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NCT06677060PHASE3Recruiting

Phase III Study Investigating Heart Failure and Cardiovascular Death With Baxdrostat in Combination With Dapagliflozin

AstraZeneca

Start Date

3/14/2025

Completion Date

12/17/2029

Summary

Participants include men and women ≥ 40 years of age with T2DM, established CV disease, a history of HTN with an SBP of at least 130 mmHg at screening, who meet the predefined serum potassium level, and with at least one additional risk factor for HF. The study will include an optional pre-screening period to facilitate sites' identification of potentially eligible participants to enter the full screening assessments. Participants will not be required to visit the site and no informed consent is required for the optional pre-screening period. The pre-screening assessments do not replace the full screening tests at Visit 1. Upon entering the screening period, all consented participants (after signature of screening ICF) will be screened during an up to 14-day screening period. Participants who meet all screening inclusion/exclusion criteria but are not treated with SGLT2i or are treated for less than 4 weeks will enter a run-in period with dapagliflozin 10 mg once daily for at least 4 weeks (and not more than 6 weeks) before randomisation. Site visits will take place at approximately 2-, 4-, 8-, 16-, and 34-weeks following randomisation. Thereafter visits will occur approximately every 4 months. The study closure procedures will be initiated when the predetermined number of the first secondary endpoint events (ie, the composite of hospitalisation for HF or CV death) is predicted to have occurred i.e., the PACD. In case of premature discontinuation of the blinded study intervention, participants will remain in the study. Unless a participant meets the dapagliflozin specific discontinuation criteria, they will continue to receive open label dapagliflozin 10 mg. It is important that the scheduled study visits and data collection continue according to the study protocol.

Eligibility Criteria

Age Range: 40 years to No maximum

Inclusion Criteria: * Participants of any sex and gender must be ≥ 40 years old at the time of signing the informed consent. * Diagnosed with T2DM and requiring treatment * Established CV disease (ischaemic heart disease, cerebrovascular disease, peripheral arterial disease) * History of HTN and an SBP ≥ 130 mmHg at screening and ≥ 120 mmHg at the Randomisation Visit. * At least one additional risk factor for HF: * Age ≥ 70 years * UACR \> 20 mg/g * eGFR \< 60 mL/min/1.73 m2 * History of polyvascular disease (at least two of: ischaemic heart disease, cerebrovascular disease, and peripheral arterial disease) * History of atrial fibrillation or atrial flutter * NT-proBNP \> 125 ng/L Exclusion Criteria: * Previously confirmed diagnosis and treatment of heart failure * An eGFR \< 30 mL/min/1.73 m2 at screening * Known hyperkalaemia, defined as potassium ≥ 5.5 mmol/L within 3 months prior to screening * Type 1 diabetes mellitus or uncontrolled T2DM with HbA1c \> 10.5% (\> 91 mmol/mol) at screening * Serum sodium \< 135 mmol/L at screening, determined as per central laboratory assessment * Stroke, transient ischaemic cerebral attack, valve implantation or valve replacement, carotid surgery, carotid angioplasty, or cardiac surgery, within 3 months prior to randomisation * Myocardial infarction within 3 months prior to randomisation, or within 1 month prior to randomisation when there is no further planned revascularisation * Percutaneous coronary intervention within 1 month prior to randomisation * Known severe hepatic impairment, defined as Child-Pugh Class C, based on records that confirm documented medical history * Documented history of adrenal insufficiency * Any dialysis (including for acute kidney injury) within 3 months prior to screening * Any acute kidney injury within 3 months prior to screening * Prohibited concomitant medications

Interventions

DRUG

Baxdrostat and dapagliflozin

OTHER

Placebo and dapagliflozin

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Conditions

Heart Failure

Locations

Research Site

Birmingham, Alabama 35205

United States

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Centreville, Alabama 35042

United States

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Fairhope, Alabama 36532

United States

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Huntsville, Alabama 35801

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Mobile, Alabama 36608

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Sheffield, Alabama 35660

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Vestavia Hills, Alabama 35216

