Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not Requiring Dialysis

NCT ID: NCT01887600

Last Updated: 2024-11-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

594 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-03

Study Completion Date

2017-11-01

Brief Summary

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This study was conducted to treat anemia in patients with chronic kidney disease. Anemia is a reduced number of red blood cells or hemoglobin. Hemoglobin is important for the transport of oxygen in your blood. The purpose of the study was to see if Roxadustat is both effective and safe as a treatment for anemia in patients with chronic kidney disease.

Detailed Description

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The study consisted of three study periods as follows:

* Screening period: up to 6 weeks
* Treatment period: minimum 52 weeks (primary treatment period) up to a maximum of 104 weeks (extended treatment period)
* Post-Treatment Follow-Up period: 4 weeks

Conditions

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Anemia in Chronic Kidney Disease in Non-dialysis Patients

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Roxadustat

Participants received roxadustat according to the tiered weight-based approach, with starting doses of 70 mg given thrice weekly (TIW) to participants weighing up to 70 kg and 100 mg given TIW to participants weighing more than 70 kg. Dose-titration was performed based upon regular measurement of Hb levels until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL. Participants received roxadustat for at least 52 weeks up to a maximum of 104 weeks.

Group Type EXPERIMENTAL

Roxadustat

Intervention Type DRUG

Roxadustat was administered initially according to the tiered weight-based dosing, where participants with weight from ≥ 45 to ≤ 70 kg received 70 mg and participants with \> 70 to ≤ 160 kg received 100 mg of roxadustat. Dose-titration based upon regular measurement of Hb levels was performed until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL.

Placebo

Participants received matching placebo according to the tiered weight-based approach, with starting doses of 70 mg given thrice weekly (TIW) to participants weighing up to 70 kg and 100 mg given TIW to participants weighing more than 70 kg. Dose-titration was performed based upon regular measurement of Hb levels until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL. Participants received matching placebo for at least 52 weeks up to a maximum of 104 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo was administered initially according to the tiered weight-based dosing, where participants with weight from ≥ 45 to ≤ 70 kg received 70 mg and participants with \> 70 to ≤ 160 kg received 100 mg of roxadustat. Dose-titration based upon regular measurement of Hb levels was performed until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL.

Interventions

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Roxadustat

Roxadustat was administered initially according to the tiered weight-based dosing, where participants with weight from ≥ 45 to ≤ 70 kg received 70 mg and participants with \> 70 to ≤ 160 kg received 100 mg of roxadustat. Dose-titration based upon regular measurement of Hb levels was performed until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL.

Intervention Type DRUG

Placebo

Placebo was administered initially according to the tiered weight-based dosing, where participants with weight from ≥ 45 to ≤ 70 kg received 70 mg and participants with \> 70 to ≤ 160 kg received 100 mg of roxadustat. Dose-titration based upon regular measurement of Hb levels was performed until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL.

Intervention Type DRUG

Other Intervention Names

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ASP1517 FG-4592

Eligibility Criteria

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Inclusion Criteria

* Participant has a diagnosis of chronic kidney disease, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4 or 5, not receiving dialysis; with an Estimated Glomerular Filtration Rate (eGFR) \<60 mL/min/1.73 m\^2 estimated using the abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) equation.
* The mean of the Participant's three most recent Hb values during the Screening period, obtained at least 4 days apart, must be less than or equal to 10.0 g/dL, with a difference of less than or equal to 1.0 g/dL between the highest and the lowest values. The last Hb value must be within 10 days prior to randomization.
* Participant has a ferritin level greater than or equal to 30 ng/mL (greater than or equal to 67.4 pmol/L) at screening.
* Participant has a transferrin saturation (TSAT) level greater than or equal to 5% at screening.
* Participant has a serum folate level greater than or equal to lower limit of normal at screening.
* Participant has a serum vitamin B12 level greater than or equal to lower limit of normal at screening.
* Participant's alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels are less than or equal to 3 x upper limit of normal (ULN), and total bilirubin (TBL) is less than or equal to 1.5 x ULN.
* Participant's body weight is 45.0 kg up to a maximum of 160.0 kg.

