Rich Davies, Tara L. DiMino, Lata Kler, Amy M. Meadowcroft, Lin Taft, Vlado Perkovic for the ASCEND-ND Study Group. DAPRODUSTAT FOR THE TREATMENT OF ANEMIA IN PATIENTS NOT UNDERGOING DIALYSIS. N Engl J Med. 2021; DOI: 10.1056/NEJMoa2113380 PMID: 34739196

Perkovic V, Blackorby A, Cizman B, Carroll K, Cobitz AR, Davies R, DiMino TL, Jha V, Johansen KL, Lopes RD, Kler L, Macdougall IC, McMurray JJV, Meadowcroft AM, Obrador GT, Solomon S, Taft L, Wanner C, Waikar SS, Wheeler DC, Wiecek A, Singh AK. The ASCEND-ND trial: study design and participant characteristics. Nephrol Dial Transplant. 2022 Oct 19;37(11):2157-2170. doi: 10.1093/ndt/gfab318. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period (Non-inferiority Analysis)	Time to MACE defined as time to first occurrence of Clinical Events Committee (CEC) adjudicated MACE (composite of all-cause mortality, non-fatal myocardial infarction [MI] and non-fatal stroke) was analyzed using a Cox proportional hazards regression model with treatment group, current erythropoiesis-stimulating agents (ESA) use at randomization and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) plus (+) 1. The incidence rate per 100 person years calculated as (100 multiplied [*] number of participants with at least 1 event) divided by [/] first event person-years) is presented along with 95 percent (%) confidence interval (CI). First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Primary	Mean Change From Baseline in Hgb Levels Over the Evaluation Period (Week 28 to Week 52)	Blood samples were collected from participants for Hgb measurements. Hgb during the evaluation period was defined as the mean of all available post-randomization Hgb values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis missing post-Baseline Hgb values were imputed using pre-specified multiple imputation methods. Change from Baseline was defined as post-Baseline value minus (-) Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using the Analysis of covariance (ANCOVA) model with terms for treatment, Baseline Hgb, current ESA use and region.	Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)
Secondary	Time to First Occurrence of Adjudicated MACE During CV Events Follow-up Time Period (Superiority Analysis)	Time to MACE defined as the time to first occurrence of CEC adjudicated MACE was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariate. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Adjudicated MACE or Thromboembolic Event During CV Events Follow-up Time Period	Time to first occurrence of adjudicated MACE or thromboembolic event (vascular access thrombosis, symptomatic deep vein thrombosis or symptomatic pulmonary embolism) was analyzed using a Cox proportional hazards regression model with with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure During CV Events Follow-up Time Period	Time to first occurrence of adjudicated MACE or hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Chronic Kidney Disease (CKD) Progression During CV Events Follow-up Time Period	Progression of CKD defined as: 40% decline in estimated glomerular filtration rate (eGFR) from Baseline or end stage renal disease (ESRD) as defined by either initiating chronic dialysis for >=90 days or not initiating chronic dialysis when dialysis is indicated or kidney transplantation. Time to first occurrence of CKD progression was analyzed using Fine and Gray's proportional subdistribution hazard regression model with treatment group, Baseline ESA use and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) +1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Adjudicated All-Cause Mortality During Vital Status for Follow-up Time Period	Time to first occurrence of adjudicated all-cause mortality was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the vital status follow-up time period.	Up to 4.3 person-years for vital status follow-up time period
Secondary	Time to First Occurrence of Adjudicated CV Mortality During CV Events Follow-up Time Period	Time to first occurrence of adjudicated CV mortality was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) During CV Events Follow-up Time Period	Time to first occurrence of adjudicated MI (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Adjudicated Stroke (Fatal and Non-Fatal) During CV Events Follow-up Time Period	Time to first occurrence of adjudicated stroke (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis)	Number of participants with adjudicated MACE or hospitalization for heart failure (recurrent events analysis) is presented, categorized by number of occurrences of adjudicated MACE or hospitalization for heart failure per participant.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI During CV Events Follow-up Time Period	Time to first occurrence of adjudicated CV mortality or non-fatal MI was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of All-Cause Hospitalization During CV Events Follow-up Time Period	All-cause hospitalization events were hospital admissions recorded on the hospitalization electronic case report form (eCRF) form with a hospitalization duration >=24 hours. Time to first occurrence of all-cause hospitalization was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of All-Cause Hospital Re-admission Within 30 Days During CV Events Follow-up Time Period	All-cause hospital re-admissions within 30days are defined as hospital admissions recorded on hospitalization electronic case record form with hospitalization duration of >=24 hours and admission date within 30days following previous discharge date of all-cause hospitalization event, where previous hospitalization was >=24hours.Time to first occurrence of all-cause hospital re-admission within 30days was analyzed using Cox proportional hazards regression model