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

NCT ID: NCT02174627

Last Updated: 2019-12-16

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

2781 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-26

Study Completion Date

2018-10-04

Brief Summary

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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

Detailed Description

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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.

Conditions

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Anemia

Keywords

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Renal, CKD, Roxadustat, anemia, non-dialysis

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

Group Type EXPERIMENTAL

Roxadustat

Intervention Type DRUG

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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FibroGen

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Steven Fishbane, MD

Role: PRINCIPAL_INVESTIGATOR

Chief Division of Kidney Diseases and Hypertension, North Shore University Hospital, Great Neck, NY, USA

Mark Houser, MD

Role: STUDY_DIRECTOR

AZ R&D Gaithersburg, USA

Locations

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Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Phoenix, Arizona, United States

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Bakersfield, California, United States

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El Centro, California, United States

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Escondido, California, United States

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Glendale, 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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Los Angeles, California, United States

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Lynwood, California, United States

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National City, California, United States

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Northridge, California, United States

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Orange, California, United States

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Sacramento, 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 Dimas, California, United States

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San Francisco, California, United States

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San Luis Obispo, California, United States

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Upland, California, United States

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Arvada, Colorado, United States

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Waterbury, Connecticut, United States

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Aventura, 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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Edgewater, Florida, United States

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Hollywood, Florida, United States

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Kissimmee, Florida, United States

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Lauderdale Lakes, Florida, United States

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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, Florida, United States

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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, Florida, United States

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Port Charlotte, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Columbus, Georgia, United States

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Columbus, Georgia, United States

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Joliet, Illinois, United States

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La Grange, Illinois, United States

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Metairie, Louisiana, United States

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Shreveport, Louisiana, United States

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Rockport, Maine, United States

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Greenbelt, Maryland, United States

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Rockville, Maryland, United States

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Port Huron, Michigan, United States

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Gulfport, Mississippi, United States

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Kansas City, Missouri, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Las Vegas, Nevada, United States

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Reno, Nevada, United States

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Rochester, New Hampshire, 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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Charlotte, North Carolina, United States

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High Point, North Carolina, United States

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Jacksonville, North Carolina, United States

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New Bern, North Carolina, United States

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Wilmington, North Carolina, United States

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Cincinnati, Ohio, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Bethlehem, Pennsylvania, United States

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Lansdale, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Uniontown, Pennsylvania, United States

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Providence, Rhode Island, United States

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Providence, Rhode Island, United States

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Columbia, South Carolina, United States

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Knoxville, Tennessee, United States

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Corpus Christi, Texas, United States

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Cypress, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Lufkin, 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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Salt Lake City, Utah, United States

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St. George, Utah, United States

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Norfolk, Virginia, United States

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Salem, Virginia, United States

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Woodbridge, Virginia, United States

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CABA, , Argentina

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CABA, , Argentina

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Capital Federal, , Argentina

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Ciudad Autónoma de Bs. As., , Argentina

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Ciudadela, , Argentina

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La Plata, , Argentina

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La Plata, , Argentina

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Lanús, , Argentina

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Mar del Plata, , Argentina

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Munro, , Argentina

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Ramos Mejía, , Argentina

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Rosario, , Argentina

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Rosario, , Argentina

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San Isidro, , Argentina

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San Miguel de Tucumán, , Argentina

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Santa Rosa, , Argentina

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Curitiba, , Brazil

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Curitiba, , Brazil

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Curitiba, , Brazil

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Feira de Santana, , Brazil

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Fortaleza, , Brazil

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Fortaleza, , Brazil

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Fortaleza, , Brazil

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Goiânia, , Brazil

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Joinville, , Brazil

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Juiz de Fora, , Brazil

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Maringá, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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São Bernardo do Campo, , Brazil

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São Paulo, , Brazil

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Botevgrad, , Bulgaria

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Dupnitsa, , Bulgaria

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Gotse Delchev, , Bulgaria

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Haskovo, , Bulgaria

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Kozloduy, , Bulgaria

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Samokov, , Bulgaria

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Sandanski, , Bulgaria

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Silistra, , Bulgaria

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Sliven, , Bulgaria

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Smolyan, , Bulgaria

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Yambol, , Bulgaria

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Edmonton, Alberta, Canada

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Kamloops, British Columbia, Canada

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New Westminster, British Columbia, Canada

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Winnipeg, Manitoba, Canada

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Saint John, New Brunswick, Canada

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Sydney, Nova Scotia, Canada

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Brampton, Ontario, Canada

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Brampton, Ontario, Canada

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Kitchener, Ontario, Canada

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London, Ontario, Canada

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Oakville, Ontario, Canada

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Scarborough Village, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Whitby, Ontario, Canada

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Gatineau, Quebec, Canada

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Cali, , Colombia

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Chía, , Colombia

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Medellín, , Colombia

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Zipaquirá, , Colombia

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Brno, , Czechia

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Havlíčkův Brod, , Czechia

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Ivančice, , Czechia

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Prague, , Czechia

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Rychnov nad Kněžnou, , Czechia

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Slaný, , Czechia

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Slavkov u Brna, , Czechia

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Šumperk, , Czechia

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Ústí nad Labem, , Czechia

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Ústí nad Orlicí, , Czechia

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Berlin, , Germany

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Cloppenburg, , Germany

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Cologne, , Germany

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Ajka, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Gyula, , Hungary

