Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease (CKD), Not on Dialysis

Anemia Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Roxadustat for the Treatment of Anemia in Chronic Kidney Disease Patients Not on Dialysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02174627
• Other study ID #: D5740C00001
• Status: Completed
• Phase: Phase 3
• Start date: June 26, 2014
• Est. completion date: October 4, 2018

Study information

• Verified date: November 2019
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the safety and efficacy of roxadustat for treatment of anemia in patients with chronic kidney disease not on dialysis

Description:

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study in anemic patients with Stage 3, 4 or 5 chronic kidney disease (CKD) who are not on dialysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2781
• Est. completion date: October 4, 2018
• Est. primary completion date: October 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures.

2. Age =18 years at screening visit 1

3. eGFR <60 mL/min/1.73 m2, (calculated by central lab) corresponding to stage 3, 4 or 5CKD according to the Kidney Disease Outcomes Quality Initiative (KDOQI), not receiving dialysis

4. Mean of 2 most recent central laboratory Hb values during the screening period, obtained at least 7 days apart, must be <10.0 g/dL

5. Ferritin =50 ng/mL at randomization (obtained from screening visit)

6. TSAT =15 % at randomization (obtained from screening visit)

7. Serum folate level = lower limit of normal (LLN) at randomization (obtained from screening visit)

8. Serum vitamin B12 level =LLN at randomization (obtained from screening visit)

9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3 x upper limit of normal (ULN) and total bilirubin (Tbili) =1.5 x ULN at randomization (obtained from screening visit)

10. Body weight 45 to 160 kg

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)

2. Previous randomization in the present study

3. Any erythropoietin analogue treatment within 6 weeks of randomization

4. New York Heart Association Class III or IV congestive heart failure at enrollment

5. Myocardial infarction (MI), acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization

6. History of chronic liver disease (e.g., chronic infectious hepatitis, chronic auto- immune liver disease, cirrhosis or fibrosis of the liver)

7. Known hereditary hematologic disease such as thalassemia, sickle cell anemia, a history of pure red cell aplasia or other known causes for anemia other than CKD

8. Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis)

9. Diagnosis or suspicion (e.g. complex kidney cyst of Bosniak Category IIF, III or IV) of renal cell carcinoma on renal ultrasound (or other imaging procedure e.g. CT scan or MRI) conducted at screening or within 12 weeks prior to randomization

10. Systolic BP =160 mmHg or diastolic BP =95 mmHg (confirmed by repeated measurement), within 2 weeks prior to randomization. Patients may be rescreened once BP controlled

11. History of prostate cancer, breast cancer or any other malignancy, except the following: cancers determined to be cured or in remission for =5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps

12. Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibody (anti-HCV Ab)

13. Chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ankylosing spondylitis, psoriatic arthritis or inflammatory bowel disease that is determined to be the principal cause of anemia

14. Known hemosiderosis, hemochromatosis or hypercoagulable condition

15. Any prior organ transplant or a scheduled organ transplantation date

16. Any red blood cell transfusion (RBC) during the screening period

17. Any current condition leading to active significant blood loss

18. Any treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI)

19. Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within at least 1 month of the first administration of IP in this study. (Note: patients consented and screened, but not randomized in this study or a previous study are not excluded)

20. History of alcohol or drug abuse within 2 years prior to randomization

21. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence

22. Pregnant or breastfeeding females

23. Known allergy to the investigational product or any of its ingredients

24. Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound efficacy or safety assessment or may interfere with study participation

Related Conditions & MeSH terms

• Anemia
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Roxadustat
The initial study drug dose is 70 mg three times a week (TIW). The dose is subsequently adjusted to achieve and maintain Hb 11±1 g/dL.
• Placebo
The initial study drug dose is 70 mg three times a week (TIW). The dose is subsequently adjusted to achieve and maintain Hb 11±1 g/dL.