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Anchorage, Alaska 99508

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Gilbert, Arizona 85296

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Glendale, Arizona 85308

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Tempe, Arizona 85283

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Tucson, Arizona 85712

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Dublin, California 94568

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Huntington Beach, California 92648

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Inglewood, California 90301

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La Jolla, California 92037

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Lakewood, California 90805

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Lincoln, California 95648

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Loma Linda, California 92357

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Los Angeles, California 90035

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Los Angeles, California 90073

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Sacramento, California 95841

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San Diego, California 92120

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San Dimas, California 91773

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San Francisco, California 94115

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San Francisco, California 94121

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Santa Maria, California 93454

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Sherman Oaks, California 91403

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Thousand Oaks, California 91360

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Aurora, Colorado 80012

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Englewood, Colorado 80110

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Bridgeport, Connecticut 06606

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Stamford, Connecticut 06905

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Waterbury, Connecticut 06708

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Crystal River, Florida 34429

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Fort Lauderdale, Florida 33316

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Fort Myers, Florida 33912

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Gainesville, Florida 32608

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Jacksonville, Florida 32216

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Lakeland, Florida 33813

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Miami, Florida 33125

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Miami, Florida 33135

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Miami, Florida 33173

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Miami, Florida 33175

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Miami Lakes, Florida 33016

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Ocoee, Florida 34761

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Orlando, Florida 32822

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Palmetto Bay, Florida 33157

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Saint Augustine, Florida 32086

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Albany, Georgia 31707

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Atlanta, Georgia 30303

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Canton, Georgia 30114

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Columbus, Georgia 31904

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Cordele, Georgia 31015

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Suwanee, Georgia 30024

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Tucker, Georgia 30084

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Woodstock, Georgia 30189

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Idaho Falls, Idaho 83404

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Champaign, Illinois 61822

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Chicago, Illinois 60616

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Chicago, Illinois 60621

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Chicago, Illinois 60631

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Gurnee, Illinois 60031

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Island Lake, Illinois 60042

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Park Ridge, Illinois 60068

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Indianapolis, Indiana 46202

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Munster, Indiana 46321

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Richmond, Indiana 47374

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South Bend, Indiana 46617

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El Dorado, Kansas 67042

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Lenexa, Kansas 66219

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Newton, Kansas 67114

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Wichita, Kansas 67218

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Lexington, Kentucky 40509

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Louisville, Kentucky 40218

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Owensboro, Kentucky 42301

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Paducah, Kentucky 42001

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Alexandria, Louisiana 71303

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Bossier City, Louisiana 71111

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Shreveport, Louisiana 71101

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Baltimore, Maryland 21229

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Beltsville, Maryland 20705

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Lutherville-Timonium, Maryland 21093

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Potomac, Maryland 20854

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Boston, Massachusetts 02115

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New Bedford, Massachusetts 02740

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Roslindale, Massachusetts 02131

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Farmington Hills, Michigan 48336

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Flint, Michigan 48532

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Troy, Michigan 48098

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Ypsilanti, Michigan 48197

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Mankato, Minnesota 56001

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Minneapolis, Minnesota 55417

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Columbia, Missouri 65201

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Kansas City, Missouri 64111

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Kansas City, Missouri 64151

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St Louis, Missouri 63136

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Kalispell, Montana 59901

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Missoula, Montana 59804

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Norfolk, Nebraska 68701

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Omaha, Nebraska 68134

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Carson City, Nevada 89706

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Portsmouth, New Hampshire 03801

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Eatontown, New Jersey 07724

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Pennington, New Jersey 08534

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Somerset, New Jersey 08873

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Albuquerque, New Mexico 87102

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Albuquerque, New Mexico 87108

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Albany, New York 12208

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Albany, New York 12211

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Brooklyn, New York 11201

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Brooklyn, New York 11220

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Massapequa, New York 11758

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New York, New York 10029

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Queens Village, New York 11428

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Charlotte, North Carolina 28287

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Durham, North Carolina 27701

