Phase 4 Study of Obeticholic Acid Evaluating Clinical Outcomes in Patients With Primary Biliary Cholangitis

NCT ID: NCT02308111

Last Updated: 2023-03-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 334 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-26
• Study Completion Date: 2021-12-23

Brief Summary

Primary Biliary Cholangitis (PBC) is a serious, life-threatening, bile acid related liver disease of unknown cause. Without treatment, it frequently progresses to liver fibrosis and eventual cirrhosis requiring liver transplantation or resulting in death. The investigational drug, Obeticholic Acid (OCA) is a modified bile acid and FXR agonist that is derived from the primary human bile acid chenodeoxycholic acid. The key mechanisms of action of OCA, including its choleretic, anti-inflammatory, and anti-fibrotic properties, underlie its hepatoprotective effects and result in attenuation of injury and improved liver function in a cholestatic liver disease such as PBC. The study will assess the effect of OCA compared to placebo, combined with stable standard care, on clinical outcomes in PBC participants.

Detailed Description

This Phase 4, double-blind, randomized, placebo-controlled, multicenter study is being undertaken at up to 170 sites internationally to evaluate the effect of OCA on clinical outcomes in 428 participants with PBC. The study will include a screening period of up to 8 weeks, requiring two clinic visits. Eligible participants will be randomly allocated (1:1) to treatment with either OCA 5 mg or matching placebo tablets, taken orally once daily for the majority of participants; dose and frequency will be modified for participants with cirrhosis and classified as Child-Pugh (CP) B or C. Randomization will be stratified by standard treatment with UDCA (yes/no) and baseline liver function. The treatment period involves clinic visits approximately every 3 months. At the 3 month visit or any study visit thereafter, if study treatment is tolerated, participants' dose should be titrated per protocol in a blinded manner eg for participants who are non-cirrhotic or classified as CP A and randomized to OCA, they should receive the maximum daily dose of 10 mg OCA, those on placebo continue to receive placebo. Subsequently, daily dosage may return to 5 mg if necessary for these participants who are non-cirrhotic or classified as CP A, but should be increased to 10 mg if possible, based on tolerability and clinical judgment. Safety and tolerability will be assessed by monitoring adverse events and vital signs, and blood and urine testing. The study is event driven and total duration will be determined by the time required to accrue approximately 127 primary endpoint events, estimated to be approximately 10 years. Participants are expected to have a minimum follow-up time of approximately 6 years.

Conditions

Liver Cirrhosis, Biliary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Obeticholic Acid (OCA) 5 mg to 10 mg

Obeticholic Acid (OCA) 5 mg for a minimum 3 months and then titrating up to a maximum 10 mg for the remainder of the trial (based on tolerability and CP Score).

Group Type: EXPERIMENTAL

Obeticholic Acid (OCA)

Intervention Type: DRUG

Non-cirrhotic and classified as CP Class A: 5 mg tablet of OCA once daily titrating up to a maximum of 10 mg OCA once daily based on tolerability at 3 months for the duration of the study (majority of participants).

Cirrhotic and classified as CP Class B and C: 5 mg tablet of OCA once weekly for at least 3 months, subsequently titrating up to a maximum dose and frequency of 10 mg OCA twice weekly based on tolerability and biochemical response for the duration of the study.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One tablet daily (or a lower frequency depending on CP score) for the remainder of the study

Interventions

Obeticholic Acid (OCA)

Non-cirrhotic and classified as CP Class A: 5 mg tablet of OCA once daily titrating up to a maximum of 10 mg OCA once daily based on tolerability at 3 months for the duration of the study (majority of participants).

Cirrhotic and classified as CP Class B and C: 5 mg tablet of OCA once weekly for at least 3 months, subsequently titrating up to a maximum dose and frequency of 10 mg OCA twice weekly based on tolerability and biochemical response for the duration of the study.

