MedPath

Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol

Phase 3
Completed
Conditions
ASCVD
Elevated Cholesterol
Interventions
Registration Number
NCT03399370
Lead Sponsor
The Medicines Company
Brief Summary

This is a Phase III, placebo-controlled, double-blind, randomized study in participants with ASCVD and elevated LDL-C despite maximum tolerated dose of LDL-C lowering therapies to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) inclisiran injection(s). The study will be a multicenter study in the United States.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1561
Inclusion Criteria
  1. Male or female participants ≥18 years of age.
  2. History of ASCVD (coronary heart disease [CHD], cardiovascular disease [CVD], or peripheral arterial disease [PAD]).
  3. Serum LDL-C ≥1.8 millimole (mmol)/liter (L) (≥70 mg/dL).
  4. Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.
  5. Participants on statins should be receiving a maximally tolerated dose.
  6. Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins.
  7. Subjects on lipid-lower therapies (such as a statin and/or ezetimibe) should be on a stable dose for ≥30 days before screening with no planned medication or dose change during study participation.
Exclusion Criteria
  1. New York Heart Association (NYHA) class IV heart failure.

  2. Uncontrolled cardiac arrhythmia

  3. Uncontrolled severe hypertension

  4. Active liver disease

  5. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 methods of highly effective contraception (failure rate less than 1% per year) (for example, combined oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, or intrauterine device) for the entire duration of the study. Exemptions from this criterion:

    1. Women >2 years postmenopausal (defined as 1 year or longer since last menstrual period) and more than 55 years of age.
    2. Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of randomization.
    3. Women who are surgically sterilized at least 3 months prior to enrollment.
  6. Males who are unwilling to use an acceptable method of birth control during the entire study period (such as condom with spermicide).

  7. Treatment with other investigational products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer.

  8. Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Saline SolutionPlaceboPlacebo will be administered as a SC injection of saline solution on Day 1, Day 90, then every 6 months.
InclisiranInclisiran SodiumInclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90, then every 6 months.
Primary Outcome Measures
NameTimeMethod
Percentage Change in LDL-C From Baseline to Day 510Baseline, Day 510
Time-adjusted Percentage Change in LDL-C Levels From Baseline After Day 90 and up to Day 540Baseline, Day 90 to Day 540

Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported

Secondary Outcome Measures
NameTimeMethod
Absolute Change in LDL-C From Baseline to Day 510Baseline, Day 510
Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540Baseline, Day 90 to Day 540

Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported

Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510Baseline, Day 510
Percentage Change in Total Cholesterol From Baseline to Day 510Baseline, Day 510
Percentage Change in Apolipoprotein B (ApoB) From Baseline to Day 510Baseline, Day 510
Percentage Change in Non-HDL-C From Baseline to Day 510Baseline, Day 510

Trial Locations

Locations (145)

Research Site 10001-069

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Atlanta, Georgia, United States

Research Site 10001-158

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Chicago, Illinois, United States

Research Site 10001-035

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Chicago, Illinois, United States

Research Site 10001-014

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Columbus, Ohio, United States

Research Site 10001-012

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Columbus, Ohio, United States

Research Site 10001-031

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Houston, Texas, United States

Research Site 10001-091

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Houston, Texas, United States

Research Site 10001-061

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Houston, Texas, United States

Research Site 10001-112

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Las Vegas, Nevada, United States

Research Site 10001-124

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Las Vegas, Nevada, United States

Research Site 10001-081

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Miami, Florida, United States

Research Site 10001-140

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Miami, Florida, United States

Research Site 10001-082

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Indianapolis, Indiana, United States

Research Site 10001-142

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Miami, Florida, United States

Research Site 10001-089

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Miami, Florida, United States

Research Site 10001-120

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Cincinnati, Ohio, United States

Research Site 10001-154

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Cincinnati, Ohio, United States

Research Site 10001-010

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Cincinnati, Ohio, United States