Exclusion Criteria

* Participant has received any ESA treatment within 12 weeks prior to randomization.
* Participant has had more than one dose of IV iron within 12 weeks prior to randomization.
* Participant has received a RBC transfusion within 8 weeks prior to randomization.
* Participant has a known history of myelodysplastic syndrome or multiple myeloma.
* Participant has a known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than CKD.
* Participant has a known hemosiderosis, hemochromatosis, coagulation disorder, or hypercoagulable condition.
* Participant has chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission.
* Participant is anticipated to have elective surgery that is expected to lead to significant blood loss or anticipated elective coronary revascularization.
* Participant has active or chronic gastrointestinal bleeding.
* Participant has received any prior treatment with roxadustat or a hypoxia-inducible factor Prolyl Hydroxylase Inhibitor (HIF-PHI).
* Participant has been treated with iron-chelating agents within 4 weeks prior to randomization.
* Participant has a history of chronic liver disease (e.g., cirrhosis or fibrosis of the liver)
* Participant has a known New York Heart Association Class III or Intravenous (IV) congestive heart failure.
* Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (e.g., pulmonary embolism) within 12 weeks prior to randomization.
* Uncontrolled hypertension or two or more blood pressure (BP) values of systolic BP (SBP) greater than or equal to 160 mmHg or diastolic BP (DBP) greater than or equal to 95 mmHg confirmed by repeat measurement within 2 weeks prior to randomization.
* Participant has a diagnosis or suspicion (e.g., complex kidney cyst of Bosniak Category 2F or higher) of renal cell carcinoma on renal ultrasound within 12 weeks prior to randomization.
* Participant has a history of malignancy, except the following: cancers determined to be cured or in remission for greater than or equal to 5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps.
* Participant is positive for any of the following: Human Immunodeficiency Virus (HIV); hepatitis B surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab).
* Participant has an active clinically significant infection manifested by White Blood Count (WBC) \> ULN, and/or fever, in conjunction with clinical signs or symptoms of infection within one week prior to randomization.
* Participant has a known untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration and retinal vein occlusion.
* Participant has had any prior organ transplant (that has not been explanted) or a scheduled organ transplantation.
* Participant has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives or limit set by national law, whichever is longer, prior to the initiation of Screening.
* Participant has an anticipated use of dapsone in any dose amount or chronic use of acetaminophen (paracetamol) \> 2.0 g/day during the treatment or follow-up period of the study.
* Participant has a history of alcohol or drug abuse within 2 years prior to randomization.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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FibroGen

INDUSTRY

Sponsor Role collaborator

Astellas Pharma Europe B.V.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Monitor

Role: STUDY_CHAIR

Astellas Pharma Europe B.V.

