MedPath

Study Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis

Phase 3
Completed
Conditions
Compensated Cirrhosis
Nonalcoholic Steatohepatitis
Interventions
Drug: Obeticholic acid (10 mg)
Drug: Obeticholic acid (10 mg to 25 mg)
Drug: Placebo
Registration Number
NCT03439254
Lead Sponsor
Intercept Pharmaceuticals
Brief Summary

The primary objective of this study is to evaluate whether obeticholic acid (OCA; INT-747) can lead to histological improvement in fibrosis with no worsening of NASH in adults with compensated cirrhosis due to NASH.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
919
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Obeticholic Acid (OCA) 10 mgObeticholic acid (10 mg)10 mg OCA for up to 18 months
Obeticholic Acid (OCA) 10 mg to 25 mgObeticholic acid (10 mg to 25 mg)10 mg OCA for the first 3 months and then may titrate up to 25 mg OCA for the remaining 15 months of the study
PlaceboPlaceboPlacebo for up to 18 months
Primary Outcome Measures
NameTimeMethod
DB Phase: Number of Participants Who Were Responders and Showed Improvement in Fibrosis by at Least 1 Stage Without Worsening of Nonalcoholic Steatohepatitis (NASH)Up to 18 months

Fibrosis stage was evaluated by NASH Clinical Research Network(CRN)Fibrosis Staging System with stages:0=no fibrosis;1=perisinusoidal/periportal;1A=mild,zone 3,perisinusoidal;1B=moderate,zone 3,perisinusoidal;1C=portal/periportal;2=perisinusoidal and portal/periportal;3=bridging fibrosis;4=cirrhosis.No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant nonalcoholic fatty liver disease activity score (NAS) categories.NAS is semiquantitative scoring system based on unweighted sum of:steatosis (0=\<5% to 3=\>66%),lobular inflammation(0=no foci to 3=\>4 foci/200x),hepatocellular ballooning(0=none to 2=many cells/prominent ballooning)scores.Total scale range:0-12;0:no features of fatty liver disease and 12:highest degree of fatty liver disease.Higher scores:worse symptoms.Responders:did not discontinue treatment due to Adverse event(AE) or did not die and had evaluable post-Baseline biopsy assessment

OLE Phase: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)Up to 12 months

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

OLE Phase: Change From Baseline to Month 12 in Liver Stiffness Measurement (LSM)Baseline and up to Month 12

Non-invasive radiological methods to assess liver stiffness were conducted at selected study sites where the respective devices were available. These assessments were taken by vibration controlled transient elastography (TE) method using FibroScan®. Participant was included as a random effect and an unstructured covariance matrix was used assuming convergence could be attained. Baseline was defined as the last value collected prior to the first administration of the investigational product (IP). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

OLE Phase: Fibrosis-4 (FIB-4) at BaselineBaseline (Day 1)

FIB-4 was a noninvasive assessment of liver disease assessed by a combination of age, alanine aminotransferase (ALT) and platelet results. FIB-4 was the ratio of age in years and aminotransferase to platelet count. It was a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, ALT, Aspartate aminotransferase (AST) and age that was calculated using formula: FIB-4 = (Age \[years\] x AST \[Units per Liter {U/L}\]) / (platelets \[10\^9/L\] x (square root of ALT \[U/L\])). A FIB-4 index of \<1.45 indicated no or moderate fibrosis and an index of \> 3.25 indicated extensive fibrosis/cirrhosis. Higher ratio indicated worse condition. Baseline was defined as the last value collected prior to the first administration of the IP.

OLE Phase: Enhanced Liver Fibrosis (ELF) at BaselineBaseline (Day 1)

ELF was non-invasive panel of circulating fibrosis markers calculated from serum biomarkers. The markers of fibrosis comprised hyaluronic acid (HA), tissue inhibitor of metalloproteinase (TIMP1) and procollagen III N-terminal peptide (PIIINP). Each of these markers was measured by an immunoassay and an ELF score was generated, from which a level of fibrosis severity could be determined. The ELF test was a composite score: \< 7.7: no to mild fibrosis; ≥ 7.7 - \< 9.8: Moderate fibrosis; ≥ 9.8 - \< 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis.; higher ELF scores were associated with worsening liver fibrosis. Baseline was defined as the last value collected prior to the first administration of the IP.