Locations

Country	Name	City	State
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Capital Federal
Argentina	Research Site	Ciudad Autónoma de Bs. As.
Argentina	Research Site	Ciudadela
Argentina	Research Site	La Plata
Argentina	Research Site	La Plata
Argentina	Research Site	Lanus
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Munro
Argentina	Research Site	Ramos Mejía
Argentina	Research Site	Rosario
Argentina	Research Site	Rosario
Argentina	Research Site	San Isidro
Argentina	Research Site	San Miguel de Tucuman
Argentina	Research Site	Santa Rosa
Brazil	Research Site	Curitiba
Brazil	Research Site	Curitiba
Brazil	Research Site	Curitiba
Brazil	Research Site	Feira de Santana
Brazil	Research Site	Fortaleza
Brazil	Research Site	Fortaleza
Brazil	Research Site	Fortaleza
Brazil	Research Site	Goiânia
Brazil	Research Site	Joinville
Brazil	Research Site	Juiz de Fora
Brazil	Research Site	Maringa
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Sao Bernardo do Campo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Bulgaria	Research Site	Botevgrad
Bulgaria	Research Site	Dupnitsa
Bulgaria	Research Site	Gotse Delchev
Bulgaria	Research Site	Haskovo
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Samokov
Bulgaria	Research Site	Sandanski
Bulgaria	Research Site	Silistra
Bulgaria	Research Site	Sliven
Bulgaria	Research Site	Smolyan
Bulgaria	Research Site	Yambol
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Gatineau	Quebec
Canada	Research Site	Greenfield Park	Quebec
Canada	Research Site	Kamloops	British Columbia
Canada	Research Site	Kitchener	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	New Westminster	British Columbia
Canada	Research Site	Oakville	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Saint John	New Brunswick
Canada	Research Site	Scarborough	Ontario
Canada	Research Site	Sydney	Nova Scotia
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Whitby	Ontario
Canada	Research Site	Winnipeg	Manitoba
Colombia	Research Site	Cali
Colombia	Research Site	Chia
Colombia	Research Site	Medellin
Colombia	Research Site	Zipaquira
Czechia	Research Site	Brno
Czechia	Research Site	Havlickuv Brod
Czechia	Research Site	Ivancice
Czechia	Research Site	Praha
Czechia	Research Site	Rychnov nad Kneznou
Czechia	Research Site	Slany
Czechia	Research Site	Slavkov u Brna
Czechia	Research Site	Sumperk
Czechia	Research Site	Usti nad Labem
Czechia	Research Site	Usti nad Orlici
Germany	Research Site	Berlin
Germany	Research Site	Cloppenburg
Germany	Research Site	Köln
Hungary	Research Site	Ajka
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Gyula
Hungary	Research Site	Hatvan
Hungary	Research Site	Kecskemét
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Pécs
Hungary	Research Site	Polgár
Hungary	Research Site	Salgótarján
Hungary	Research Site	Siófok
Hungary	Research Site	Tatabánya
Hungary	Research Site	Velence
India	Research Site	Ahmedabad
India	Research Site	Bangalore
India	Research Site	Bangalore
India	Research Site	Bangalore
India	Research Site	Chennai
India	Research Site	Ghaziabad NCR
India	Research Site	Hyderabad
India	Research Site	Hyderabad
India	Research Site	Kolkatta
India	Research Site	Lucknow
India	Research Site	Maharashtra
India	Research Site	Mumbai
India	Research Site	Mysore
India	Research Site	Nagpur
India	Research Site	Nagpur
India	Research Site	Nagpur
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	Pune
India	Research Site	Vijayawada
India	Research Site	Vijayawada
India	Research Site	Vishakhapatnam
Korea, Republic of	Research Site	Ansan-si
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Daejeon
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Uijeongbu-si
Malaysia	Research Site	George Town
Malaysia	Research Site	Kubang Kerian
Malaysia	Research Site	Putrajaya
Malaysia	Research Site	Taiping
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Culiacán
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	México
Mexico	Research Site	Minatitlán
Mexico	Research Site	Veracruz
Mexico	Research Site	Xalapa
Peru	Research Site	Bellavista
Peru	Research Site	Ica
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Trujillo
Philippines	Research Site	Cebu City
Philippines	Research Site	Iloilo
Philippines	Research Site	Iloilo City
Philippines	Research Site	Quezon City
Poland	Research Site	Ciechanów
Poland	Research Site	Konskie
Poland	Research Site	Lódz
Poland	Research Site	Poznan
Poland	Research Site	Sochaczew
Poland	Research Site	Tczew
Puerto Rico	Research Site	Cidra
Puerto Rico	Research Site	Rio Grande
Puerto Rico	Research Site	Rio Piedras
Puerto Rico	Research Site	San Juan
Puerto Rico	Research Site	San Juan
Puerto Rico	Research Site	San Juan
Puerto Rico	Research Site	San Juan
Puerto Rico	Research Site	Toa Baja
Romania	Research Site	Arad
Romania	Research Site	Bucuresti
Romania	Research Site	Bucuresti
Romania	Research Site	Targu Mures
Romania	Research Site	Timisoara
Russian Federation	Research Site	Arkhangelsk
Russian Federation	Research Site	Barnaul
Russian Federation	Research Site	Irkutsk