Locations

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Site BY37503

Brest, , Belarus

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Site BY37501

Grodno, , Belarus

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Site BY37504

Homyel, , Belarus

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Site BY37506

Minsk, , Belarus

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Site BY37507

Minsk, , Belarus

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Site BY37505

Minsk, , Belarus

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Site BY37502

Vitebsk, , Belarus

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Site BE32004

Brussels, Flemish Brabant, Belgium

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Site BE32002

Antwerp, , Belgium

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Site BE32012

Baudour, , Belgium

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Site BE32017

Bonheiden, , Belgium

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Site BE32014

Ieper, , Belgium

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Site BE32013

Liège, , Belgium

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Site BG35923

Pazardzhik, , Bulgaria

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Site BG35906

Sofia, , Bulgaria

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Site BG35908

Sofia, , Bulgaria

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Site BG35910

Sofia, , Bulgaria

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Site BG35907

Stara Zagora, , Bulgaria

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Site BG35916

Varna, , Bulgaria

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Site BG35903

Veliko Tarnovo, , Bulgaria

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Site CO57007

Barranquilla, , Colombia

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Site CO57008

Barranquilla, , Colombia

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Site CO57002

Pereira, , Colombia

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Site DO17101

La Fe Santo Domingo, , Dominican Republic

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Site DO17102

Santiago de los Caballeros, , Dominican Republic

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Site DO17104

Santo Domingo, , Dominican Republic

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Site DO17103

Santo Domingo, , Dominican Republic

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Site EE37201

Tallinn, , Estonia

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Site GE99503

Tbilisi, , Georgia

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Site GE99504

Tbilisi, , Georgia

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Site GE99502

Tbilisi, , Georgia

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Site GR30003

Heraklion, , Greece

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Site GR30002

Pátrai, , Greece

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Site GR30001

Thessaloniki, , Greece

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Site GT50209

Chiquimula, , Guatemala

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Site GT50205

Guatemala City, , Guatemala

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Site GT50206

Guatemala City, , Guatemala

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Site GT50203

Guatemala City, , Guatemala

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Site GT50202

Guatemala City, , Guatemala

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Site GT50208

Guatemala City, , Guatemala

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Site GT50207

Guatemala City, , Guatemala

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Site GT50201

Guatemala City, , Guatemala

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Site HU36029

Budapest, , Hungary

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Site HU36025

Győr, , Hungary

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Site HU36026

Kaposvár, , Hungary

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Site HU36027

Kistarcsa, , Hungary

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Site HU36008

Pécs, , Hungary

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Site HU36028

Szent, , Hungary

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Site HU36003

Zalsaegerszeg, , Hungary

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Site IT39001

Bari, , Italy

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Site IT39008

Lecco, , Italy

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Site IT39006

Milan, , Italy

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Site IT39037

Modena, , Italy

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Site IT39036

Pavia, , Italy

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Site PA50703

Colón, , Panama

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Site PA50701

Panama City, , Panama

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Site PE51001

Iquitos, , Peru

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Site PE51002

Trujillo, , Peru

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Site PL48001

Krakow, Malopolska, Poland

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Site PL48002

Katowice, , Poland

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Site PL48012

Lodz, , Poland

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Site PL48008

Lodz, , Poland

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Site PL48057

Nowy Tomyśl, , Poland

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Site PL48013

Szczecin, , Poland

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Site PL48007

Tarnów, , Poland

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Site PL48005

Warsaw, , Poland

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Site PL48004

Warsaw, , Poland

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Site PL48006

Wroclaw, , Poland

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Site PL48014

Zamość, , Poland

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Site RO40005

Timișoara, Timiș County, Romania

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Site RO40001

Brasov, , Romania

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Site RO40021

Bucharest, , Romania

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Site RO40012

Bucharest, , Romania

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Site RO40003

Bucharest, , Romania

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Site RO40004

Oradea, , Romania

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Site RU70024

Chelyabinsk, , Russia

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Site RU70054

Irkutsk, , Russia

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Site RU70008

Kaluga, , Russia

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Site RU70051

Moscow, , Russia

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Site RU70007

Moscow, , Russia

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Site RU70005

Moscow, , Russia

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Site RU70048

Moscow, , Russia

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Site RU70047

Moscow, , Russia

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Site RU70003

Nizhny Novgorod, , Russia

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Site RU70004

Omsk, , Russia

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Site RU70043

Petrozavodsk, , Russia

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Site RU70014

Rostov-on-Don, , Russia

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Site RU70022

Saint Petersburg, , Russia

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Site RU70045

Saint Petersburg, , Russia

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Site RU70011

Saint Petersburg, , Russia

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Site RU70002

Saint Petersburg, , Russia

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Site RU70060

Saratov, , Russia

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Site RU70006

Smolensk, , Russia

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Site RU70057

Yaroslavl, , Russia

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Site RU70001

Yaroslavl, , Russia

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Site RS38102

Belgrade, , Serbia

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Site RS38104

Belgrade, , Serbia

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Site RS38105

Belgrade, , Serbia

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Site RS38103

Belgrade, , Serbia

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Site RS38117

Kruševac, , Serbia

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Site RS38101

Niš, , Serbia

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Site RS38116

Zrenjanin, , Serbia

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Site ZA27001

Observatory, Cape Town, South Africa

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Site ZA27004

Bloemfontein, Free State, South Africa

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Site ZA27002

Durban, KwaZulu-Natal, South Africa

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Site ZA27008

Durban, , South Africa

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Site ZA27006

Parow, , South Africa

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Site ZA27007

Port Elizabeth, , South Africa

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Site ES34010

Alcorcón, Madrid, Spain

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Site ES34011

Galdakao, Vizcaya, Spain

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Site ES34002

Badalona-Barcelona, , Spain

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Site ES34003

Barcelona, , Spain

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Site ES34006

Barcelona, , Spain

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Site ES34007

Ciudad Real, , Spain

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Site TR90003

Ankara, , Turkey (Türkiye)

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Site TR90016

Edirne, , Turkey (Türkiye)

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Site TR90024

Kocaeli, , Turkey (Türkiye)

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Site TR90020

Malatya, , Turkey (Türkiye)

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Site UA38009

Lviv, Lvivska, Ukraine

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Site UA38021

Cherkasy, , Ukraine

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Site UA38003

Chernivtsi, , Ukraine

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Site UA38006

Dnipro, , Ukraine

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Site UA38016

Ivano-Frankivsk, , Ukraine

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Site UA38011

Kharkiv, , Ukraine

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Site UA38015

Kherson, , Ukraine

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Site UA38010

Kyiv, , Ukraine

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Site UA38012

Kyiv, , Ukraine

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Site UA38017

Kyiv, , Ukraine

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Site UA38007

Mykolaiv, , Ukraine

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Site UA38008

Odesa, , Ukraine

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Site UA38019

Odesa, , Ukraine

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Site UA38001

Ternopil, , Ukraine

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Site UA38018

Uzhhorod, , Ukraine

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Site UA38002

Zaporizhzhya, , Ukraine

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Site GB44008

Cambridge, , United Kingdom

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Site GB44001

Swansea, , United Kingdom

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Site GB44005

Welwyn Garden City, , United Kingdom

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Site GB44004

Westcliff-on-Sea, , United Kingdom

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Countries

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Belarus Belgium Bulgaria Colombia Dominican Republic Estonia Georgia Greece Guatemala Hungary Italy Panama Peru Poland Romania Russia Serbia South Africa Spain Turkey (Türkiye) Ukraine United Kingdom

References

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Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.

Reference Type DERIVED
PMID: 36005278 (View on PubMed)

Provenzano R, Szczech L, Leong R, Saikali KG, Zhong M, Lee TT, Little DJ, Houser MT, Frison L, Houghton J, Neff TB. Efficacy and Cardiovascular Safety of Roxadustat for Treatment of Anemia in Patients with Non-Dialysis-Dependent CKD: Pooled Results of Three Randomized Clinical Trials. Clin J Am Soc Nephrol. 2021 Aug;16(8):1190-1200. doi: 10.2215/CJN.16191020.

Reference Type DERIVED
PMID: 34362786 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://astellasclinicalstudyresults.com/study.aspx?ID=363

Link to results on Astellas Clinical Study Results website

Other Identifiers

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2012-005180-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1517-CL-0608

Identifier Type: -

Identifier Source: org_study_id

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