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

Anaemia Clinical Trial

Official title:

A Phase 3 Randomized, Open-label (Sponsor-blind), Active-controlled, Parallel-group, Multi-center, Event Driven Study in Dialysis Subjects With Anemia Associated With Chronic Kidney Disease to Evaluate the Safety and Efficacy of Daprodustat Compared to Recombinant Human Erythropoietin, Following a Switch From Erythropoietin-stimulating Agents

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02879305
• Other study ID #: 200807
• Secondary ID: 2016-000541-31
• Status: Completed
• Phase: Phase 3
• Start date: September 28, 2016
• Est. completion date: November 9, 2020

Study information

• Verified date: November 2021
• 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 participants with anemia associated with chronic kidney disease (CKD) to evaluate the safety and efficacy of daprodustat.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2964
• Est. completion date: November 9, 2020
• Est. primary completion date: November 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

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

• Erythropoietin-stimulating agents (ESAs): Use of any approved ESA for at least the 6 weeks prior to screening and between screening and randomization.

• Hgb concentration: On Week -8: Hgb 8 to 12 grams per deciliter (g/dL). On randomization (Day 1): Hgb 8 to 11 g/dL and receiving at least the minimum ESA dose. Hgb >11 g/dL to 11.5 g/dL and receiving greater than the minimum ESA dose.

• Dialysis: On dialysis >90 days prior to screening and continuing on the same mode of dialysis from screening (Week -8) through to randomization (Day 1).

• Frequency of Dialysis: Hemodialysis (HD) >=2 times/week and peritoneal dialysis (PD) >=5 times/week. Home hemodialysis >=2 times/week.

• Compliance with placebo [randomization (Day 1) only]: >=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 listed in the consent form and in this protocol.

Exclusion Criteria:

• 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 that would contraindicate the use of recombinant human erythropoietin (rhEPO).

• 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 QT 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 epoetin alfa 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).

• 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 serum 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 listed in the List of Highly Effective Methods for Avoiding Pregnancy.