OLE Phase: Number of Participants Reporting All-cause MortalityUp to Month 12

All-cause mortality is defined as death due to any cause. Number of participants reporting all-cause mortality is presented

OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Ascites, Hepatocellular Carcinoma (HCC) and Non-liver Related DeathUp to 12 months

Adjudication was performed under the review of Hepatic Safety Adjudication Committee (HSAC) of all available data for each identified participant to determine liver injury status. Number of participants with adjudicated liver related clinical outcomes for the following is presented: Ascites (secondary to cirrhosis and requiring medical intervention), Hepatocellular carcinoma (HCC) and non-liver related death.

OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Worsening of Child-Pugh ScoreUp to 12 months

The Child-Pugh classification was a scoring system used for the classification of the severity of cirrhosis. It included three continuous variables (bilirubin, albumin, and international normalized ratio) and two discrete variables (ascites and encephalopathy). Each variable was scored 1-3 with 3 indicating most severe derangement. The determination of Child-Pugh score ranged from 5 to 15. The higher the score, the sicker the participant. Adjudication was performed under the review of HSAC of all available data for each identified participant to determine liver injury status. Number of participants with adjudicated liver related clinical outcomes for worsening of Child-Pugh score is presented.

OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Model for End-Stage Liver Disease (MELD) Score ≥15Up to 12 months

MELD was a scoring system for assessing the severity of chronic liver disease and to assess prognosis and suitability for liver transplantation. It uses the participant's values for total bilirubin, serum creatinine, and the international normalized ratio for prothrombin time to predict survival. MELD score ranges from 6 (less ill) to 40 (gravely ill) with scores and mortality probability being: Score 40=71.3% mortality; Scores 30-39=52.6% mortality; Scores 20-29=19.6% mortality; Scores10-19=6.0% mortality; Score 9 or less=1.9% mortality. Higher scores indicated greater disease severity. Adjudication was performed under the review of HSAC of all available data for each identified participant to determine liver injury status. Number of participants with adjudicated liver related clinical outcomes for MELD score ≥15 is presented.

Secondary Outcome Measures
NameTimeMethod
DB Phase: Change From Baseline to Month 18 in LSMBaseline and up to Month 18

Non-invasive radiological methods to assess liver stiffness were conducted at selected study sites where the respective devices were available. These assessments were taken by vibration controlled TE method using FibroScan®. Participant was included as a random effect and an unstructured covariance matrix was used assuming convergence could be attained. The principal comparison was at Month 18. Baseline was defined as the last value collected prior to the first administration of the IP. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

DB Phase: ELF at BaselineBaseline (Day 1)

ELF was non-invasive panel of circulating fibrosis markers calculated from serum biomarkers. The markers of fibrosis comprised HA, TIMP1 and PIIINP. Each of these markers was measured by an immunoassay and an ELF score was generated, from which a level of fibrosis severity could be determined. The ELF test was a composite score: \< 7.7: no to mild fibrosis; ≥ 7.7 - \< 9.8: Moderate fibrosis; ≥ 9.8 - \< 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis.; higher ELF scores were associated with worsening liver fibrosis. Baseline was defined as the last value collected prior to the first administration of the IP.

DB Phase: FIB-4 at BaselineBaseline (Day 1)

FIB-4 was a noninvasive assessment of liver disease assessed by a combination of age, ALT and platelet results. FIB-4 was the ratio of age in years and aminotransferase to platelet count. It was a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, ALT, AST and age that was calculated using formula: FIB-4 = (Age \[years\] x AST \[U/L\]) / (platelets \[10\^9/L\] x (square root of ALT \[U/L\])). A FIB-4 index of \<1.45 indicated no or moderate fibrosis and an index of \> 3.25 indicated extensive fibrosis/cirrhosis. Higher ratio indicated worse condition. Baseline was defined as the last value collected prior to the first administration of the IP.