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Fayetteville, North Carolina 28304

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Kernersville, North Carolina 27284

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Kinston, North Carolina 28504

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Monroe, North Carolina 28112

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New Bern, North Carolina 28562

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New Bern, North Carolina 28562

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Raleigh, North Carolina 27607

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Rocky Mount, North Carolina 27804

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Wilmington, North Carolina 28401

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Fargo, North Dakota 58104

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Beavercreek, Ohio 45431

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Canton, Ohio 44718

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Cincinnati, Ohio 45219

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Cincinnati, Ohio 45220

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Columbus, Ohio 43215

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Columbus, Ohio 43228

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Dayton, Ohio 45424

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Maumee, Ohio 43537

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Toledo, Ohio 43606

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Norman, Oklahoma 73069

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Oklahoma City, Oklahoma 73111

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Oklahoma City, Oklahoma 73120

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Medford, Oregon 97504

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Camp Hill, Pennsylvania 17011

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Horsham, Pennsylvania 19044

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Philadelphia, Pennsylvania 19114

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Scottdale, Pennsylvania 15683

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Smithfield, Pennsylvania 15478

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West Chester, Pennsylvania 19380

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Columbia, South Carolina 29209

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Fort Mill, South Carolina 29715

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Greenville, South Carolina 29615

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Mt. Pleasant, South Carolina 29464

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North Charleston, South Carolina 29405

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Spartanburg, South Carolina 29301

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Cleveland, Tennessee 37312

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Morristown, Tennessee 37813

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Nashville, Tennessee 37203

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Abilene, Texas 79606

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Austin, Texas 78704

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Beaumont, Texas 77702

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Brownsville, Texas 78526

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Dallas, Texas 75390-9015

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Duncanville, Texas 75137

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El Paso, Texas 79905

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El Paso, Texas 79935

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Houston, Texas 77084

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Houston, Texas 77089

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Lewisville, Texas 75067

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Mansfield, Texas 76063

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McAllen, Texas 78501

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McAllen, Texas 78503

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Mesquite, Texas 75149

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Paris, Texas 75462

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Pearland, Texas 77584

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San Antonio, Texas 78231

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San Antonio, Texas 78257

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Stephenville, Texas 76401

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Sugar Land, Texas 77479

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Tomball, Texas 77375

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Weslaco, Texas 78596

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Woodway, Texas 76712

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Clearfield, Utah 84015

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Ogden, Utah 84405

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Burlington, Vermont 05401

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Burke, Virginia 22015

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Charlottesville, Virginia 22911

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Fairfax, Virginia 22033

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Falls Church, Virginia 22042

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Manassas, Virginia 20110

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Midlothian, Virginia 23112

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Norfolk, Virginia 23502

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Norfolk, Virginia 23504

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Richmond, Virginia 23249

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Salem, Virginia 24153

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Puyallup, Washington 98372

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Redmond, Washington 98052

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Renton, Washington 98057

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Kingwood, West Virginia 26537

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Morgantown, West Virginia 26505

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Green Bay, Wisconsin 54303

United States

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Milwaukee, Wisconsin 53226

United States

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Buenos Aires, C1425AGC

Argentina

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CABA, C1056ABH

Argentina

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CABA, C1119ACN

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CABA, C1120AAC

Argentina

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Caba, C1128AAF

Argentina

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Ciudad de Buenos Aires, C1428DCO

Argentina

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Córdoba, 5000

Argentina

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Córdoba, X5003DCP

Argentina

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La Plata, B1904

Argentina

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Mar del Plata, B7600FZN

Argentina

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Mar del Plata, B7600GNY

Argentina

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Rosario, 2000

Argentina

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Rosario, S2000PBJ

Argentina

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San Nicolás, B2900DMH

Argentina

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San Nicolás de los Arroyos, B2900DPA