• 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 rhEPO) or prevent understanding of the aims or investigational procedures or possible consequences of the study.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Daprodustat
Daprodustat dose is based on prior ESA dose, the dose is adjusted thereafter in order to achieve the target range.
• rhEPO
The initial ESA dose is based on converting the prior ESA dose to the nearest available study rhEPO dose and is administered IV. The dose is adjusted thereafter in order to achieve the target range.
• 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	Burzaco	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Evita	Buenos Aires
Argentina	GSK Investigational Site	Córdoba	Córdova
Argentina	GSK Investigational Site	Formosa
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Moron
Argentina	GSK Investigational Site	Pergamino	Buenos Aires
Argentina	GSK Investigational Site	Pilar	Buenos Aires
Argentina	GSK Investigational Site	San Miguel de Tucumán
Australia	GSK Investigational Site	Adelaide	South Australia
Australia	GSK Investigational Site	Birtinya	Queensland
Australia	GSK Investigational Site	Clayton	Victoria
Australia	GSK Investigational Site	Concord	New South Wales
Australia	GSK Investigational Site	Herston	Queensland
Australia	GSK Investigational Site	Kingswood	New South Wales
Australia	GSK Investigational Site	Kogarah	New South Wales
Australia	GSK Investigational Site	Liverpool	New South Wales
Australia	GSK Investigational Site	Melbourne	Victoria
Australia	GSK Investigational Site	Murdoch
Australia	GSK Investigational Site	Nedlands	Western Australia
Australia	GSK Investigational Site	St Albans	Victoria
Australia	GSK Investigational Site	St Leonards	New South Wales
Australia	GSK Investigational Site	Westmead	New South Wales
Australia	GSK Investigational Site	Wollongong	New South Wales
Australia	GSK Investigational Site	Woolloongabba	Queensland
Austria	GSK Investigational Site	Graz
Austria	GSK Investigational Site	St. Pölten
Austria	GSK Investigational Site	Wien
Austria	GSK Investigational Site	Wien
Belgium	GSK Investigational Site	Baudour
Belgium	GSK Investigational Site	Brugge
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Hasselt
Belgium	GSK Investigational Site	Ieper
Belgium	GSK Investigational Site	Leuven
Belgium	GSK Investigational Site	Liège
Belgium	GSK Investigational Site	Roeselare
Brazil	GSK Investigational Site	Belo Horizonte, Minas Gerais
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Feira de Santana
Brazil	GSK Investigational Site	Joinville	Santa Catarina
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
Brazil	GSK Investigational Site	Porto Alegre
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
Bulgaria	GSK Investigational Site	Blagoevgrad
Bulgaria	GSK Investigational Site	Dobrich
Bulgaria	GSK Investigational Site	Gabrovo
Bulgaria	GSK Investigational Site	Lom
Bulgaria	GSK Investigational Site	Lovech
Bulgaria	GSK Investigational Site	Montana
Bulgaria	GSK Investigational Site	Pazardzhik
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Ruse
Bulgaria	GSK Investigational Site	Smolyan
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Varna
Bulgaria	GSK Investigational Site	Veliko Tarnovo
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Czechia	GSK Investigational Site	Beroun
Czechia	GSK Investigational Site	Frýdek-mistek
Czechia	GSK Investigational Site	Ivancice
Czechia	GSK Investigational Site	Jilemnice
Czechia	GSK Investigational Site	Marianske Lazne
Czechia	GSK Investigational Site	Pardubice
Czechia	GSK Investigational Site	Praha 2
Czechia	GSK Investigational Site	Praha 4
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
Denmark	GSK Investigational Site	Svendborg
Estonia	GSK Investigational Site	Parnu
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tartu
France	GSK Investigational Site	Annonay
France	GSK Investigational Site	Bois-Guillaume
France	GSK Investigational Site	Bordeaux
France	GSK Investigational Site	Boulogne Billancourt
France	GSK Investigational Site	Caen Cedex 9
France	GSK Investigational Site	Mulhouse
France	GSK Investigational Site	Poitiers
France	GSK Investigational Site	Reims
France	GSK Investigational Site	Tours cedex 9
Germany	GSK Investigational Site	Bad Koenig	Hessen
Germany	GSK Investigational Site	Cloppenburg	Niedersachsen
Germany	GSK Investigational Site	Dieburg
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Freiburg
Germany	GSK Investigational Site	Kaiserslautern	Rheinland-Pfalz
Germany	GSK Investigational Site	Kiel	Schleswig-Holstein
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Minden
Germany	GSK Investigational Site	Rostock	Mecklenburg-Vorpommern
Germany	GSK Investigational Site	Wiesbaden	Hessen
Greece	GSK Investigational Site	Alexandroupolis
Greece	GSK Investigational Site	Arta
Greece	GSK Investigational Site	Athens
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	Patras
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Egri
Hungary	GSK Investigational Site	Esztergom
Hungary	GSK Investigational Site	Kecskemet
Hungary	GSK Investigational Site	Miskolc
Hungary	GSK Investigational Site	Pécs
Hungary	GSK Investigational Site	Pécs
Hungary	GSK Investigational Site	Szigetvar
India	GSK Investigational Site	Ahmedabad
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Calicut
India	GSK Investigational Site	Chennai
India	GSK Investigational Site	Chennai, Tamil Nadu
India	GSK Investigational Site	Delhi
India	GSK Investigational Site	Gurgaon
India	GSK Investigational Site	Hyderabad
India	GSK Investigational Site	Jaipur
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	Pune
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Secunderabad
India	GSK Investigational Site	Trivandrum
Italy	GSK Investigational Site	Bergamo	Lombardia
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	Monza	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 Calabria	Calabria
Italy	GSK Investigational Site	Seriate	Lombardia
Italy	GSK Investigational Site	Torino	Piemonte
Korea, Republic of	GSK Investigational Site	Anyang-Si, Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Bucheon-si,
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Daegu-si
Korea, Republic of	GSK Investigational Site	Daejeon
Korea, Republic of	GSK Investigational Site	Goyang-si
Korea, Republic of	GSK Investigational Site	Goyang-si
Korea, Republic of	GSK Investigational Site	Goyang-si, Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Incheon
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	Uijeongbu-si
Korea, Republic of	GSK Investigational Site	Wonju-si
Malaysia	GSK Investigational Site	Batu Caves
Malaysia	GSK Investigational Site	Ipoh
Malaysia	GSK Investigational Site	Johor Bahru
Malaysia	GSK Investigational Site	Kuala Lumpur
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 México	Estado De México
Mexico	GSK Investigational Site	Cuautitlan Izcalli	Estado De México
Mexico	GSK Investigational Site	Durango.	Durango
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Merida	Yucatán
Mexico	GSK Investigational Site	México, D.F.
Mexico	GSK Investigational Site	Queretaro	Querétaro
Mexico	GSK Investigational Site	Saltillo	Coahuila
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	Hamilton
New Zealand	GSK Investigational Site	Hastings
New Zealand	GSK Investigational Site	Otahuhu
Norway	GSK Investigational Site	Oslo
Norway	GSK Investigational Site	Stavanger
Poland	GSK Investigational Site	Biala Podlaska
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Grojec
Poland	GSK Investigational Site	Kielce
Poland	GSK Investigational Site	Kolo
Poland	GSK Investigational Site	Kolobrzeg
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Olkusz
