NCT02174627

Brief Summary

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

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
2,781

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jun 2014

Typical duration for phase_3

Geographic Reach
26 countries

359 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 24, 2014

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 25, 2014

Completed
1 day until next milestone

Study Start

First participant enrolled

June 26, 2014

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 4, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 4, 2018

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

December 16, 2019

Completed
Last Updated

December 16, 2019

Status Verified

November 1, 2019

Enrollment Period

4.3 years

First QC Date

June 24, 2014

Results QC Date

October 4, 2019

Last Update Submit

November 27, 2019

Conditions

Keywords

Renal,CKD,Roxadustat,anemia,non-dialysis

Outcome Measures

Primary Outcomes (1)

  • Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52

    Baseline Hb was defined as the mean of the last 3 central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to mean value from Week 28 to Week 52 was analyzed using a missing at random (MAR) based multiple imputation analysis of covariance (ANCOVA) model with baseline Hb, baseline estimated glomerular filtration rate (eGFR), cardiovascular (CV) history, geographic region and treatment group as fixed effect covariates. The adjusted least squares (LS) mean estimates of change from baseline to mean during Week 28 to Week 52 are presented.

    Baseline (Day 1, Week 0) and Week 28 to Week 52.

Secondary Outcomes (10)

  • Percentage of Participants With Hb Response During the First 24 Weeks of Treatment

    Baseline (Day 1, Week 0) up to Week 24.

  • Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52 in Participants With Baseline High Sensitivity C-Reactive Protein (hsCRP) Greater Than the Upper Limit of Normal (ULN)

    Baseline (Day 1, Week 0) and Week 28 to Week 52.

  • Proportion of Total Time of Interpolated Hb Values Greater Than or Equal To 10 g/dL From Week 28 to Week 52

    Week 28 up to Week 52.

  • Proportion of Total Time of Interpolated Hb Values Within the Interval of 10 to 12 g/dL From Week 28 to Week 52

    Week 28 up to Week 52.

  • Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24

    Baseline (Day 1, Week 0) and Week 24

  • +5 more secondary outcomes

Study Arms (2)

Roxadustat

EXPERIMENTAL
Drug: Roxadustat

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

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.

Roxadustat

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

Placebo

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Provision of informed consent prior to any study specific procedures.
  • Age ≥18 years at screening visit 1
  • 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
  • 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
  • Ferritin ≥50 ng/mL at randomization (obtained from screening visit)
  • TSAT ≥15 % at randomization (obtained from screening visit)
  • Serum folate level ≥ lower limit of normal (LLN) at randomization (obtained from screening visit)
  • Serum vitamin B12 level ≥LLN at randomization (obtained from screening visit)
  • 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)
  • Body weight 45 to 160 kg

You may not qualify if:

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
  • Previous randomization in the present study
  • Any erythropoietin analogue treatment within 6 weeks of randomization
  • New York Heart Association Class III or IV congestive heart failure at enrollment
  • 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
  • History of chronic liver disease (e.g., chronic infectious hepatitis, chronic auto- immune liver disease, cirrhosis or fibrosis of the liver)
  • 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
  • Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis)
  • 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
  • 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
  • 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
  • Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibody (anti-HCV Ab)
  • 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
  • Known hemosiderosis, hemochromatosis or hypercoagulable condition
  • Any prior organ transplant or a scheduled organ transplantation date
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (359)

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Birmingham, Alabama, 35209, United States

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Huntsville, Alabama, 35805, United States

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Phoenix, Arizona, 85027, United States

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Bakersfield, California, 93309, United States

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El Centro, California, 92243, United States

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Escondido, California, 92025, United States

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Glendale, California, 91204, United States

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Long Beach, California, 90806, United States

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Long Beach, California, 90807, United States

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Los Angeles, California, 90022, United States

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Los Angeles, California, 90095, United States

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Lynwood, California, 90262, United States

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National City, California, 91950, United States

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Northridge, California, 91324, United States

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Orange, California, 92868, United States