Research Site 10001-134

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Cincinnati, Ohio, United States

Research Site 10001-071

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San Antonio, Texas, United States

Research Site 10001-002

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Salt Lake City, Utah, United States

Research Site 10001-052

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Salt Lake City, Utah, United States

Research Site 10001-028

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Hutchinson, Kansas, United States

Research Site 10001-113

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Huntsville, Alabama, United States

Research Site 10001-132

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Tucson, Arizona, United States

Research Site 10001-155

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Clearwater, Florida, United States

Research Site 10001-099

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Clearwater, Florida, United States

Research Site 10001-127

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Daytona Beach, Florida, United States

Research Site 10001-011

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Carlsbad, California, United States

Research Site 10001-084

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Clearwater, Florida, United States

Research Site 10001-043

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Northridge, California, United States

Research Site 10001-070

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Fort Lauderdale, Florida, United States

Research Site 10001-019

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Tucson, Arizona, United States

Research Site 10001-022

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Northridge, California, United States

Research Site 10001-008

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Santa Rosa, California, United States

Research Site 10001-119

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Fleming Island, Florida, United States

Research Site 10001-048

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Pembroke Pines, Florida, United States

Research Site 10001-123

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Sarasota, Florida, United States

Research Site 10001-067

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Hialeah, Florida, United States

Research Site 10001-102

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Saint Petersburg, Florida, United States

Research Site 10001-153

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Spring Valley, California, United States

Research Site 10001-080

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Miami Springs, Florida, United States

Research Site 10001-039

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Jacksonville, Florida, United States

Research Site 10001-098

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Jacksonville, Florida, United States

Research Site 10001-027

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Pembroke Pines, Florida, United States

Research Site 10001-003

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Pinellas Park, Florida, United States

Research Site 10001-030

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Miami, Florida, United States

Research Site 10001-104

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Ponte Vedra, Florida, United States

Research Site 10001-053

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Omaha, Nebraska, United States

Research Site 10001-021

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Omaha, Nebraska, United States

Research Site 10001-015

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Birmingham, Alabama, United States

Research Site 10001-037

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Montgomery, Alabama, United States

Research Site 10001-138

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Foley, Alabama, United States

Research Site 10001-013

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Chandler, Arizona, United States

Research Site 10001-076

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Saraland, Alabama, United States

Research Site 10001-058

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Mobile, Alabama, United States

Research Site 10001-136

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Phoenix, Arizona, United States

Research Site 10001-051

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Surprise, Arizona, United States

Research Site 10001-004

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Tucson, Arizona, United States

Research Site 10001-050

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Canoga Park, California, United States

Research Site 10001-073

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Beverly Hills, California, United States

Research Site 10001-150

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Los Angeles, California, United States

Research Site 10001-105

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San Ramon, California, United States

Research Site 10001-044

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Torrance, California, United States

Research Site 10001-047

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Boca Raton, Florida, United States

Research Site 10001-139

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Jacksonville, Florida, United States

Research Site 10001-116

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Miami, Florida, United States

Research Site 10001-115

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Pembroke Pines, Florida, United States

Research Site 10001-147

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Pembroke Pines, Florida, United States

Research Site 10001-090

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Saint Augustine, Florida, United States

Research Site 10001-092

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Macon, Georgia, United States

Research Site 10001-059

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Arlington Heights, Illinois, United States

Research Site 10001-036

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Evanston, Illinois, United States

Research Site 1001-020

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Sellersburg, Indiana, United States

Research Site 10001-040

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Valparaiso, Indiana, United States

Research Site 10001-074

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West Des Moines, Iowa, United States

Research Site 10001-107

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Owensboro, Kentucky, United States

Research Site 10001-041

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Lake Charles, Louisiana, United States

Research Site 10001-144

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Crowley, Louisiana, United States

Research Site 10001-101

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Monroe, Louisiana, United States

Research Site 10001-095

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Grandville, Michigan, United States