Poland	GSK Investigational Site	Pruszkow
Poland	GSK Investigational Site	Tomaszow Mazowiecki
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Zary
Portugal	GSK Investigational Site	Amadora
Portugal	GSK Investigational Site	Corroios.
Portugal	GSK Investigational Site	Covilhã
Portugal	GSK Investigational Site	Forte Da Casa
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Mirandela
Portugal	GSK Investigational Site	Portimão
Portugal	GSK Investigational Site	Vila Franca de Xira
Portugal	GSK Investigational Site	Vila Real (Lordelo)
Romania	GSK Investigational Site	Arad
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Resita
Romania	GSK Investigational Site	Targu-Jiu
Russian Federation	GSK Investigational Site	Irkutsk
Russian Federation	GSK Investigational Site	Krasnodar
Russian Federation	GSK Investigational Site	Mytischi
Russian Federation	GSK Investigational Site	Nizhniy Novgorod
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Omsk
Russian Federation	GSK Investigational Site	Orenburg
Russian Federation	GSK Investigational Site	Penza
Russian Federation	GSK Investigational Site	St-Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
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
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Cape Town.
Spain	GSK Investigational Site	Alcala de Henares
Spain	GSK Investigational Site	Aranda de Duero
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Ciudad Real
Spain	GSK Investigational Site	Girona
Spain	GSK Investigational Site	Guadalajara
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Majadahonda	Madrid
Spain	GSK Investigational Site	Málaga
Spain	GSK Investigational Site	Manises (Valencia)
Spain	GSK Investigational Site	Mollet del Valles
Spain	GSK Investigational Site	Palma de Mallorca
Spain	GSK Investigational Site	Sabadell
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Valladolid
Sweden	GSK Investigational Site	Örebro
Sweden	GSK Investigational Site	Stockholm
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	New Taipei City
Taiwan	GSK Investigational Site	New Taipei City
Taiwan	GSK Investigational Site	Tainan
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taoyuan Hsien
Taiwan	GSK Investigational Site	Zhongzheng Dist., Taipei
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	Kayseri
Ukraine	GSK Investigational Site	Chernihiv
Ukraine	GSK Investigational Site	Chernivtsi
Ukraine	GSK Investigational Site	Ivano-Frankivsk
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	Mykolaiv
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	Derby
United Kingdom	GSK Investigational Site	Doncaster
United Kingdom	GSK Investigational Site	Dundee
United Kingdom	GSK Investigational Site	Fife
United Kingdom	GSK Investigational Site	Glasgow
United Kingdom	GSK Investigational Site	Hull
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
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 States	GSK Investigational Site	Alexandria	Virginia
United States	GSK Investigational Site	Anaheim	California
United States	GSK Investigational Site	Anderson	South Carolina
United States	GSK Investigational Site	Asheville	North Carolina
United States	GSK Investigational Site	Augusta	Georgia
United States	GSK Investigational Site	Augusta	Georgia
United States	GSK Investigational Site	Aventura	Florida
United States	GSK Investigational Site	Bakersfield	California
United States	GSK Investigational Site	Bakersfield	California
United States	GSK Investigational Site	Baton Rouge	Louisiana
United States	GSK Investigational Site	Baton Rouge	Louisiana
United States	GSK Investigational Site	Beaumont	Texas
United States	GSK Investigational Site	Bethlehem	Pennsylvania
United States	GSK Investigational Site	Beverly Hills	California
United States	GSK Investigational Site	Bluefield	West Virginia
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	Cerritos	California
United States	GSK Investigational Site	Charleston	South Carolina
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	Clyde	North 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	Crystal Lake	Illinois
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	Fairfield	California
United States	GSK Investigational Site	Florissant	Missouri
United States	GSK Investigational Site	Flushing	New York
United States	GSK Investigational Site	Fort Wayne	Indiana
United States	GSK Investigational Site	Fountain Valley	California
United States	GSK Investigational Site	Gallup	New Mexico
United States	GSK Investigational Site	Glendale	California
United States	GSK Investigational Site	Granada Hills	California
United States	GSK Investigational Site	Greenbelt	Maryland
United States	GSK Investigational Site	Gulfport	Mississippi
United States	GSK Investigational Site	Hacienda Heights	California
United States	GSK Investigational Site	Hampton	Virginia
United States	GSK Investigational Site	Hollywood	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	Huntsville	Alabama
United States	GSK Investigational Site	Iowa City	Iowa
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	Kansas City	Missouri
United States	GSK Investigational Site	Knoxville	Tennessee
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	Lakewood	California
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Lauderdale Lakes	Florida
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Long Beach	California
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	Lynwood	California
United States	GSK Investigational Site	Meridian	Idaho
United States	GSK Investigational Site	Merrillville	Indiana
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	Michigan City	Indiana
United States	GSK Investigational Site	Middlebury	Connecticut
United States	GSK Investigational Site	Mineola	New York
United States	GSK Investigational Site	Montebello	California
United States	GSK Investigational Site	Monterey Park	California
United States	GSK Investigational Site	Moreno Valley	California
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Norco	California
United States	GSK Investigational Site	Northridge	California
United States	GSK Investigational Site	Ocala	Florida
United States	GSK Investigational Site	Ontario	California
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Pine Bluff	Arkansas
United States	GSK Investigational Site	Pontiac	Michigan
United States	GSK Investigational Site	Port Charlotte	Florida
United States	GSK Investigational Site	Portsmouth	New Hampshire
United States	GSK Investigational Site	Providence	Rhode Island
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	Roseburg	Oregon
United States	GSK Investigational Site	Roseville	Michigan
United States	GSK Investigational Site	Sacramento	California
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	Santa Clarita	California
United States	GSK Investigational Site	Shorewood	Wisconsin
United States	GSK Investigational Site	Simi Valley	California
United States	GSK Investigational Site	Spring Hill	Florida
United States	GSK Investigational Site	Sumter	South Carolina
United States	GSK Investigational Site	Takoma Park	Maryland
United States	GSK Investigational Site	Tarzana	California
United States	GSK Investigational Site	Tupelo	Mississippi
United States	GSK Investigational Site	Washington	District of Columbia
United States	GSK Investigational Site	Whittier	California
United States	GSK Investigational Site	Whittier	California
United States	GSK Investigational Site	Winston-Salem	North Carolina
United States	GSK Investigational Site	Winston-Salem	North Carolina
United States	GSK Investigational Site	Winter Park	Florida
United States	GSK Investigational Site	Yonkers	New York
United States	GSK Investigational Site	Yorba Linda	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

