Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Dialysis-dependent Chronic Kidney Disease (DD-CKD)

NCT ID: NCT02892149

Last Updated: 2022-06-28

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

3554 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-08-31

Study Completion Date

2020-03-30

Brief Summary

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A multicenter, randomized, open-label, active-controlled Phase 3 study for the maintenance treatment of anemia in participants with dialysis-dependent chronic kidney disease (DD-CKD)

Detailed Description

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This is a multicenter, randomized, open-label, active-controlled Phase 3 study of the efficacy and safety of Vadadustat versus Darbepoetin alfa for the maintenance treatment of anemia in participants with DD-CKD

Conditions

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Anemia Dialysis-Dependent Chronic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Sponsor was blinded during the study

Study Groups

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Vadadustat

Group Type EXPERIMENTAL

Vadadustat

Intervention Type DRUG

Oral dose administered once daily for ≥36 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.

Darbepoetin alfa

Group Type ACTIVE_COMPARATOR

Darbepoetin alfa

Intervention Type DRUG

Subcutaneous or intravenous dose administered for ≥36 weeks. Initial dose based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.

Interventions

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Vadadustat

Oral dose administered once daily for ≥36 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.

Intervention Type DRUG

Darbepoetin alfa

Subcutaneous or intravenous dose administered for ≥36 weeks. Initial dose based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.

Intervention Type DRUG

Other Intervention Names

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AKB-6548 Aranesp

Eligibility Criteria

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Inclusion Criteria

* ≥18 years of age
* Receiving chronic maintenance dialysis (either peritoneal or hemodialysis) for end-stage kidney disease for at least 12 weeks prior to Screening
* Currently maintained on erythropoiesis-stimulating agent therapy, with a dose received within 6 weeks prior to or during Screening
* Mean Screening hemoglobin between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive) in the US and between 9.0 and 12.0 g/dL (inclusive) outside of the US
* Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening

Exclusion Criteria

* Anemia due to a cause other than chronic kidney disease or participants with active bleeding or recent blood loss
* Uncontrolled hypertension
* Red blood cell transfusion within 8 weeks prior to randomization
* Anticipated to recover adequate kidney function to no longer require dialysis
* Severe heart failure at Screening (New York Heart Association Class IV)
* Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure, or stroke within 12 weeks prior to or during Screening
* Hypersensitivity to Vadadustat, Darbepoetin alfa, or any of their excipients
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Akebia Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chief Medical Officer

Role: STUDY_DIRECTOR

Akebia Therapeutics Inc.

Locations

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Huntsville, Alabama, United States

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Mesa, Arizona, United States

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Pine Bluff, Arkansas, United States

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Anaheim, California, United States

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Bakersfield, California, United States

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Bakersfield, California, United States

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Canyon Country, California, United States

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Chula Vista, California, United States

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Downey, California, United States

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El Centro, California, United States

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Escondido, California, United States

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Fairfield, California, United States

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Glendale, California, United States

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Granada Hills, California, United States

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Granada Hills, California, United States

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La Habra, California, United States

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La Mesa, California, United States

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Lakewood, California, United States

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Long Beach, California, United States

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Long Beach, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Montebello, California, United States

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Monterey Park, California, United States

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Newhall, California, United States

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Northridge, California, United States

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Northridge, California, United States

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Riverside, California, United States

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Riverside, California, United States

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Roseville, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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San Diego, California, United States

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San Dimas, California, United States

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San Dimas, California, United States

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Simi Valley, California, United States

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Tarzana, California, United States

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Whittier, California, United States

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Whittier, California, United States

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Arvada, Colorado, United States

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Denver, Colorado, United States

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Westminster, Colorado, United States

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Stamford, Connecticut, United States

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Bradenton, Florida, United States

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Coral Gables, Florida, United States

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Coral Springs, Florida, United States

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Coral Springs, Florida, United States

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Hollywood, Florida, United States

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Lauderdale Lakes, Florida, United States

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Miami, Florida, United States

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AMPM Research Clinic

Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami Beach, Florida, United States

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Ocala, Florida, United States

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Pembroke Pines, Florida, United States

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Tampa, Florida, United States

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Winter Park, Florida, United States

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Augusta, Georgia, United States

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Columbus, Georgia, United States

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Columbus, Georgia, United States