Trial Locations

Locations (189)

UT Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

The Ohio State University Wexner Medical Center

🇺🇸

Columbus, Ohio, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Sierra Clinical Research

🇺🇸

Las Vegas, Nevada, United States

Keck Hospital of USC

🇺🇸

Los Angeles, California, United States

Cedars-Sinani Medical Center

🇺🇸

Los Angeles, California, United States

Hi Tech and Global Research LLC

🇺🇸

Coral Gables, Florida, United States

eStudySite

🇺🇸

La Mesa, California, United States

University of California, San Francisco-Fresno

🇺🇸

Fresno, California, United States

Hope Clinical Research

🇺🇸

Canoga Park, California, United States

Inland Empire Liver Foundation

🇺🇸

Rialto, California, United States

Nature Coast Clinical Research

🇺🇸

Inverness, Florida, United States

Innovative Medical Research of South Florida, Inc.

🇺🇸

Aventura, Florida, United States

University at Buffalo, Clinical and Translational Research Center

🇺🇸

Buffalo, New York, United States

Louisiana Research Center

🇺🇸

Shreveport, Louisiana, United States

Florida Medical Clinic, P.A

🇺🇸

Zephyrhills, Florida, United States

UMass Memorial Health Care

🇺🇸

Worcester, Massachusetts, United States

Rutgers New Jersey Medical School

🇺🇸

Newark, New Jersey, United States

Schiff Center for Liver Diseases/University of Miami

🇺🇸

Miami, Florida, United States

Mayo Clinic Florida

🇺🇸

Jacksonville, Florida, United States

South Denver Gastroenterology, PC

🇺🇸

Englewood, Colorado, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

UF Health Jacksonville-Gastroenterology Emerson

🇺🇸

Jacksonville, Florida, United States

Delta Research Partners, LLC

🇺🇸

Monroe, Louisiana, United States

Carolinas Center for Liver Disease/Carolinas HealthCare System

🇺🇸

Huntersville, North Carolina, United States

Diabetes & Endocrinology Consultants, PC

🇺🇸

Morehead City, North Carolina, United States

Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinical Research Center

🇺🇸

Wyoming, Michigan, United States

The Emory Clinic (TEC)

🇺🇸

Atlanta, Georgia, United States

Grand Teton Research Group, PLLC

🇺🇸

Idaho Falls, Idaho, United States

Southern Therapy and Advanced Research (STAR) LLC

🇺🇸

Jackson, Mississippi, United States

Ichan School of Medicine at Mount Sinai Beth Israel

🇺🇸

New York, New York, United States

Huron Gastroenterology Associates

🇺🇸

Ypsilanti, Michigan, United States

Asheville Gastroenterology Associates, P.A.

🇺🇸

Asheville, North Carolina, United States

Charité - Universitätsmedzin Berlin

🇩🇪

Berlin, Germany

The Liver Institute at Methodist Dallas Medical Center

🇺🇸

Dallas, Texas, United States

The University of Texas Medical School at Houston

🇺🇸

Houston, Texas, United States

Charlotte Gastroenterology & Hepatology, PLLC

🇺🇸

Charlotte, North Carolina, United States

Trial Management Associates, LLC

🇺🇸

Wilmington, North Carolina, United States

Associates in Gastroenterology, PLC

🇺🇸

Hermitage, Tennessee, United States

CHU Amiens Picardie

🇫🇷

Amiens, France

Liver Center of Texas

🇺🇸

Dallas, Texas, United States

Gastro One

🇺🇸

Germantown, Tennessee, United States

Gastroenterology Consultants of Southwest Virginia

🇺🇸

Roanoke, Virginia, United States

Mater Misericordiae Limited

🇦🇺

South Brisbane, Queensland, Australia

Hôpital Beaujon- Service d'Hepatologie

🇫🇷

Clichy, France

Virginia Mason - Seattle Medical Center

🇺🇸

Seattle, Washington, United States

Royal Adelaide Hospital

🇦🇺

Adelaide, South Australia, Australia

The Pennsylvania State University and the Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

Baylor College of Medicine - Advanced Liver Therapies

🇺🇸

Houston, Texas, United States

University of Calgary Liver Unit (Heritage Medical Research Clinic)

🇨🇦

Calgary, Alberta, Canada

Centex Studies, Inc.