Research Site 10001-078

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Sterling Heights, Michigan, United States

Research Site 10001-034

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Troy, Michigan, United States

Research Site 10001-018

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Edina, Minnesota, United States

Research Site 10001-156

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Saint Louis, Missouri, United States

Research Site 10001-056

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Saint Paul, Minnesota, United States

Research Site 10001-007

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Saint Louis, Missouri, United States

Research Site 10001-042

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New Windsor, New York, United States

Research Site 10001-055

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Raritan, New Jersey, United States

Research Site 10001-129

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Poughkeepsie, New York, United States

Research Site 10001-122

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Binghamton, New York, United States

Research Site 10001-128

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Endwell, New York, United States

Research Site 10001-110

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Williamsville, New York, United States

Research Site 10001-063

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Cary, North Carolina, United States

Research Site 10001-064

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Greensboro, North Carolina, United States

Research Site 10001-145

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Mooresville, North Carolina, United States

Research Site 10001-016

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Akron, Ohio, United States

Research Site 10001-046

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Shelby, North Carolina, United States

Research Site 10001-141

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Dayton, Ohio, United States

Research Site 10001-148

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Marion, Ohio, United States

Research Site 10001-017

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Edmond, Oklahoma, United States

Research Site 10001-109

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Wyomissing, Pennsylvania, United States

Research Site 10001-001

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Anderson, South Carolina, United States

Research Site 10001-006

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Greer, South Carolina, United States

Research Site 10001-075.

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Greer, South Carolina, United States

Research Site 10001-111

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Myrtle Beach, South Carolina, United States

Research Site 10001-026

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Spartanburg, South Carolina, United States

Research Site 10001-133

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Pelzer, South Carolina, United States

Research Site 10001-103

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Rapid City, South Dakota, United States

Research Site 10001-130

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Kingsport, Tennessee, United States

Research Site 10001-146

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Athens, Tennessee, United States

Research Site 10001-118

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Knoxville, Tennessee, United States

Research Site 10001-100

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Amarillo, Texas, United States

Research Site 10001-009

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Dallas, Texas, United States

Research Site 10001-068

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Edinburg, Texas, United States

Research Site 10001-088

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Houston, Texas, United States

Research Site 10001-032

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Houston, Texas, United States

Research Site 10001-025

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Lubbock, Texas, United States

Research Site 10001-057

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New Braunfels, Texas, United States

Research Site 10001-106

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Powell, Texas, United States

Research Site 10001-079

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Round Rock, Texas, United States

Research Site 10001-045

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Tomball, Texas, United States

Research Site 10001-149

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Shavano Park, Texas, United States

Research Site 10001-005

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Layton, Utah, United States

Research Site 10001-093

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Falls Church, Virginia, United States

Research Site 10001-085

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Manassas, Virginia, United States

Research Site 10001-094

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Midlothian, Virginia, United States

Research Site 10001-029

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Suffolk, Virginia, United States

Research Site 10001-077

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Mesa, Arizona, United States

Research Site 10001-114

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Tacoma, Washington, United States

Research Site 10001-065

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El Cajon, California, United States

Research Site 10001-060

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Bridgewater, New Jersey, United States

Research Site 10001-083

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Schertz, Texas, United States

Research Site 10001-126

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Fort Worth, Texas, United States

Research Site 10001-024

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Flint, Michigan, United States

Research Site 10001-137

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Dunwoody, Georgia, United States

Research Site 10001-054

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Albany, New York, United States

Research Site 10001-033

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Sacramento, California, United States

Research Site 10001-038

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Tampa, Florida, United States

Research Site 10001-143

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Tampa, Florida, United States

Research Site 10001-087

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Austin, Texas, United States

Research Site 10001-023

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Richmond, Virginia, United States

Research Site 10001-117

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Austin, Texas, United States

Research Site 10001-125

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Lexington, Kentucky, United States

Research Site 10001-108

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Lexington, Kentucky, United States

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