with treatment group, current ESA use at randomization and region as covariates.Time to the first occurrence was computed as(event date - randomization date)+1. Incidence rate per 100 person years calculated as(100*number of participants with at least 1event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic Events During CV Events Follow-up Time Period	Time to first occurrence of adjudicated MACE or hospitalization for heart failure or thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Adjudicated Hospitalization for Heart Failure During CV Events Follow-up Time Period	Time to first occurrence of adjudicated hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Adjudicated Thromboembolic Events During CV Events Follow-up Time Period	Time to first occurrence of adjudicated thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Confirmed 40% Decline in eGFR During CV Events Follow-up Time Period	Time to first occurrence of confirmed 40% decline in eGFR was analyzed using a Fine & Gray's proportional subdistribution hazard regression model with treatment group, Baseline ESA use and region as covariates. Time to the first occurrence was computed as (event date minus randomization date)+1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Chronic Dialysis During CV Events Follow-up Time Period	Time to first occurrence of chronic dialysis was analyzed using a Fine & Gray's proportional subdistribution hazard regression model with treatment group, Baseline ESA use and region as covariates. Chronic dialysis is defined by either initiating dialysis for >=90 days or not initiating chronic dialysis when dialysis is indicated. Time to the first occurrence was computed as (event date minus randomization date)+1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Time to First Occurrence of Kidney Transplant During CV Events Follow-up Time Period	Time to first occurrence of kidney transplant were analyzed using a Fine & Gray's proportional subdistribution hazard regression model with treatment group, Baseline ESA use and region as covariates. Time to the first occurrence was computed as (event date minus randomization date)+1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.	Up to 4.3 person-years for CV follow-up time period
Secondary	Change From Baseline in Post-randomization Hgb Levels at Week 52	Blood samples were collected from participants for Hgb measurements. Change from Baseline was defined as post-randomization value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using mixed model repeated measures (MMRM) model fitted from Baseline up to Week 52, excluding values collected during the stabilization period, with factors for treatment, time, current ESA use, region, Baseline Hgb and Baseline Hgb by time and treatment by time interactions.	Baseline (Pre-dose on Day 1) and Week 52
Secondary	Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)	Mean Hgb during the evaluation period was defined as the mean of all evaluable Hgb values during the evaluation period (Week 28 to Week 52) including any evaluable unscheduled Hgb values that were taken during this time period. Hgb responders were defined as participants with a mean Hgb during the evaluation period that falls within the Hgb analysis range of 10-11.5 g/dL.	Week 28 to Week 52
Secondary	Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis	Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / [Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) - Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)].	Week 28 to Week 52
Secondary	Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority Analysis	Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / [Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) - Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)].	Week 28 to Week 52
Secondary	Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Non-inferiority Analysis	Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / [Earlier of (Date of the last evaluable Hgb value, End of study date)- Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)].	Week 28 to end of study (4.3 person-years for follow-up time period)
Secondary	Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Superiority Analysis	Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / [Earlier of (Date of the last evaluable Hgb value, End of study date)- Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)].	Week 28 to end of study (4.3 person-years for follow-up time period)
Secondary	Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52	SBP, DBP and MAP were measured in a seated position after at least a 5-minutes of rest. MAP is the average (BP) in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using MMRM model with treatment group + time + current ESA use at randomization + region + Baseline value + Baseline value*time + treatment group*time, using an unstructured covariance matrix. Data for post-dialysis BP measurements have been presented.	Baseline (Week -4) and Week 52
Secondary	Change From Baseline in SBP, DBP, MAP at End of Treatment	SBP, DBP and MAP were measured in a seated position after at least a 5-minutes of rest. MAP is an average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using ANCOVA model with terms for treatment group, current ESA use at randomization, region and Baseline value. Data for post-dialysis BP measurements have been presented.	Baseline (Week -4) and 51.1 months
Secondary	Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years	BP exacerbation event (based on post-dialysis) was defined as: SBP >= 25 millimeter of mercury (mmHg) increased from Baseline or SBP >=180 mmHg; DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. The BP exacerbation events per 100 participant years was estimated using the negative binomial model with treatment, current ESA use at randomization and region as covariates and the logarithm of time on-treatment as an offset variable. Data for post-dialysis BP measurements have been presented.	Day 1 to end of treatment (51.1 months)