🇺🇸

McAllen, Texas, United States

Digestive and Liver Disease Specialists

🇺🇸

Norfolk, Virginia, United States

Baylor Scott and White All Saints Medical Center

🇺🇸

Fort Worth, Texas, United States

Queen Elizabeth II Health Sciences Centre, Nova Scotia Health Authority

🇨🇦

Halifax, Nova Scotia, Canada

Harborview Medical Center

🇺🇸

Seattle, Washington, United States

Royal Melbourne Hospital

🇦🇺

Parkville, Victoria, Australia

Kent Place

🇨🇦

Lindsay, Ontario, Canada

Chronic Viral Illness/McGill University Health Centre (MUHC)

🇨🇦

Montreal, Quebec, Canada

Texas Digestive Disease Consultants

🇺🇸

San Marcos, Texas, United States

Flinders Medical Centre

🇦🇺

Bedford Park, South Australia, Australia

Nepean Blue Mountains Local Health District, Nepean Hospital

🇦🇺

Kingswood, New South Wales, Australia

London Health Sciences Centre-University Hospital

🇨🇦

London, Ontario, Canada

The University of Vermont Medical Center

🇺🇸

Burlington, Vermont, United States

Austin Health

🇦🇺

Heidelberg, Victoria, Australia

Maryview Hospital, Inc. d/b/a Bon Secours Liver Institute of Hampton Roads

🇺🇸

Newport News, Virginia, United States

Universitätsmedizin Mainz

🇩🇪

Mainz, Rheinland-Pfalz, Germany

Synexus Polska Sp. z o.o., Oddział w Częstochowie

🇵🇱

Częstochowa, Poland

Fundación de Investigación de Diego

🇵🇷

San Juan, Puerto Rico

Univeritätsklinkum Würzburg

🇩🇪

Würzburg, Bayern, Germany

Center Hospitalier Universitaire Grenoble Alpes

🇫🇷

La Tronche, France

Teuber Consulting & Research UG

🇩🇪

Frankfurt am main, Hessen, Germany

Kyiv Railway Clinical Hospital №2 of branch "Health Center" of the Joint-Stock Company "Ukranian Railway", Day treatment department

🇺🇦

Kyiv, Ukraine

Hospital General Universitario de Valencia

🇪🇸

Valencia, Spain

CHRU de Nancy - Hôpitaux de Brabois

🇫🇷

Vandoeuvre-les-Nancy, France

Hospital Universitari i Politécnic La Fe

🇪🇸

Valencia, Spain

Hôpital de la Croix Rousse

🇫🇷

Lyon Cedex 04, France

Hôpital Paul Brousse

🇫🇷

Villejuif, France

Universitätsklinikum Leipzig AöR

🇩🇪

Leipzig, Sachsen, Germany

Latin Clinical Trial Center

🇵🇷

San Juan, Puerto Rico

Hospital Clínic de Barcelona

🇪🇸

Barcelona, Spain

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Hôpital Purpan

🇫🇷

Toulouse, France

EUGASTRO GmbH

🇩🇪

Leipzig, Sachsen, Germany

CHU de Rouen-Centre Hospitalier Universitaire

🇫🇷

Rouen, France

Middlemore Hospital

🇳🇿

Auckland, New Zealand

Hospital Universitario Puerta de Hierro Majadahonda

🇪🇸

Madrid, Spain

Kansas Medical Clinic

🇺🇸

Topeka, Kansas, United States

Gastroenterologisch-Hepatologisches Zentrum Kiel

🇩🇪

Kiel, Schleswig-Holstein, Germany

University of California, San Francisco

🇺🇸

San Francisco, California, United States

Quaility Medical Research, PLLC

🇺🇸

Nashville, Tennessee, United States

Vanderbilt University Medical Center - Digestive Disease Center

🇺🇸

Nashville, Tennessee, United States

American Research Corporation

🇺🇸

San Antonio, Texas, United States

Clinical Trials of Texas, Inc.