Argentina

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San Vicente, 5006

Argentina

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Santa Fe, S3000FWO

Argentina

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Adelaide, 5000

Australia

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Castle Hill, 2154

Australia

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Coffs Harbour, 02450

Australia

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Elizabeth Vale, 5112

Australia

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Fremantle, 6160

Australia

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Geelong, 3220

Australia

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Kingswood, 2747

Australia

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Leabrook, 5068

Australia

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Maroubra, 2035

Australia

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Merewether, 2291

Australia

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Milton, 4064

Australia

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Mulgrave, 3170

Australia

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Osborne Park, 6017

Australia

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Rockhampton, 4700

Australia

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Wollongong, 2500

Australia

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Belém, 66073-005

Brazil

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Blumenau, 89010-022

Brazil

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Bragança Paulista, 12916-542

Brazil

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Brasília, 71625-009

Brazil

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Campina Grande do Sul, 83.430-000

Brazil

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Campinas, 13060-080

Brazil

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Campinas, 13060-904

Brazil

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Curitiba, 80030-480

Brazil

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Curitiba, 80810-050

Brazil

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Juiz de Fora, 36033-318

Brazil

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Natal, 59020-035

Brazil

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Porto Alegre, 90160-093

Brazil

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Porto Alegre, 9061-000

Brazil

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Porto Alegre, 90630-165

Brazil

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Porto Alegre, 91350-200

Brazil

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Rio de Janeiro, 20241-180

Brazil

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São José do Rio Preto, 15090-000

Brazil

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São José dos Campos, 12230-001

Brazil

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São Paulo, 01228-000

Brazil

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São Paulo, 01236-030

Brazil

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São Paulo, 04012-180

Brazil

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São Paulo, 05403-000

Brazil

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Tatuí, 18270-170

Brazil

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Haskovo, 6300

Bulgaria

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Panagyurishte, 4500

Bulgaria

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Petrich, 2850

Bulgaria

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Pleven, 5800

Bulgaria

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Pleven, 5804

Bulgaria

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Plovdiv, 4003

Bulgaria

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Rousse, 7000

Bulgaria

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Shumen, 9700

Bulgaria

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Sofia, 1000

Bulgaria

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Sofia, 1309

Bulgaria

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Sofia, 1404

Bulgaria

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Sofia, 1431

Bulgaria

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Sofia, 1527

Bulgaria

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Sofia, 1618

Bulgaria

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Sofia, 1680

Bulgaria

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Stara Zagora, 6003

Bulgaria

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Varna, 9000

Bulgaria

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Calgary, Alberta T2H 2G4

Canada

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Calgary, Alberta T2V 4J2

Canada

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Sherwood Park, Alberta T8H 0N2

Canada

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Abbotsford British Columbia, British Columbia V2S 0C2

Canada

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Moncton, New Brunswick E1C 2Z3

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Saint John, New Brunswick E2L 4L2

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St. John's, Newfoundland and Labrador A1B 3V6

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Halifax, Nova Scotia B3H 1V7

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Sydney, Nova Scotia B1P 1P3

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Cambridge, Ontario N1R 6V6

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Guelph, Ontario N1H 1B1

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Hamilton, Ontario L8J 0B6

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Hamilton, Ontario L8L 5G4

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Markham, Ontario L3S 0A2

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Newmarket, Ontario L3Y 2P6

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North York, Ontario M6B 3H7

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North York, Ontario M9N 1W4

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Oakville, Ontario L6K 3W7

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Ottawa, Ontario K2J 0V2

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Sarnia, Ontario N7T 4X3

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Scarborough Village, Ontario M1B 4Z8

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Toronto, Ontario M4G 3E8

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Toronto, Ontario M5B 1W8

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Toronto, Ontario M6G 1M2

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Toronto, Ontario M6G 3S5

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Laval, Quebec H7T 2P5

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Lévis, Quebec G6V 9H4

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Mirabel, Quebec J7J 2K8

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Montreal, Quebec H1T 1C8

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Montreal, Quebec H4A 3T2

Canada

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Québec, Quebec G1G 5X1

Canada

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Québec, Quebec G1V 4G5

Canada

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Saint-Charles-Borromée, Quebec J6E 6J2