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Hatvan, , Hungary

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Kecskemét, , Hungary

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Nyíregyháza, , Hungary

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Pécs, , Hungary

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Polgár, , Hungary

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Salgótarján, , Hungary

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Siófok, , Hungary

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Tatabánya, , Hungary

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Velence, , Hungary

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Ahmedabad, , India

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Bangalore, , India

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Bangalore, , India

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Bangalore, , India

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Chennai, , India

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Ghaziabad NCR, , India

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Hyderabad, , India

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Hyderabad, , India

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Kolkata, , India

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Lucknow, , India

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Maharashtra, , India

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Mumbai, , India

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Mysore, , India

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Nagpur, , India

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Nagpur, , India

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Nagpur, , India

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New Delhi, , India

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New Delhi, , India

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Pune, , India

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Vijayawada, , India

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Vijayawada, , India

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Visakhapatnam, , India

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George Town, , Malaysia

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Kubang Kerian, , Malaysia

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Putrajaya, , Malaysia

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Taiping, , Malaysia

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Aguascalientes, , Mexico

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Culiacán, , Mexico

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Guadalajara, , Mexico

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Guadalajara, , Mexico

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México, , Mexico

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Minatitlán, , Mexico

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Veracruz, , Mexico

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Xalapa, , Mexico

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Bellavista, , Peru

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Ica, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Trujillo, , Peru

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Cebu City, , Philippines

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Iloilo City, , Philippines

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Quezon City, , Philippines

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Ciechanów, , Poland

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Gmina Końskie, , Poland

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Lodz, , Poland

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Poznan, , Poland

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Sochaczew, , Poland

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Tczew, , Poland

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Cidra, , Puerto Rico

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Rio Piedras, , Puerto Rico

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Río Grande, , Puerto Rico

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San Juan, , Puerto Rico

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San Juan, , Puerto Rico

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San Juan, , Puerto Rico

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San Juan, , Puerto Rico

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Toa Baja, , Puerto Rico

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Arad, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Târgu Mureş, , Romania

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Timișoara, , Romania

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Arkhangelsk, , Russia

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Barnaul, , Russia

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Irkutsk, , Russia

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Izhevsk, , Russia

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Kemerovo, , Russia

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Krasnoyarsk, , Russia

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Moscow, , 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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Perm, , Russia

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Ryazan, , 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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Ufa, , Russia

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Ufa, , Russia

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Ufa, , Russia

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Volgograd, , Russia

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Bratislava, , Slovakia

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Bratislava, , Slovakia

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Košice, , Slovakia

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Kráľovský Chlmec, , Slovakia

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Nové Zámky, , Slovakia

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Zvolen, , Slovakia

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Ansan-si, , South Korea

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Busan, , South Korea

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Daegu, , South Korea

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Daejeon, , South Korea

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Goyang-si, , South Korea

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Goyang-si, , South Korea

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Incheon, , South Korea

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Seongnam-si, , 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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Uijeongbu-si, , South Korea

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Almería, , Spain

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Málaga, , Spain

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Santiago de Compostela, , Spain

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Seville, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Kaohsiung City, , Taiwan

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Keelung, , Taiwan

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New Taipei City, , Taiwan

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New Taipei City, , Taiwan

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New Taipei City, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Khon Kaen, , Thailand

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Khon Kaen, , Thailand

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Antalya, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Chernivtsi, , Ukraine

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Dnipro, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kharkiv, , Ukraine

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Kharkiv, , Ukraine

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Kharkiv, , Ukraine

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Kharkiv, , Ukraine

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Khmelnytsky, , Ukraine

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Kirovograd, , Ukraine

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Kyiv, , Ukraine

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Kyiv, , Ukraine

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Kyiv, , Ukraine

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Kyiv, , Ukraine

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Kyiv, , Ukraine

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Lutsk, , Ukraine

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Lviv, , Ukraine

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Odesa, , Ukraine

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Rivne, , Ukraine

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Vinnytsia, , Ukraine

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Vinnytsia, , Ukraine

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Zaporizhzhya, , Ukraine

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Zaporizhzhya, , Ukraine

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Zaporizhzhya, , Ukraine

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Zaporizhzhya, , Ukraine

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Can Tho, , Vietnam

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Hanoi, , Vietnam

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Ho Chi Minh City, , Vietnam

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Hochiminh, , Vietnam

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Hochiminh, , Vietnam

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Huế, , Vietnam

Site Status

Countries

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Italy United Kingdom United States Argentina Brazil Bulgaria Canada Colombia Czechia Germany Hungary India Malaysia Mexico Peru Philippines Poland Puerto Rico Romania Russia Slovakia South Korea Spain Taiwan Thailand Turkey (Türkiye) Ukraine Vietnam

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)

Fishbane S, El-Shahawy MA, Pecoits-Filho R, Van BP, Houser MT, Frison L, Little DJ, Guzman NJ, Pergola PE. Roxadustat for Treating Anemia in Patients with CKD Not on Dialysis: Results from a Randomized Phase 3 Study. J Am Soc Nephrol. 2021 Mar;32(3):737-755. doi: 10.1681/ASN.2020081150. Epub 2021 Feb 10.

Reference Type DERIVED
PMID: 33568383 (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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D5740C00001

Identifier Type: -

Identifier Source: org_study_id