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

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 the 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, dialysis type 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 by [*] 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 3.9 person-years for CV follow-up time period
Primary	Mean Change From Baseline in Hemoglobin (Hgb) Levels During Evaluation Period (Week 28 to Week 52)	Blood samples were collected from participants for hemoglobin measurements. Hemoglobin during the evaluation period was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis, missing post-Baseline hemoglobin 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.	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, dialysis type 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 3.9 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, dialysis type 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 3.9 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, dialysis type 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 3.9 person-years for CV follow-up time period
Secondary	Mean Average Monthly On-treatment IV Iron Dose Per Participant	Average monthly IV iron dose (milligrams) per participant from Day 1 to Week 52 was determined by calculating the total IV iron dose per participant from treatment start date + 1 to the earliest of (Week 52 visit date, first blood (red blood cell [RBC] or whole blood) transfusion date, and treatment stop date + 1 day) which corresponds to the time while the participant was on randomized treatment and before receiving a blood transfusion. This total IV iron dose was divided by (the number of days from treatment start date + 1 to the earliest of (Week 52 visit date, first blood transfusion date (RBC or whole blood), and treatment stop date +1) / 30.4375 days). This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.	Day 1 to Week 52
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, dialysis type 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 for follow-up time period.	Up to 3.9 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, dialysis type 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 3.9 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, dialysis type 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 3.9 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, dialysis type 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 3.9 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 3.9 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, dialysis type 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 3.9 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) 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, dialysis type 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 3.9 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 eCRF with hospitalization duration of >=24 hours and admission date within 30days following previous discharge date of all-cause hospitalization event, where previous hospitalization was >=24 hours. Time to first occurrence of all-cause hospital re-admission within 30days was analyzed using Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date)+1. Incidence rate per 100person 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 3.9 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, dialysis type 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 3.9 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, dialysis type 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 3.9 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, dialysis type 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 3.9 person-years for CV follow-up time period
Secondary	Change From Baseline in Post-randomization Hemoglobin Levels at Week 52	Blood samples were collected from participants for hemoglobin measurements. 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 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, dialysis type, region, Baseline hemoglobin and Baseline hemoglobin 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. Hemoglobin 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 Hemoglobin 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 Hemoglobin 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 Hemoglobin 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 (3.9 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 (3.9 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 semi-supine or seated position in the dialysis chair 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 + dialysis type + 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 semi-supine or seated position in the dialysis chair 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. This analysis was carried out by using ANCOVA model with terms for treatment group, dialysis type, region and Baseline value. Data for post-dialysis BP measurements have been presented.	Baseline (Week -4) and 45.1 months
Secondary	Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years	BP exacerbation was defined (based on post-dialysis) 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, dialysis type 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 study (3.9 person-years for follow-up time period)
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 study (3.9 person-years for follow-up time period)
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 45.1 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 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 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, general health, mental health, role-emotional (role limitations caused by emotional problems), role-physical (role limitations caused by physical problems), social functioning (Social fun), physical functioning (Phy. fun) 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 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-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 EuroQol 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 health one can imagine and 100 represents the best health one can imagine. 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 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 worse outcome. 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