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Krasnoyarsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Nizhniy Novgorod
Russian Federation	Research Site	Nizhny Novgorod
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Ufa
Russian Federation	Research Site	Ufa
Russian Federation	Research Site	Ufa
Russian Federation	Research Site	Volgograd
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Kosice
Slovakia	Research Site	Kralovsky Chlmec
Slovakia	Research Site	Nove Zamky
Slovakia	Research Site	Zvolen
Spain	Research Site	Almería
Spain	Research Site	Málaga
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Spain	Research Site	Valencia
Spain	Research Site	Valencia
Taiwan	Research Site	Kaohsiung City
Taiwan	Research Site	Keelung
Taiwan	Research Site	New Taipei
Taiwan	Research Site	New Taipei
Taiwan	Research Site	New Taipei
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	TaoYuan
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Khon Kaen
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Antalya
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Ukraine	Research Site	Chernivtsi
Ukraine	Research Site	Dnipro
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Khmelnytsky
Ukraine	Research Site	Kirovograd
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lutsk
Ukraine	Research Site	Lviv
Ukraine	Research Site	Odesa
Ukraine	Research Site	Rivne
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhya
Ukraine	Research Site	Zaporizhzhya
Ukraine	Research Site	Zaporizhzhya
Ukraine	Research Site	Zaporizhzhya
United States	Research Site	Arvada	Colorado
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aventura	Florida
United States	Research Site	Bakersfield	California
United States	Research Site	Bethlehem	Pennsylvania
United States	Research Site	Birmingham	Alabama
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbia	South Carolina
United States	Research Site	Columbus	Ohio
United States	Research Site	Columbus	Georgia
United States	Research Site	Columbus	Georgia
United States	Research Site	Coral Gables	Florida
United States	Research Site	Coral Springs	Florida
United States	Research Site	Corpus Christi	Texas
United States	Research Site	Cypress	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Edgewater	Florida
United States	Research Site	El Centro	California
United States	Research Site	Escondido	California
United States	Research Site	Flushing	New York
United States	Research Site	Glendale	California
United States	Research Site	Great Neck	New York
United States	Research Site	Greenbelt	Maryland
United States	Research Site	Gulfport	Mississippi
United States	Research Site	High Point	North Carolina
United States	Research Site	Hollywood	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Huntsville	Alabama
United States	Research Site	Jacksonville	North Carolina
United States	Research Site	Joliet	Illinois
United States	Research Site	Kansas City	Missouri
United States	Research Site	Kissimmee	Florida
United States	Research Site	Knoxville	Tennessee
United States	Research Site	La Grange	Illinois
United States	Research Site	Lansdale	Pennsylvania
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lauderdale Lakes	Florida
United States	Research Site	Long Beach	California
United States	Research Site	Long Beach	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Lufkin	Texas
United States	Research Site	Lynwood	California
United States	Research Site	Metairie	Louisiana
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	National City	California
United States	Research Site	New Bern	North Carolina
United States	Research Site	Norfolk	Virginia
United States	Research Site	Northridge	California
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orange	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Port Charlotte	Florida
United States	Research Site	Port Huron	Michigan
United States	Research Site	Providence	Rhode Island
United States	Research Site	Providence	Rhode Island
United States	Research Site	Reno	Nevada
United States	Research Site	Rochester	New Hampshire
United States	Research Site	Rockport	Maine
United States	Research Site	Rockville	Maryland
United States	Research Site	Sacramento	California
United States	Research Site	Sacramento	California
United States	Research Site	Saint George	Utah
United States	Research Site	Salem	Virginia
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	San Dimas	California
United States	Research Site	San Francisco	California
United States	Research Site	San Luis Obispo	California
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Tampa	Florida
United States	Research Site	Uniontown	Pennsylvania
United States	Research Site	Upland	California
United States	Research Site	Waterbury	Connecticut
United States	Research Site	Wilmington	North Carolina
United States	Research Site	Woodbridge	Virginia
Vietnam	Research Site	Can Tho
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh City
Vietnam	Research Site	Hochiminh
Vietnam	Research Site	Hochiminh
Vietnam	Research Site	Hue