Secondary	Number of Participants With at Least One BP Exacerbation Event During Study	BP exacerbation was defined as: SBP >= 25 mmHg increased from Baseline or SBP >=180 mmHg; DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. Number of participants with at least one BP exacerbation event is presented.	Day 1 to end of treatment (51.1 months)
Secondary	Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria	Percentage of participants permanently stopping randomized treatment due to meeting rescue criteria has been presented.	Day 1 to 51.1 months
Secondary	Change From Baseline in On-treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52	The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). The PCS is an average score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. PCS ranges from 0 to 100; higher score represents better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.	Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary	Change From Baseline in On-treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52	The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). MCS is an average score derived from 4 domains (vitality, social functioning, role-emotional and mental health) representing overall mental health. MCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.	Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary	Change From Baseline in On-treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52	The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: bodily pain (b pain), general health (GH), mental health (MH), role-emotional (RE) (role limitations caused by emotional problems), role-physical (RP) (role limitations caused by physical problems), social functioning (SF), physical functioning and vitality. Each domain is scored from 0 (poorer health) to 100 (better health). Each domain score ranges from 0 to 100, higher score indicates a better health state and better functioning. Change from Baseline (BL) was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.	Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary	Change From Baseline in On-treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52	The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Vitality score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.	Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary	Change From Baseline in On-treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52	The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Physical functioning score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.	Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary	Change From Baseline in On-treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52	EQ-5D-5L is self-assessment questionnaire, consisting of 5 items covering 5 dimensions (mobility, self care, usual activities, pain/discomfort and anxiety/depression). Each dimension is measured by 5-point Likert scale (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Each of these 5 figure health states were converted to a single index score by applying country-specific value set formula that attaches weights to dimensions and levels. Range for EQ-5D-5L index score is -0.594 (worst health) to 1 (full health state). Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was latest non-missing pre-dose assessment on or before randomization date.	Baseline (Pre-dose on Day 1) and Week 52
Secondary	Change From Baseline in On-treatment EQ Visual Analogue Scale (EQ-VAS) at Week 52	The EQ VAS records the respondent's self-rated health on a vertical VAS, ranging from 0 to 100, where 0 represents the worst imaginable health and 100 represents the best imaginable health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.	Baseline (Pre-dose on Day 1) and Week 52
Secondary	Change From Baseline in On-treatment Chronic Kidney Disease- Anemia Symptoms Questionnaire (CKD-AQ) at Weeks 8, 12, 28, 52	CKD-AQ is 21-item patient reported outcome measure assessing symptoms and symptom impact in participants with anemia associated with CKD. It had 3 domains: 1.Tired/Low Energy (LE)/Weak scale consisting of 10 items; 2.Chest Pain (CP)/Shortness of Breath (SOB) scale consisting of 4 items; and 3.Cognitive (Cog) scale consisting of 3 items. The 4 CKD-AQ single items are: shortness of breath, no activity; severity-short breath (S-SB), resting; difficulty standing (diff. std.)for long time (LT) and difficulty sleeping (diff sleep). Single-item were recorded based on a 0-100 scoring with 0=worst possible and 100=best possible score. Three domains scores were calculated as average of items in each domain and ranged from 0-100 where 0=worst possible and 100=best possible score. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.	Baseline (Day 1) and Weeks 8, 12, 28, 52
Secondary	Change From Baseline in On-treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52	The PGI-S is a 1-item questionnaire designed to assess participant's impression of disease severity on a 5-point disease severity scale (0=absent, 1=mild, 2=moderate, 3=severe, or 4=very severe). A higher score indicated more disease severity. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.	Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary	Change From Baseline in Post-randomization Estimated Glomerular Filtration Rate (eGFR) at Week 52	Blood samples were collected to analyze estimated glomerular filtration rate. Change from Baseline was calculated as post-Baseline visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.	Baseline (Pre-dose on Day 1) and Week 52