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Lawrenceville, Georgia, United States

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Lawrenceville, Georgia, United States

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Roswell, Georgia, United States

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Statesboro, Georgia, United States

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Meridian, Idaho, United States

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Fort Wayne, Indiana, United States

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Merrillville, Indiana, United States

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Monroe, Louisiana, United States

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Shreveport, Louisiana, United States

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Takoma Park, Maryland, United States

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Springfield, Massachusetts, United States

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Detroit, Michigan, United States

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Pontiac, Michigan, United States

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Port Huron, Michigan, United States

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Roseville, Michigan, United States

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Columbus, Mississippi, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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Albuquerque, New Mexico, United States

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Gallup, New Mexico, United States

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Santa Fe, New Mexico, United States

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Astoria, New York, United States

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Flushing, New York, United States

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Great Neck, New York, United States

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New York, New York, United States

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New York, New York, United States

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The Bronx, New York, United States

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Yonkers, New York, United States

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Asheville, North Carolina, United States

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Charlotte, North Carolina, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Greenville, North Carolina, United States

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New Bern, North Carolina, United States

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New Bern, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Philadelphia, Pennsylvania, United States

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Providence, Rhode Island, United States

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Chattanooga, Tennessee, United States

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Chattanooga, Tennessee, United States

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Knoxville, Tennessee, United States

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Nashville, Tennessee, United States

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Arlington, Texas, United States

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Austin, Texas, United States

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Austin, Texas, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Duncanville, Texas, United States

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El Paso, Texas, United States

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Greenville, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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McAllen, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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St. George, Utah, United States

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South Burlington, Vermont, United States

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Hampton, Virginia, United States

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Manassas, Virginia, United States

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Norfolk, Virginia, United States

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Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina

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Junín, Buenos Aires, Argentina

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Pergamino, Buenos Aires, Argentina

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Sarandí, Buenos Aires, Argentina

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Corrientes, , Argentina

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Córdoba, , Argentina

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Córdoba, , Argentina

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Salta, , Argentina

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San Luis, , Argentina

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Liverpool, New South Wales, Australia

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New Lambton Heights, New South Wales, Australia

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Wahroonga, New South Wales, Australia

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Cairns, Queensland, Australia

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Launceston, Tasmania, Australia

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Box Hill, Victoria, Australia

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Fitzroy, Victoria, Australia

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Nedlands, Western Australia, Australia

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Fortaleza, Ceará, Brazil

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Vitória, Espírito Santo, Brazil

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Feira de Santana, Estado de Bahia, Brazil

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Itabuna, Estado de Bahia, Brazil

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Belo Horizonte, Minas Gerais, Brazil

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Belo Horizonte, Minas Gerais, Brazil

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Juiz de Fora, Minas Gerais, Brazil

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Juiz de Fora, Minas Gerais, Brazil

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Curitiba, Paraná, Brazil

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Maringá, Paraná, Brazil

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Canoas, Rio Grande do Sul, Brazil

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Passo Fundo, Rio Grande do Sul, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Criciúma, Santa Catarina, Brazil

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Joinville, Santa Catarina, Brazil

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Santo André, São Paulo, Brazil

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Santo André, São Paulo, Brazil

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São Bernardo do Campo, São Paulo, Brazil

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São José do Rio Preto, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Byala, , Bulgaria

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Cherven Bryag, , Bulgaria

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Dobrich, , Bulgaria

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Dupnitsa, , Bulgaria

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Haskovo, , Bulgaria

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Plovdiv, , Bulgaria

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Rousse, , Bulgaria

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Shumen, , Bulgaria

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Silistra, , Bulgaria

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Sliven, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Veliko Tarnovo, , Bulgaria

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Vidin, , Bulgaria

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Vratsa, , Bulgaria

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Halifax, Nova Scotia, Canada

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Sydney, Nova Scotia, Canada

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Greater Sudbury, Ontario, Canada

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Oshawa, Ontario, Canada

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Marseille, Bouches-du-Rhône, France

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Bordeaux, Gironde, France

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Reims, Marne, France

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Saint-Priest-En-Jarez, Pays de la Loire Region, France

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Paris, , France

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Paris, , France

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Villingen-Schwenningen, Baden-Wurttemberg, Germany