Canada

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Sherbrooke, Quebec J1H 5N4

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Terrebonne, Quebec J6X 4P7

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Trois-Rivières, Quebec G9A 4P3

Canada

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Regina, Saskatchewan S4P 0W5

Canada

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Baotou, 14010

China

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Beijing, 100029

China

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Beijing, 100029

China

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Beijing, 100050

China

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Changchun, 130021

China

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Changchun, 130033

China

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Changde, 415000

China

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Changsha, 410011

China

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Changsha, 410015

China

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Changzhou, 272100

China

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Chengdu, 610000

China

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Chengdu, 610041

China

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Chifeng, 024000

China

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Chongqing, 400014

China

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Chongqing, 400042

China

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Guangzhou, 510100

China

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Guangzhou, 511486

China

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Harbin, 150000

China

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Hefei, 230001

China

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Hengyang, 421001

China

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Heze, 274099

China

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Huangshi, 435000

China

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Huizhou, 516002

China

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Jinan, 250001

China

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Jining, 272006

China

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Kaifeng, 475000

China

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Liaocheng, 252000

China

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Linyi, 276003

China

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Lishui, 323000

China

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Luoyang, 471000

China

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Luoyang, 471001

China

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Meihekou, 135022

China

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Nanchang, 330009

China

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Nanjing, 210008

China

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Nantong, 226001

China

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Nanyang, 473000

China

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Panjin, 124009

China

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Pingxiang, 337055

China

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Sanya, 572000

China

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Shanghai, 200240

China

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Shanghai, 201114

China

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Shenyang, 110016

China

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Siping, 136000

China

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Suzhou, 215004

China

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Taiyuan, 030024

China

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Taizhou, 317000

China

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Tianjin, 300000

China

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Wenzhou, 325000

China

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Wuhan, 430010

China

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Wuhan, 430060

China

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Xi'an, 710061

China

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Xi'an, 710068

China

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Xianyang, 750004

China

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Xuzhou, 221009

China

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Yinchuan, 750004

China

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Zhumadian, 463000

China

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Zigong, 643000

China

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Benešov, 256 01

Czechia

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Brandýs nad Labem, 250 01

Czechia

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Brno, 603 00

Czechia

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Brno, 639 00

Czechia

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Broumov, 55001

Czechia

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Chlumec nad Cidlinou, 503 51