Intervention Type: DRUG

Placebo

One tablet daily (or a lower frequency depending on CP score) for the remainder of the study

Intervention Type: DRUG

Other Intervention Names

6alpha-ethylchenodeoxycholic acid (6-ECDCA); INT-747

Eligibility Criteria

Inclusion Criteria

1. Definite or probable PBC diagnosis (consistent with American Association for the Study of Liver Diseases [AASLD] and the European Association for the Study of the Liver [EASL] practice guidelines; Lindor 2009; EASL 2009), as demonstrated by the presence of ≥2 of the following 3 diagnostic factors:

• History of elevated Alkaline phosphatase levels for at least 6 months
• Positive antimitochondrial antibody (AMA) titer or if AMA negative or in low titer (<1:80) PBC-specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex])
• Liver biopsy consistent with PBC

2. A mean total bilirubin >ULN and ≤5x ULN and/or a mean ALP >3x ULN

3. Either is not taking UDCA (no UDCA dose in the past 3 months) or has been taking UDCA for at least 12 months with a stable dose for ≥3 months prior to Day 0

Exclusion Criteria

1. History or presence of other concomitant liver diseases including:

• Hepatitis C virus infection
• Active Hepatitis B infection; however, subjects who have seroconverted (hepatitis B surface antigen and hepatitis B e antigen negative) may be included in this study after consultation with the medical monitor
• Primary sclerosing cholangitis (PSC)
• Alcoholic liver disease
• Definite autoimmune liver disease or overlap hepatitis
• Nonalcoholic steatohepatitis (NASH)
• Gilbert's Syndrome

2. Presence of clinical complications of PBC or clinically significant hepatic decompensation, including:

• Cirrhosis with complications, including history (within the past 12 months) or presence of:

• Variceal bleed
• Uncontrolled ascites
• Encephalopathy
• Spontaneous bacterial peritonitis
• Known or suspected HCC
• Prior transjugular intrahepatic portosystemic shunt procedure
• Hepatorenal syndrome (type I or II) or screening (Visit 1 or 2) serum creatinine >2 mg/dL (178 μmol/L)

3. Mean total bilirubin >5x ULN

4. Subjects who have undergone gastric bypass procedures (gastric lap band is acceptable) or ileal resection or plan to undergo either of these procedures

5. Other medical conditions that may diminish life expectancy, including known cancers (except carcinomas in situ or other stable, relatively benign conditions)

6. If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating

7. Known history of human immunodeficiency virus infection

8. Medical conditions that may cause nonhepatic increases in ALP (eg, Paget's disease or fractures within 3 months)

9. Other clinically significant medical conditions that are not well controlled or for which medication needs are anticipated to change during the study

10. History of alcohol abuse or other substance abuse within 1 year prior to Day 0

11. Participation in another investigational product, biologic, or medical device study within 30 days prior to Screening. Participation in a previous study of OCA is allowed with 3 months washout prior to enrollment in this study

12. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain

13. History of known or suspected clinically significant hypersensitivity to OCA or any of its components

14. UDCA naïve (unless contraindicated)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Intercept Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Erik Ness, MD

Role: STUDY_DIRECTOR

Intercept Pharmaceuticals

Locations

Mayo Clinic Arizona

Phoenix, Arizona, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

Inland Empire Liver Foundation

Rialto, California, United States

University of California Davis, Davis Medical Center

Sacramento, California, United States

Stanford University

Stanford, California, United States

University of Colorado Denver and Hospital

Aurora, Colorado, United States

UF Hepatology Research at CTRB

Gainesville, Florida, United States

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, United States

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Gastrointestinal Specialists of Georgia

Marietta, Georgia, United States

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

Indianapolis Gastroenterology Research Foundation

Indianapolis, Indiana, United States

University of Louisville, Medical Dental Complex

Louisville, Kentucky, United States

Tulane University Medical Center

New Orleans, Louisiana, United States

Mercy Medical Center

Baltimore, Maryland, United States

UMass Medical School

Worcester, Massachusetts, United States

Henry Ford Health System

Novi, Michigan, United States

Minnesota Gastroenterology, P.A.

Saint Paul, Minnesota, United States

Southern Therapy and Advanced Research (STAR)

Jackson, Mississippi, United States

Kansas City Research Institute

Kansas City, Missouri, United States

Saint Louis University Gastroenterology & Hepatology

St Louis, Missouri, United States

Saint Joseph's Regional Medical Center

Paterson, New Jersey, United States

Mount Sinai Beth Israel

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Quality Medical Research, PLLC

Nashville, Tennessee, United States

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, United States

Baylor University Medical Center

Dallas, Texas, United States

Texas Digestive Disease Consultants

Dallas, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Baylor Scott and White Research Institute