🇺🇸

San Antonio, Texas, United States

University of Mississippi Medical Center

🇺🇸

Jackson, Mississippi, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

University Hospitals Birmingham NHS Foundation Trust

🇬🇧

Birmingham, England, United Kingdom

Synexus Polska Sp. Z.o.o., Oddział w Gdyni

🇵🇱

Gdynia, Poland

Synexus Polska Sp. z o.o., Oddział w Wrocławiu

🇵🇱

Wrocław, Poland

Derriford Hospital

🇬🇧

Plymouth, England, United Kingdom

Nottingham University Hospitals NHS Trust

🇬🇧

Nottingham, England, United Kingdom

NYU Langone Health

🇺🇸

New York, New York, United States

Synexus Magyarország Kft. Budapest

🇭🇺

Budapest, Hungary

Synexus Polska Sp. z.o.o., Oddział w Gdańsku

🇵🇱

Gdańsk, Poland

Synexus Polska Sp. z o.o., Oddział w Łodzi

🇵🇱

Łódź, Poland

Oxford University Hospitals NHS Foundation Trust

🇬🇧

Oxford, Oxfordshire, United Kingdom

Synexus Polska Sp. z o.o., Oddział w Katowicach

🇵🇱

Katowice, Poland

Synexus Polska Sp. z o.o., Oddział w Warszawie

🇵🇱

Warszawa, Poland

Royal Free Hospital NHS Foundation Trust

🇬🇧

London, England, United Kingdom

Derby Teaching Hospitals NHS Foundation Trust

🇬🇧

Derby, Derbyshire, United Kingdom

Imperial College Healthcare NHS Trust, St Mary's Hospital

🇬🇧

London, England, United Kingdom

King's College Hospital NHS Foundation Trust

🇬🇧

London, England, United Kingdom

CHU de Nice, Hôpital de l'Archet 2

🇫🇷

Nice, France

Centre Hospitalier Universitaire d'Angers

🇫🇷

Angers, France

Toronto Liver Centre

🇨🇦

Toronto, Ontario, Canada

Office of Dr. Gauthier

🇨🇦

North Bay, Ontario, Canada

CHI Health Alegent Creighton Clinic

🇺🇸

Omaha, Nebraska, United States

St Vincent's Hospital

🇦🇺

Fitzroy, Victoria, Australia

University of Colorado Denver and Hospital

🇺🇸

Aurora, Colorado, United States

Guardian Angel Research Center, INC

🇺🇸

Tampa, Florida, United States

Walter Reed National Military Medical Center

🇺🇸

Bethesda, Maryland, United States

Gastrointestinal Specialists of Georgia

🇺🇸

Marietta, Georgia, United States

Amici GI-LLC

🇺🇸

Martinsville, New Jersey, United States

Christchurch Hospital

🇳🇿

Christchurch, New Zealand

Liver Wellness Center

🇺🇸

Little Rock, Arkansas, United States

Arizona Liver Health

🇺🇸

Glendale, Arizona, United States

Arkansas Gastroenterology

🇺🇸

North Little Rock, Arkansas, United States

Objective GI d/b/a North Alabama GI Research Center

🇺🇸

Madison, Alabama, United States

The Institute for Liver Health

🇺🇸

Tucson, Arizona, United States

Scripps Whittier Diabetes Institute

🇺🇸

La Jolla, California, United States

Palmtree Clinical Research, INC.

🇺🇸

Palm Springs, California, United States

Stanford University Medical Center

🇺🇸

Palo Alto, California, United States

California Liver Research Institute

🇺🇸

Pasadena, California, United States

Peak Gastroenterology Associates

🇺🇸

Colorado Springs, Colorado, United States

Gastroenterology Associates of Pensacola, PA

🇺🇸

Pensacola, Florida, United States

Sensible Healthcare, LLC

🇺🇸

Ocoee, Florida, United States

Innovation Medical Research Center

🇺🇸

Palmetto Bay, Florida, United States

Tampa General Medical Group

🇺🇸

Tampa, Florida, United States

Summit Clinical Research, LLC

🇺🇸

Athens, Georgia, United States

Loyola University Medical Center

🇺🇸

Maywood, Illinois, United States

Aquiant Research

🇺🇸

New Albany, Indiana, United States

Mercy Medical Center

🇺🇸

Baltimore, Maryland, United States

Lahey Hospital & Medical Center

🇺🇸

Burlington, Massachusetts, United States

Minnesota Gastroenterology, P.A.