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	FibroGen

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Brazil,  Bulgaria,  Canada,  Colombia,  Czechia,  Germany,  Hungary,  India,  Korea, Republic of,  Malaysia,  Mexico,  Peru,  Philippines,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Slovakia,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52	Baseline Hb was defined as the mean of the last 3 central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to mean value from Week 28 to Week 52 was analyzed using a missing at random (MAR) based multiple imputation analysis of covariance (ANCOVA) model with baseline Hb, baseline estimated glomerular filtration rate (eGFR), cardiovascular (CV) history, geographic region and treatment group as fixed effect covariates. The adjusted least squares (LS) mean estimates of change from baseline to mean during Week 28 to Week 52 are presented.	Baseline (Day 1, Week 0) and Week 28 to Week 52.
Secondary	Percentage of Participants With Hb Response During the First 24 Weeks of Treatment	Hb response was defined as: Hb = 11.0 g/dL and Hb increase from baseline by = 1.0 g/dL for participants with baseline Hb > 8.0 g/dL; or; Hb increase from baseline by = 2.0 g/dL, for participants with baseline Hb = 8.0 g/dL at 2 consecutive visits (with available data) separated at least 5 days during the first 24 weeks of treatment without having received rescue therapy (red blood cell [RBC] transfusion, erythropoietin analogue, or intravenous [IV] iron) prior to Hb response. The percentage of participants with an Hb response during the first 24 weeks of treatment is presented.	Baseline (Day 1, Week 0) up to Week 24.
Secondary	Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52 in Participants With Baseline High Sensitivity C-Reactive Protein (hsCRP) Greater Than the Upper Limit of Normal (ULN)	Baseline hsCRP was quantified from stored biomarker samples obtained at randomization. Baseline Hb was defined as the mean of the last 3 central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to mean value during Week 28 to Week 52 was analyzed using a MAR based multiple imputation ANCOVA model with baseline Hb, baseline eGFR, CV history, geographic region and treatment group as fixed effect covariates. The adjusted LS mean estimates of change from baseline in participants with baseline hsCRP >ULN to mean during Week 28 to Week 52 are presented.	Baseline (Day 1, Week 0) and Week 28 to Week 52.
Secondary	Proportion of Total Time of Interpolated Hb Values Greater Than or Equal To 10 g/dL From Week 28 to Week 52	Proportion of total time of interpolated Hb values =10 g/dL was calculated as the time the linearly interpolated curve between measurements =10 g/dL divided by the time between measurements from Week 28 to Week 52. Proportion of total time was analyzed using an ANCOVA model with baseline Hb and baseline eGFR as covariates, and CV history, geographic region and treatment group as fixed effects. The adjusted LS mean estimates of change from Week 28 to Week 52 are presented.	Week 28 up to Week 52.
Secondary	Proportion of Total Time of Interpolated Hb Values Within the Interval of 10 to 12 g/dL From Week 28 to Week 52	Proportion of total time of interpolated Hb values within the interval of 10 to 12 g/dL was calculated as the time the linearly interpolated curve between measurements were within 10 to 12 g/dL divided by the time between measurements from Week 28 to Week 52. Proportion of total time was analyzed using an ANCOVA model with baseline Hb and baseline eGFR as covariates, and CV history, geographic region and treatment group as fixed effects. The adjusted LS mean estimates of change from Week 28 to Week 52 are presented.	Week 28 up to Week 52.
Secondary	Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24	Baseline LDL was defined as the last result obtained prior to randomization. Mean changes in LDL cholesterol from baseline to Week 24 was analyzed using an ANCOVA model with baseline LDL, baseline Hb and baseline eGFR as covariates, and CV history, geographic region and treatment group as fixed effects. The adjusted LS mean estimates of change from baseline to Week 24 are presented.	Baseline (Day 1, Week 0) and Week 24