Fort Worth, Texas, United States

Baylor College of Medicine - Advanced Liver Therapies

Houston, Texas, United States

UT Health The University of Texas Health Science Center at Houston

Houston, Texas, United States

American Research Corporation at Texas Liver Institute

San Antonio, Texas, United States

Texas Digestive Disease Consultants

Southlake, Texas, United States

Clinical Research Centers of America

Murray, Utah, United States

McGuire DVAMC

Richmond, Virginia, United States

Swedish Organ Transplant & Liver Center

Seattle, Washington, United States

Centro De Hepatología

La Plata, Buenos Aires, Argentina

Hospital Universitario Austral

Presidente Derqui, Buenos Aires, Argentina

Dim Clínica Privada

Ramos Mejía, Buenos Aires, Argentina

Hospital Privado Universitario de Cordoba S.A.

Córdoba, Córdoba Province, Argentina

Hospital Provincial del Centenario

Rosario, Santa Fe Province, Argentina

CIPREC - Centro de Investigacion y Prevencion Cardiovascular S.A.

Buenos Aires, , Argentina

Hospital De Clinicas University Of Buenos Aires

Buenos Aires, , Argentina

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo

Buenos Aires, , Argentina

Centrol Integral de Gastroenterologia

Buenos Aires, , Argentina

Hospital Aleman

Buenos Aires, , Argentina

Hospital Britanico De Buenos Aires

Buenos Aires, , Argentina

AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Department of Gastroenterology & Hepatology, Nepean Hospital

Kingswood, New South Wales, Australia

Gallipoli Medical Research Foundation

Brisbane, Queensland, Australia

Department of Gastroenterology and Hepatology, Royal Adelaide Hospital

Adelaide, South Australia, Australia

Flinders Medical Centre

Adelaide, South Australia, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

St. Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Fiona Stanley Hospital, Gastroenterology Department

Murdoch, Western Australia, Australia

AKH, Medical University of Vienna

Vienna, , Austria

University Hospital Antwerp

Edegem, Antwerp, Belgium

Uz Leuven

Leuven, Vlaams-Brabant, Belgium

Cub Hôpital Erasme

Brussels, , Belgium

University Hospital Ghent

Ghent, , Belgium

Gastrocentro/ Universidade Estadual de Campinas (UNICAMP)

São Paulo, Campinas, Brazil

Instituto Hospital de Base do Distrito Federal-IHBDF

Brasília, Distrito Federal Brazil, Brazil

Hospital Sao Rafael

São Salvador, Estado de Bahia, Brazil

Instituto Goiano de Gastroenterologia

Goiânia, Goiás, Brazil

Cepec Huufma

São Luís, Maranhão, Brazil

Hospital das Clinicas da Universidade Federal de Minas Gerais (UFMG)

Belo Horizonte, Minas Gerais, Brazil

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Universitario Professor Edgard Santos

Bahia, Salvador, Brazil

Gastrocentro. Unidad Estadual de CAmpinas UNICAMP

Campinas, São Paulo, Brazil

Universidade Federal do Estado do Rio de Janeiro - Hospital Universitario Gaffree e Guinle/HUGG/UNIRIO

Rio de Janeiro, , Brazil

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo-HCFMUSP

São Paulo, , Brazil

St. Ivan Rilsky University Hospital

Sofia, , Bulgaria

University of Calgary Liver Unit (Heritage Medical Research Clinic)

Calgary, Alberta, Canada

University of Alberta, Walter C. Mackenzie Health Sciences Centre (WMC)

Edmonton, Alberta, Canada

University Of Manitoba, Health Sciences Centre

Winnipeg, Manitoba, Canada

London Health Sciences Centre-University Hospital

London, Ontario, Canada

University Health Network, Toronto General Hospital

Toronto, Ontario, Canada

Chum

Montreal, Quebec, Canada

Centro De Investigaciones Clínicas Viña Del Mar

Viña del Mar, Región de Valparaíso, Chile

Aarhus University Hospital Department of Hepatology and Gastroenterology

Aarhus, Aarhus C, Denmark

Medicinsk klinik for mave, tarm-og leversygdomme

København Ø, , Denmark

Odense University Hospital Afdeling for medicinske mave-tarmsygdomme S

Odense, , Denmark

East Tallinn Central Hospital Gastroenterology Center

Tallinn, Harju, Estonia

Tartu University Hospital

Tartu, , Estonia

Helsinki University Central Hospital

Helsinki, , Finland

Turku University Central Hospital, Gastroenterology Outpatient Clinic

Turku, , Finland

Hospital Saint-Antoine, A.P.-H.P.