🇺🇸

Saint Paul, Minnesota, United States

Weill Cornell Medical College

🇺🇸

New York, New York, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Dayton Gastroenterology, Inc.

🇺🇸

Beavercreek, Ohio, United States

Northeast Clinical Research Center, LLC

🇺🇸

Bethlehem, Pennsylvania, United States

Carolinas Health Care System Center for Liver Disease

🇺🇸

Huntersville, North Carolina, United States

UPMC - Center for Liver Diseases at the Thomas E. Starzl Institute

🇺🇸

Pittsburgh, Pennsylvania, United States

Einstein Healthcare Network

🇺🇸

Philadelphia, Pennsylvania, United States

University Gastroenterology

🇺🇸

Providence, Rhode Island, United States

Methodist Healthcare University Hospital

🇺🇸

Memphis, Tennessee, United States

Johnson City Medical Center

🇺🇸

Johnson City, Tennessee, United States

Texas Clinical Research Institute LLC

🇺🇸

Arlington, Texas, United States

Rapid City Medical Center LLP

🇺🇸

Rapid City, South Dakota, United States

San Antonio Military Medical Center

🇺🇸

Fort Sam Houston, Texas, United States

University of Washington Medical Center

🇺🇸

Seattle, Washington, United States

(G.I.R.I.) GI Research Institute

🇨🇦

Vancouver, British Columbia, Canada

Clinique de medecine Urbaine du Quartier Latin

🇨🇦

Montréal, Quebec, Canada

Centre Hospitalier Universitaire de Strasbourg

🇫🇷

Strasbourg, France

Hôpital Pitié-Salpêtrierè

🇫🇷

Paris, France

Hôpital Hautepierre

🇫🇷

Strasbourg, France

Universitätsklinikum Hamburg Eppendorf

🇩🇪

Hamburg, Germany

Synexus Magyarorszag Kft. Debrecen A.S.

🇭🇺

Debrecen, Hungary

Synexus Magyarorszag Kft. Gyula DRS

🇭🇺

Gyula, Hungary

Dunedin Public Hospital

🇳🇿

Dunedin, New Zealand

Wellington Regional Hospital

🇳🇿

Wellington, New Zealand

Synexus Polska Sp. z o.o., Oddział w Poznaniu

🇵🇱

Poznań, Poland

Hospital Universitario Marqués de Valdecilla

🇪🇸

Santander, Spain

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Spain

Medical Center of LLC Medbud-Clinic, Clinical Diagnostic Department

🇺🇦

Kyiv, Ukraine

The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital

🇬🇧

Newcastle Upon Tyne, Tyne And Wear, United Kingdom

Digestive Health Specialists of the Southeast

🇺🇸

Dothan, Alabama, United States

Tandem Clinical Research, LLC

🇺🇸

Marrero, Louisiana, United States

University of California, Davis Medical Center

🇺🇸

Sacramento, California, United States

Kaiser Permanente Sacramento Medical Center

🇺🇸

Sacramento, California, United States

University of Louisville, Clinical Trials Unit

🇺🇸

Louisville, Kentucky, United States

Tulane University Health Sciences Center

🇺🇸

New Orleans, Louisiana, United States

Kansas City Research Institute

🇺🇸

Kansas City, Missouri, United States

University of North Carolina at Chapel Hill, School of Medicine

🇺🇸

Chapel Hill, North Carolina, United States

Ralph H. Johnson Veterans Affairs Medical Center

🇺🇸

Charleston, South Carolina, United States

SCTR Research Nexus

🇺🇸

Charleston, South Carolina, United States

Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours

🇺🇸

Richmond, Virginia, United States

McGuire VA Medical Center

🇺🇸

Richmond, Virginia, United States

Virginia Commonwealth University

🇺🇸

Richmond, Virginia, United States

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

Thomas Jefferson University

🇺🇸

Philadelphia, Pennsylvania, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

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