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Sacramento, California, 95825, United States

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Sacramento, California, 95831, United States

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San Diego, California, 92103, United States

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San Dimas, California, 91773, United States

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San Francisco, California, 94110, United States

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San Luis Obispo, California, 93401, United States

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Upland, California, 91786, United States

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Arvada, Colorado, 80002, United States

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Waterbury, Connecticut, 06708, United States

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Aventura, Florida, 33180, United States

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Coral Gables, Florida, 33134, United States

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Coral Springs, Florida, 33071, United States

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Edgewater, Florida, 32132, United States

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Hollywood, Florida, 33021, United States

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Kissimmee, Florida, 34741, United States

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Lauderdale Lakes, Florida, 33313, United States

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Miami, Florida, 33126, United States

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Miami, Florida, 33130, United States

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Miami, Florida, 33133, United States

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Miami, Florida, 33145, United States

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Miami, Florida, 33150, United States

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Miami, Florida, 33165, United States

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Miami, Florida, 33169, United States

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Miami, Florida, 33173, United States

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Port Charlotte, Florida, 33952, United States

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Tampa, Florida, 33607, United States

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Atlanta, Georgia, 30342, United States

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Columbus, Georgia, 31901, United States

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Columbus, Georgia, 31904, United States

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Joliet, Illinois, 60435, United States

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La Grange, Illinois, 60525, United States

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Metairie, Louisiana, 70006, United States

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Shreveport, Louisiana, 71101, United States

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Rockport, Maine, 04856, United States

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Greenbelt, Maryland, 20770, United States

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Rockville, Maryland, 20852, United States

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Port Huron, Michigan, 48060, United States

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Gulfport, Mississippi, 39501, United States

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Kansas City, Missouri, 64111, United States

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Omaha, Nebraska, 68124, United States

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Las Vegas, Nevada, 89106, United States

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Las Vegas, Nevada, 89128, United States

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Reno, Nevada, 89511, United States

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Rochester, New Hampshire, 03867, United States

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Flushing, New York, 11355, United States

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Great Neck, New York, 11021, United States

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Charlotte, North Carolina, 28207, United States

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High Point, North Carolina, 27262, United States

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Jacksonville, North Carolina, 28546, United States

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New Bern, North Carolina, 28562, United States

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Wilmington, North Carolina, 28401, United States

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Cincinnati, Ohio, 45206, United States

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Cincinnati, Ohio, 45220, United States

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Columbus, Ohio, 43215, United States

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Oklahoma City, Oklahoma, 73116, United States

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Bethlehem, Pennsylvania, 18017, United States

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Lansdale, Pennsylvania, 19446, United States

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Philadelphia, Pennsylvania, 19104, United States

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Uniontown, Pennsylvania, 15401, United States

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Providence, Rhode Island, 02908, United States

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Providence, Rhode Island, 02915, United States

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Columbia, South Carolina, 29203, United States

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Knoxville, Tennessee, 37923, United States

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Corpus Christi, Texas, 78404, United States

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Cypress, Texas, 77429, United States

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Dallas, Texas, 75231, United States

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Houston, Texas, 77004, United States

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Houston, Texas, 77024, United States

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Houston, Texas, 77074, United States

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Houston, Texas, 77084, United States

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Houston, Texas, 77090, United States

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Houston, Texas, 77099, United States

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Lufkin, Texas, 75904, United States

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San Antonio, Texas, 78207, United States

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San Antonio, Texas, 78212, United States

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San Antonio, Texas, 78229, United States

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San Antonio, Texas, 78258, United States

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Salt Lake City, Utah, 84115, United States

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St. George, Utah, 84790, United States

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Norfolk, Virginia, 23507, United States

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Salem, Virginia, 24153, United States

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Woodbridge, Virginia, 22191, United States

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CABA, C1012AAR, Argentina

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CABA, C1440AAD, Argentina

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Capital Federal, C1425AGC, Argentina

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Ciudad Autónoma de Bs. As., C1199ABB, Argentina