Paris, Paris, France

CHRU Hôpital HURIEZ

Lille, , France

Chu De Bordeaux - Hôpital Haut Lévêque

Pessac, , France

Klinikum der Johann-Wolfgang Goethe, Universitaet Frankfurt am Main

Frankfurt am Main, Hesse, Germany

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie

Hanover, Lower Saxony, Germany

Friedrich-Alexander-Uniersitat Erlangen

Erlangen, QLD, Germany

CHARITÉ, Campus Virchow Klinikum

Berlin, , Germany

Univeritatsklinikum Hamburg Eppendorf, Medizinische Klinik und Poliklinik

Hamburg, , Germany

Universitaetsklinikum Heidelberg Medizinische Universitaetsklinik

Heidelberg, , Germany

Universität Leipzig KöR, Medizinische Fakultät

Leipzig, , Germany

University of Munich, LMU Klinikum Grosshadern

Munich, , Germany

Queen Mary Hospital

Hong Kong, Pokfulam, Hong Kong

Prince Of Wales Hospital

Hong Kong, Shatin, Hong Kong

Tuen Mun Hospital

Hong Kong, Tuen Mun, New Territories, Hong Kong

Alice Ho Miu Ling Nethersole Hospital

Hong Kong, , Hong Kong

Humanity & Health Research Centre

Hong Kong, , Hong Kong

Békés Megyei Kozponti Korhaz - Dr. Rethy Pal Tagkorhaz

Békéscsaba, , Hungary

Szent János Hospital

Budapest, , Hungary

University Of Debrecen, Department Of Medicine, Division Of Gastroenterology

Debrecen, , Hungary

Hadassah Hebrew University Medical Center

Jerusalem, Nazareth Elit, Israel

Soroka Medical Center

Beersheba, , Israel

Rambam Health Care Campus

Haifa, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Sourasky Tel-Aviv Medical Center

Tel Aviv, , Israel

Azienda Ospedaliero - Universitaria di Cagliari - Centro per lo Studio delle Malattie del Fegato

Monserrato, Cagliari, Italy

Università Politecnica delle Marche - Azienda Ospedaliero

Ancona, , Italy

AOU Policlinico Sant' Orsola Malpighi

Bologna, , Italy

Azienda Ospedaliero Universitaria Sant´ Orsola Malpighi

Bologna, , Italy

Azienda Ospedaliero Universitaria Careggi Universita di Firenze

Florence, , Italy

Azienda Socio-Sanitarla Territoriale (ASST) Santi Paolo e Carlo

Milan, , Italy

AOU Ospedale Civile S. Agostino Estense - UO Medicina Metabolica

Modena, , Italy

Azienda Socio Sanitaria Territoriale (ASST) di Monza

Monza, , Italy

Azienda Ospedaliero - Universita di Padova

Padua, , Italy

AOU Policlinico Paolo Giaccone - Di.Bi.M.I.S

Palermo, , Italy

Policlinico Universitario Agostino Gemelli - Universita Cattolica del Sacro Cuore

Rome, , Italy

Hospital of Lithuanian University of Health Sciences, Kauno klinikos

Kaunas, , Lithuania

Vilnius University Hospital Santaros klinikos

Vilnius, , Lithuania

Departamento De Gastroenterologia. Instituto Nacional De Ciencias Medicas Y Nutricion Salvador Zubiran

Mexico City, Mexico City, Mexico

Medica Sur, S.A.B. de C.V.

Mexico City, Mexico City, Mexico

Consultorio Médico de la Dra Alma Laura Ladrón de Guevara Cetina

Mexico City, Mexico City, Mexico

Radboud UMC

Nijmegen, Gelderland, Netherlands

Vrije Universiteit Medisch Centrum (VUMC)

Amsterdam, North Holland, Netherlands

Erasmus Mc

Rotterdam, South Holland, Netherlands

Amsterdam University Medical Centre (AMC)

Amsterdam, , Netherlands

University Medical Center Utrecht

Utrecht, , Netherlands

NZ Liver Transplant Unit, Auckland Hospital

Grafton, Auckland, New Zealand

Gastroenterology, Christchurch Hospital

Christchurch, Canterbury, New Zealand

Nzoz Vitamed

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Wojewodzki Szpital Specjalistyczny im. J. Gromkowskiego, Pierwszy Oddzial Chorob Zakaznych