Czechia

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Hodonín, 695 01

Czechia

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Humpolec, 396 01

Czechia

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Jílové u Prahy, 254 01

Czechia

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Krnov, 794 01

Czechia

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Olomouc, 772 00

Czechia

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Ostrava, 702 00

Czechia

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Pilsen, 301 00

Czechia

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Police nad Metují, 549 54

Czechia

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Prague, 101 00

Czechia

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Prague, 104 00

Czechia

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Prague, 12808

Czechia

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Prague, 149 00

Czechia

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Prague, 150 00

Czechia

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Prague, 190 14

Czechia

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Aarhus, 8200

Denmark

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Aarhus N, 8200

Denmark

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Copenhagen, 2300

Denmark

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Esbjerg, 6700

Denmark

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Frederiksberg, 2000

Denmark

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Gistrup, 9260

Denmark

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Herlev, 2730

Denmark

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Herning, 7400

Denmark

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Hillerød, 3400

Denmark

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Hjørring, 9800

Denmark

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Holbæk, 4300

Denmark

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Hvidovre, 2650

Denmark

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Roskilde, 4000

Denmark

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Slagelse, DK-4200

Denmark

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Svendborg, 5700

Denmark

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Viborg, 8800

Denmark

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Amiens, 80054

France

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Angers, 49933

France

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Aurillac, 15002

France

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Besançon, 25030

France

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Bobigny, 93000

France

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Bois-Guillaume, 76230

France

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Brest, 29200

France

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Caen, 14033

France

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Cholet, 49300

France

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Clermont-Ferrand, 63000

France

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Colombes, 92700

France

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Corbeil-Essonnes, 91106

France

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Dijon, 2100

France

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La Roche-sur-Yon, 85925

France

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La Rochelle, 17000

France

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Le Coudray, 28630

France

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Le Creusot, 71206

France

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Lyon, 69007

France

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Marseille, 13385

France

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Montpellier, 34295

France

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Nantes, 44093

France

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Narbonne, 11108

France

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Nîmes, 30029

France

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Paris, 75010

France

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Paris, 75014

France

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Paris, 75018

France

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Paris, 75908

France

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Pierre-Bénite, 69495

France

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Toulouse, 31059

France

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Vandœuvre-lès-Nancy, 54511

France

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Villeurbanne, 69100

France

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Aachen, 52074

Germany

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Amberg, 92224

Germany

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Bad Homburg, 61348

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Brandenburg an der Havel, 14770

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Germany

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Germany

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Leipzig, 04249

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Ludwigshafen, 67059

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Germany

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Markkleeberg, 04416

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Germany

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Balatonfüred, 8230

Hungary

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Ahmedabad, 380054

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India

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Israel

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Amagasaki-shi, 660-8550

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Malaysia

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Acapulco, 39670

Mexico

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Bellavista, CALLAO 2

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Angeles City, 2009

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Odunpazari, 26080

Turkey (Türkiye)

Research Site

Samsun, 55270

Turkey (Türkiye)

Research Site

Sivas, 58140

Turkey (Türkiye)

Research Site

Chernivtsі, 58002

Ukraine

Research Site

Ivano-Frankivsk, 76018

Ukraine

Research Site

Kyiv, 01601

Ukraine

Research Site

Kyiv, 02081

Ukraine

Research Site

Kyiv, 03037

Ukraine

Research Site

Kyiv, 03151

Ukraine

Research Site

Kyiv, 03680

Ukraine

Research Site

Kyiv, 04050

Ukraine

Research Site

Ternopil, 46000

Ukraine

Research Site

Ternopil, 46002

Ukraine

Research Site

Uzhhorod, 88014

Ukraine

Research Site

Vinnytsia, 21001

Ukraine

Research Site

Vinnytsia, 21029

Ukraine

Research Site

Zhytomyr, 100002

Ukraine

Research Site

Aberdeen, AB25 2ZN

United Kingdom

Research Site

Chesterfield, S40 4AA

United Kingdom

Research Site

Dundee, DD1 9SY

United Kingdom

Research Site

Gatley, SK8 4NQ

United Kingdom

Research Site

Glasgow, G31 2ER

United Kingdom

Research Site

Glasgow, G51 4TF

United Kingdom

Research Site

London, E11BB

United Kingdom

Research Site

Norwich, NR128DU

United Kingdom

Research Site

Penzance, TR18 3DX

United Kingdom

Research Site

Redruth, TR16 4ET

United Kingdom

Research Site

Sandbach, CW11 1EQ

United Kingdom

Research Site

Southampton, SO303JB

United Kingdom

Research Site

Stockton-on-Tees, TS19 8PE

United Kingdom

Research Site

Swansea, SA6 6NL

United Kingdom

Research Site

Weston-super-Mare, BS24 7PR

United Kingdom

Research Site

Wolverhampton, WV10 0QP

United Kingdom

Research Site

Woodbridge, IP136TH

United Kingdom

Research Site

Yate, BS37 4AX

United Kingdom

Research Site

Can Tho, 900000

Vietnam

Research Site

Haiphong, 180000

Vietnam

Research Site

Hanoi, 10000

Vietnam

Research Site

Hà Nội, 100000

Vietnam

Research Site

Ho Chi Minh City, 700000

Vietnam

Research Site

Ho Chi Minh City, 700000

Vietnam

Research Site

Ho Chi Minh City, 70000

Vietnam

Research Site

Hochiminh City, 700000

Vietnam

Research Site

Huế, 530000

Vietnam

Research Site

Rach Gia, 920000

Vietnam

Research Site

Vĩnh Yên, 280000

Vietnam