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Rostock, Mecklenburg-Vorpommern, Germany

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Düsseldorf, North Rhine-Westphalia, Germany

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Berlin, , Germany

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Ashkelon, , Israel

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Haifa, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Rishon LeZiyyon, , Israel

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Bari, , Italy

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Genova, , Italy

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Lecco, , Italy

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Pavia, , Italy

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Roma, , Italy

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Siena, , Italy

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Pachuca, Hidalgo, Mexico

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Zapopan, Jalisco, Mexico

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Morelia, Michoacán, Mexico

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Culiacán, Sinaloa, Mexico

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Biała Podlaska, , Poland

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Golub-Dobrzyń, , Poland

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Kołobrzeg, , Poland

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Lodz, , Poland

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Lodz, , Poland

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Lodz, , Poland

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Warsaw, , Poland

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Beja, , Portugal

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Leiria, , Portugal

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Loures, , Portugal

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Kemerovo, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Nizhny Novgorod, , Russia

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Novorossiysk, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Yekaterinburg, , Russia

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Belgrade, , Serbia

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Belgrade, , Serbia

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Belgrade, , Serbia

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Belgrade, , Serbia

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Kragujevac, , Serbia

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Niš, , Serbia

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Zaječar, , Serbia

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Chuncheon, Gangwon-do, South Korea

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Bucheon-si, Gyeonggi-do, South Korea

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Goyang-si, Gyeonggi-do, South Korea

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Goyang-si, Gyeonggi-do, South Korea

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Guri-si, Gyeonggi-do, South Korea

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Seongnam-si, Gyeonggi-do, South Korea

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Suwon, Gyeonggi-do, South Korea

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Busan, , South Korea

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Busan, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Brovary, , Ukraine

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Cherkassy, , Ukraine

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Dnipro, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kharkiv, , Ukraine

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Kyiv, , Ukraine

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Mykolaiv, , Ukraine

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Ternopil, , Ukraine

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Uzhhorod, , Ukraine

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Vinnytsia, , Ukraine

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Zaporizhzhia, , Ukraine

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Zhytomyr, , Ukraine

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Cambridge, Cambridgeshire, United Kingdom

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London, Greater London, United Kingdom

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Stevenage, Hertfordshire, United Kingdom

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Kettering, Leicestershire, United Kingdom

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Doncaster, South Yorkshire, United Kingdom

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Countries

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United States Argentina Australia Brazil Bulgaria Canada France Germany Israel Italy Mexico Poland Portugal Russia Serbia South Korea Ukraine United Kingdom

References

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Chertow GM, Eckardt KU, Sarnak MJ, Winkelmayer WC, Agarwal R, Minga T, Luo W, Burke SK. Safety and Efficacy of Vadadustat for the Treatment of CKD-Related Anemia within and outside the United States. J Am Soc Nephrol. 2025 Oct 1;36(10):1984-1997. doi: 10.1681/ASN.0000000708. Epub 2025 May 13. No abstract available.

Reference Type DERIVED
PMID: 40359056 (View on PubMed)

Sarnak MJ, Agarwal R, Boudville N, Chowdhury PCP, Eckardt KU, Gonzalez CR, Kooienga LA, Koury MJ, Ntoso KA, Luo W, Parfrey PS, Vargo DL, Winkelmayer WC, Zhang Z, Chertow GM. Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis. Nephrol Dial Transplant. 2023 Sep 29;38(10):2358-2367. doi: 10.1093/ndt/gfad074.

Reference Type DERIVED
PMID: 37096396 (View on PubMed)

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)

Eckardt KU, Agarwal R, Aswad A, Awad A, Block GA, Bacci MR, Farag YMK, Fishbane S, Hubert H, Jardine A, Khawaja Z, Koury MJ, Maroni BJ, Matsushita K, McCullough PA, Lewis EF, Luo W, Parfrey PS, Pergola P, Sarnak MJ, Spinowitz B, Tumlin J, Vargo DL, Walters KA, Winkelmayer WC, Wittes J, Zwiech R, Chertow GM. Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021 Apr 29;384(17):1601-1612. doi: 10.1056/NEJMoa2025956.

Reference Type DERIVED
PMID: 33913638 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-001360-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AKB-6548-CI-0017

Identifier Type: -

Identifier Source: org_study_id

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