Wroclaw, Lover Silesia, Poland

Centrum Onkologii - Instytut im. Marii Skłodowskiej - Curie, Klinika Gastroenterologii Onkologicznej

Warsaw, Masovian Voivodeship, Poland

Medical University of Warsaw Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie (SPCSK in Warsaw

Warsaw, Masovia, Poland

Oddział Gastr. I Hepat. Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibińskiego Sum

Katowice, Silesian Voivodeship, Poland

Dep. Of Gastroenterology UM Lublin

Lublin, , Poland

Centro Hospitalar Lisboa Norte, EPE - Hospital de Santa Maria

Lisbon, , Portugal

Clinic For Gastroenterology And Hepatology Clinical Center Of Serbia

Belgrade, , Serbia

Clinical Hospital Centre Zvezdara

Belgrade, , Serbia

Inje University Busan Paik Hospital

Busan, Busanjin-gu, South Korea

Gangnam Severance Hospital

Seoul, Gangnam-gu, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Seoul National University Hospital

Seoul, Jongno-Gu, South Korea

Pusan National University Hospital

Busan, Seo-gu, South Korea

Hospital Universitario Marqués De Valdecilla

Santander, Cantabria, Spain

Hospital Universitario Puerta De Hierro Majadahonda

Majadahonda, Madrid, Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Virgen De La Victoria University Hospital

Málaga, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

La Fe, Hospital ( Valence )

Valencia, , Spain

Karolinska University Hospital

Stockholm, Huddinge, Sweden

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Inselspital, University Of Bern, UVCM, DMLL

Bern, , Switzerland

Kantonsspital St. Gallen, Clinic for Gastroeterologie and Hepatologie

Sankt Gallen, , Switzerland

USZ, Klinik für Gastroenterologie und Hepatologie

Zurich, , Switzerland

Ankara University School of Medicine Gastroenterology Dept.

Ankara, , Turkey (Türkiye)

Ege University School of Medicine Gastroenterology Dept.

Izmir, , Turkey (Türkiye)

University Hospitals Bristol NHS Foundation Trust

Bristol, Avon, United Kingdom

Plymouth Hospitals NHS Trust, Derriford Hospital

Plymouth, Devon, United Kingdom

Gartnavel General Hospital

Glasgow, Lanarkshire, United Kingdom

Forth Valley Royal Hospital

Larbert, Scotland, United Kingdom

Institute of Cellular Medicine

Newcastle upon Tyne, Tyne and Wear, United Kingdom

University Hospitals Birmingham NHS Foundation Trust

Birmingham, West Midlands, United Kingdom

Cambrigde University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

The Royal Free Hospital

London, , United Kingdom

Nottingham University Hospital Nhs Trust

Nottingham, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Bulgaria; Canada; Chile; Denmark; Estonia; Finland; France; Germany; Hong Kong; Hungary; Israel; Italy; Lithuania; Mexico; Netherlands; New Zealand; Poland; Portugal; Serbia; South Korea; Spain; Sweden; Switzerland; Turkey (Türkiye); United Kingdom

References

Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308. doi: 10.1002/hep.22906. No abstract available.

Reference Type: BACKGROUND

PMID: 19554543 (View on PubMed)

European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009 Aug;51(2):237-67. doi: 10.1016/j.jhep.2009.04.009. Epub 2009 Jun 6. No abstract available.

Reference Type: BACKGROUND

PMID: 19501929 (View on PubMed)

Kowdley KV, Hirschfield GM, Coombs C, Malecha ES, Bessonova L, Li J, Rathnayaka N, Mells G, Jones DE, Trivedi PJ, Hansen BE, Smith R, Wason J, Hiu S, Kareithi DN, Mason AL, Bowlus CL, Muller K, Carbone M, Berenguer M, Milkiewicz P, Adekunle F, Villamil A. COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls. Am J Gastroenterol. 2025 Feb 1;120(2):390-400. doi: 10.14309/ajg.0000000000003029. Epub 2024 Aug 14.

Reference Type: DERIVED

PMID: 39140490 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

747-302

Identifier Type: -

Identifier Source: org_study_id