Secondary	Time-To-First Instance of Receiving IV Iron, RBC Transfusion or Erythropoietin Analogue as Rescue Therapy	Time-to-first rescue therapy (IV iron, RBC transfusion or erythropoietin analogue) was calculated as (date of first rescue therapy, or date of censoring if no rescue therapy was taken) minus (date of first dose of IP) +1. Event rate was calculated as (number of participants with event) divided by (the total number of days at risk for event across all participants in given group divided by 365.25) multiplied by 100. The event rate is presented for participants with events.	Baseline (Day1, Week 0) up to End of Study (EOS) visit (4 weeks after the treatment period) (or up to date of first rescue therapy), with treatment duration up to 4 years.
Secondary	Time-To-First Instance of Receiving a RBC Transfusion As Rescue Therapy	Time-to-first RBC rescue therapy was calculated as (date of first RBC rescue therapy, or date of censoring if no rescue therapy was taken) minus (date of first dose of IP) +1. Event rate was calculated as (number of participants with event) divided by (the total number of days at risk for event across all participants in given group divided by 365.25) multiplied by 100. The event rate is presented for participants with events.	Baseline (Day1, Week 0) up to EOS visit (4 weeks after the treatment period) (or up to date of first RBC rescue therapy), with treatment duration up to 4 years.
Secondary	Mean Change From Baseline in Short Form 36 (SF-36) Vitality Sub-Score From Week 12 to Week 28	SF-36 is a Quality of Life (QoL) scale comprising 8 domains of health status: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health. Each domain score is on a scale from 0-100 (worst health possible to best health possible); higher scores indicate better health status. Mean change in SF-36 Vitality sub-score from baseline to mean from Week 12 to Week 28 was analyzed using a mixed model for repeated measures (MMRM) with terms for baseline score, treatment group, baseline Hb, baseline eGFR, CV history, geographic region, visit and treatment-by-visit interaction as fixed effects and participant as random effect. The adjusted LS mean estimates of change from baseline to mean score from Week 12 to Week 28 are presented.	Baseline (Day 1, Week 0) and Week 12 to Week 28.
Secondary	Annual Rate of eGFR Change From Baseline Prior to the Initiation of Dialysis or Kidney Transplant	Baseline eGFR was defined as the mean of all available central laboratory values prior to or at randomization. Rate of change in eGFR from baseline during the entire treatment period (in millilitres/minute/1.73 meters squared/years [mL/min/1.73m^2/years]) was estimated using a random effects model using all post-baseline eGFR values prior to initiation of dialysis/transplant. Baseline eGFR, baseline Hb, geographic region, CV history, treatment group and post-baseline eGFR measurement time were used as fixed effects and participant and time (years) as random effects, ie, random intercept and slope.	Baseline (Day1, Week 0) up to EOS visit (4 weeks after the treatment period), with treatment duration up to 4 years.
Secondary	Mean Change From Baseline in SF-36 Physical Functioning Sub-Score From Week 12 to Week 28	SF-36 is a QoL scale comprising 8 domains of health status: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health. Each domain score is on a scale from 0-100 (worst health possible to best health possible); higher scores indicate better health status. Mean change in SF-36 Physical Functioning sub-score from baseline to mean from Week 12 to Week 28 was analyzed using a MMRM with terms for baseline score, treatment group, baseline Hb, baseline eGFR, CV history, geographic region, visit and treatment-by-visit interaction as fixed effects and participant as random effect. The adjusted LS mean estimates of change from baseline to mean score from Week 12 to Week 28 are presented.	Baseline (Day 1, Week 0) and Week 12 to Week 28.

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