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Ciudadela, 1702, Argentina

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La Plata, 1900, Argentina

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La Plata, C1427ARO, Argentina

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Lanús, B1824KAJ, Argentina

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Mar del Plata, 7600, Argentina

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Munro, 1605, Argentina

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Ramos Mejía, B1704ETD, Argentina

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Rosario, 2000, Argentina

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Rosario, S2000DNM, Argentina

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San Isidro, B1642DCD, Argentina

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San Miguel de Tucumán, 4000, Argentina

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Santa Rosa, 6300, Argentina

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Curitiba, 80230-130, Brazil

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Curitiba, 80440-020, Brazil

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Curitiba, 80810-040, Brazil

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Feira de Santana, 44001-584, Brazil

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Fortaleza, 60115282, Brazil

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Fortaleza, 60430-350, Brazil

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Fortaleza, 60430-370, Brazil

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Goiânia, 74043-011, Brazil

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Joinville, Brazil

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Juiz de Fora, 36036-330, Brazil

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Maringá, 87083-240, Brazil

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Porto Alegre, 90035-003, Brazil

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Porto Alegre, 90160-093, Brazil

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Porto Alegre, 90610-000, Brazil

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São Bernardo do Campo, 09715090, Brazil

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São Paulo, 01323-030, Brazil

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São Paulo, 04039-000, Brazil

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São Paulo, 05403-000, Brazil

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São Paulo, 08270-070, Brazil

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Botevgrad, 2140, Bulgaria

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Dupnitsa, 2600, Bulgaria

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Gotse Delchev, 2900, Bulgaria

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Haskovo, 6300, Bulgaria

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Kozloduy, 3320, Bulgaria

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Samokov, 2000, Bulgaria

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Sandanski, 2800, Bulgaria

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Silistra, 7500, Bulgaria

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Sliven, 8800, Bulgaria

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Smolyan, 3700, Bulgaria

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Yambol, 8600, Bulgaria

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Edmonton, Alberta, T6G 2B7, Canada

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Kamloops, British Columbia, V2C 2T1, Canada

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New Westminster, British Columbia, V3L 0A6, Canada

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Winnipeg, Manitoba, R2V 3M3, Canada

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Saint John, New Brunswick, E2L 4L2, Canada

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Sydney, Nova Scotia, B1P 1P3, Canada

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Brampton, Ontario, L6R 3J7, Canada

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Brampton, Ontario, L6T 0G1, Canada

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Kitchener, Ontario, N2H 5Z8, Canada

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London, Ontario, N6A 5A5, Canada

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Oakville, Ontario, L6K 3V3, Canada

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Scarborough Village, Ontario, M1H 3G4, Canada

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Toronto, Ontario, M4C 5T2, Canada

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Toronto, Ontario, M4S 1Y2, Canada

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Toronto, Ontario, M5C 2T2, Canada

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Toronto, Ontario, M9N 1N8, Canada

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Whitby, Ontario, L1N 5T2, Canada

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Gatineau, Quebec, J8Y 6S8, Canada

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Greenfield Park, Quebec, J4V 2H1, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Montreal, Quebec, H4J 1C5, Canada

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Québec, Quebec, G1R 2J6, Canada

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Cali, 760032, Colombia

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Chía, 250008, Colombia

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Medellín, 5001000, Colombia

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Zipaquirá, 250258, Colombia

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Brno, 625 00, Czechia

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Havlíčkův Brod, 580 22, Czechia

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Ivančice, 664 91, Czechia

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Prague, 190 61, Czechia

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Rychnov nad Kněžnou, 516 01, Czechia

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Slaný, 274 01, Czechia

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Slavkov u Brna, Czechia

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Šumperk, 787 01, Czechia

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Ústí nad Labem, 401 13, Czechia

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Ústí nad Orlicí, 562 18, Czechia

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Berlin, 10117, Germany

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Cloppenburg, 49661, Germany

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Cologne, 50937, Germany

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Ajka, 8400, Hungary

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Budapest, 1096, Hungary

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Budapest, 1134, Hungary

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Gyula, 5700, Hungary

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Hatvan, 3000, Hungary

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Kecskemét, 6000, Hungary

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Nyíregyháza, 4400, Hungary

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Pécs, 7623, Hungary

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Polgár, 4090, Hungary

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Salgótarján, 3100, Hungary

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Siófok, 8600, Hungary

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Tatabánya, 2800, Hungary

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Velence, 2481, Hungary

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Ahmedabad, 380016, India

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Bangalore, 560052, India

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Bangalore, 560068, India

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Bangalore, 560070, India

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Chennai, 600006, India

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Ghaziabad NCR, 201012, India

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Hyderabad, 500018, India

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Hyderabad, 500072, India

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Kolkata, 700027, India

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Lucknow, 226003, India

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Maharashtra, 411013, India

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Mumbai, 400008, India

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Mysore, 570004, India

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Nagpur, 420012, India

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Nagpur, 440003, India

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Nagpur, 440012, India

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New Delhi, 110017, India

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New Delhi, 110060, India

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Pune, 411001, India

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Vijayawada, 520 008, India

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Vijayawada, 522002, India

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Visakhapatnam, 530002, India

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George Town, 10990, Malaysia

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Kubang Kerian, 16150, Malaysia

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Putrajaya, 62250, Malaysia

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Taiping, 34000, Malaysia

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Aguascalientes, 20219, Mexico

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Culiacán, 80230, Mexico

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Guadalajara, 44670, Mexico

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Guadalajara, 44676, Mexico

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México, 06726, Mexico

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Minatitlán, 96730, Mexico

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Veracruz, 91900, Mexico

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Xalapa, 91020, Mexico

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Bellavista, CALLAO 2, Peru

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Ica, Peru

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Lima, 14, Peru

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Lima, L17, Peru

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Lima, LIMA 01, Peru

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Lima, LIMA 1, Peru

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Lima, LIMA 27, Peru

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Lima, LIMA 31, Peru

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Trujillo, 044, Peru

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Cebu City, 6000, Philippines

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Iloilo City, 5000, Philippines

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Quezon City, 1101, Philippines

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Ciechanów, 06-400, Poland

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Gmina Końskie, 26-200, Poland

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Lodz, 90-141, Poland

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Poznan, 60-355, Poland

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Sochaczew, 96-500, Poland

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Tczew, 83-110, Poland

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Cidra, 00739, Puerto Rico

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Rio Piedras, 00935, Puerto Rico

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Río Grande, 00745, Puerto Rico

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San Juan, 00909, Puerto Rico

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San Juan, 00917, Puerto Rico

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San Juan, 00921, Puerto Rico

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San Juan, 00927, Puerto Rico

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Toa Baja, 00949, Puerto Rico

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Arad, 310017, Romania

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Bucharest, 010731, Romania

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Bucharest, 020475, Romania

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Târgu Mureş, 540000, Romania

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Timișoara, 300736, Romania

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Arkhangelsk, 163001, Russia

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Barnaul, 656024, Russia

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Irkutsk, 664049, Russia

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Izhevsk, 426035, Russia

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Kemerovo, 650066, Russia

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Krasnoyarsk, 660062, Russia

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Moscow, 105229, Russia

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Moscow, 109263, Russia

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Moscow, 129344, Russia

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Nizhny Novgorod, 603076, Russia

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Nizhny Novgorod, 603126, Russia

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Perm, 614000, Russia

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Ryazan, 390027, Russia

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Saint Petersburg, 191015, Russia

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Saint Petersburg, 194354, Russia

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Saint Petersburg, 196601, Russia

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Ufa, 450000, Russia

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Ufa, 450005, Russia

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Ufa, 450071, Russia

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Volgograd, 404120, Russia

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Bratislava, 82606, Slovakia

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Bratislava, 831 03, Slovakia

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Košice, 04011, Slovakia

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Kráľovský Chlmec, 077 01, Slovakia

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Nové Zámky, 940 34, Slovakia

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Zvolen, 960 01, Slovakia

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Ansan-si, 15355, South Korea

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Busan, 49241, South Korea

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Daegu, 42415, South Korea

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Daejeon, 35015, South Korea

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Goyang-si, 10380, South Korea

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Goyang-si, 10444, South Korea

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Incheon, 403-720, South Korea

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Seongnam-si, 13620, South Korea

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Seoul, 03312, South Korea

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Seoul, 06273, South Korea

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Seoul, 08308, South Korea

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Seoul, 139-711, South Korea

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Uijeongbu-si, 11765, South Korea

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Almería, 04009, Spain

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Málaga, 29010, Spain

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Santiago de Compostela, 15706, Spain

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Seville, 41013, Spain

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Valencia, 46010, Spain

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Valencia, 46017, Spain

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Valencia, 46026, Spain

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Kaohsiung City, 82445, Taiwan

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Keelung, 20401, Taiwan

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New Taipei City, 220, Taiwan

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New Taipei City, 231, Taiwan

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New Taipei City, 23561, Taiwan

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Taichung, 402, Taiwan

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Taipei, 0116, Taiwan

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Taipei, 10491, Taiwan

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Taipei, Taiwan

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Taoyuan District, 333, Taiwan

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Bangkok, 10300, Thailand

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Khon Kaen, 40000, Thailand

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Khon Kaen, 40002, Thailand

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Adana, 01330, Turkey (Türkiye)

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Ankara, 06230, Turkey (Türkiye)

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Ankara, 06490, Turkey (Türkiye)

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Antalya, Turkey (Türkiye)

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Istanbul, 34093, Turkey (Türkiye)

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Istanbul, 34098, Turkey (Türkiye)

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Izmir, 35040, Turkey (Türkiye)

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Chernivtsi, 58002, Ukraine

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Dnipro, 49005, Ukraine

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Ivano-Frankivsk, 76008, Ukraine

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Kharkiv, 61002, Ukraine

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Kharkiv, 61039, Ukraine

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Kharkiv, 61058, Ukraine

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Kharkiv, 61103, Ukraine

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Khmelnytsky, 29000, Ukraine

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Kirovograd, 25006, Ukraine

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Kyiv, 01601, Ukraine

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Kyiv, 02125, Ukraine

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Kyiv, 04050, Ukraine

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Kyiv, 04114, Ukraine

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Lutsk, 43005, Ukraine

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Lviv, 79010, Ukraine

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Odesa, 65009, Ukraine

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Rivne, 33027, Ukraine

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Vinnytsia, 21018, Ukraine

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Zaporizhzhya, 69001, Ukraine

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Zaporizhzhya, 69068, Ukraine

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Zaporizhzhya, 69118, Ukraine

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Can Tho, 900000, Vietnam

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Hanoi, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Hochiminh, 550000, Vietnam

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Hochiminh, 700000, Vietnam

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Huế, 530000, Vietnam

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Related Publications (3)

  • 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.

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Anemia

Interventions

roxadustat

Condition Hierarchy (Ancestors)

Hematologic DiseasesHemic and Lymphatic Diseases

Limitations and Caveats

20 participants were excluded from the analysis due to Good Clinical Practice violations or system technical issues (9 in roxadustat group and 11 in placebo group). Higher IP discontinuation was observed in placebo group versus in roxadustat group.

Results Point of Contact

Title
Global Clinical Lead
Organization
AstraZeneca

Study Officials

  • Steven Fishbane, MD

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

    PRINCIPAL INVESTIGATOR
  • Mark Houser, MD

    AZ R&D Gaithersburg, USA

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 24, 2014

First Posted

June 25, 2014

Study Start

June 26, 2014

Primary Completion

October 4, 2018

Study Completion

October 4, 2018

Last Updated

December 16, 2019

Results First Posted

December 16, 2019

Record last verified: 2019-11

Locations