Comparison of Ridinilazole Versus Vancomycin Treatment for Clostridium Difficile Infection

NCT ID: NCT03595553

Last Updated: 2023-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 759 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-28
• Study Completion Date: 2021-11-17

Brief Summary

Summit is developing ridinilazole as a novel antimicrobial for Clostridioides difficile Infection (CDI), formerly known as Clostridium difficile Infection, with the goal of demonstrating an improved Sustained Clinical Response rate in subjects treated with ridinilazole as compared to subjects treated with vancomycin.

A phase 2 proof of concept study, with vancomycin as comparator, demonstrated these attributes with a comparable safety profile. A high fecal concentration of ridinilazole and little systemic exposure were noted.

The rationale for this phase 3 study is to confirm the improvement in sustained clinical response of CDI over vancomycin and to compare the safety and tolerability of ridinilazole to that of vancomycin.

Ridinilazole plasma concentration will be assessed in a subset of patients.

Conditions

Clostridioides Difficile Infection

Study Design

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

Study Groups

ridinilazole

ridinilazole 200mg bid

Group Type: EXPERIMENTAL

Ridinilazole

Intervention Type: DRUG

ridinilazole (200 mg bid)

vancomycin

vancomycin 125 mg qid

Group Type: ACTIVE_COMPARATOR

Vancomycin

Intervention Type: DRUG

vancomycin (125 mg qid)

Interventions

Ridinilazole

ridinilazole (200 mg bid)

Intervention Type: DRUG

Vancomycin

vancomycin (125 mg qid)

Intervention Type: DRUG

Other Intervention Names

2,2'-di(pyridin-4-yl)-1H,1'H-5,5'-bi(benzimidazole), 2,2'-bis(4-pyridyl)-3H,3'H-5,5'-bibenzimidazole, 2-pyridin-4-yl-6-(2-pyridin-4-yl-3H-benzimidaz

Eligibility Criteria

Inclusion Criteria

Patients are eligible to be included in the study only if all the following criteria apply:

1. Patient must be at least 18 years of age, at the time of signing the informed consent.

2. Have signs and symptoms of CDI including diarrhea such that in the Investigator's opinion, CDI antimicrobial therapy is required. Diarrhea is defined as a change in bowel habits, with ≥3 unformed bowel movements (UBMs) (5, 6 or 7 on the Bristol Stool Chart) in the 24 h prior to randomization.

3. Have the presence of either toxin A and/or B of C. difficile in the stool determined by a positive free toxin test (using a Sponsor agreed test). The stool sample must be current (produced within 72 hours prior to randomization).

4. Male or Female

Male patients:

• A male patient must agree to use contraception as detailed in Section 10.4 of this protocol during the treatment period and for at least 30 days after the last dose of study treatment and refrain from donating sperm during this period.

Female patients:

• A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: i. Not a woman of childbearing potential (WOCBP) OR ii. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment.

5. Has provided documented signed informed consent and any authorizations required by local law (e.g. Protected Health Information [PHI]). If unable to read, understand and sign the informed consent form a legally authorized representative (LAR) may provide consent on the patient's behalf if permitted by the Institutional Review Board (IRB)/Ethics Committee (EC).

Exclusion Criteria

Patients are excluded from the study if any of the following criteria apply:

1. Have had more than one prior episode of CDI in the previous 3 months or more than 3 episodes in the past 12 months prior to randomization.

2. Have a history of chronic diarrheal disease including inflammatory bowel disease (Crohn's disease or ulcerative colitis).

3. Have had a positive diagnostic test for other GI pathogens, considered to be clinically relevant, within 2 weeks of randomization.

4. Have had major gastrointestinal (GI) surgery (e.g. significant bowel resection) within 3 months of randomization (this does not include appendectomy). The presence of a colostomy or ileostomy or likely requirement of an ostomy during the study.

5. Have life threatening or fulminant CDI with evidence of hypotension, septic shock, peritoneal signs or absence of bowel sounds, or toxic megacolon.

6. History of bone marrow or hematopoietic stem cell transplant at any time or a known current history of a severely compromised/suppressed immune system that, in the opinion of the Investigator, would make the patient unsuitable for the study.

7. Have had more than the equivalent of 24 hours of dosing of antimicrobial treatment active against the current episode of CDI prior to randomization. (i.e. more than four doses of oral vancomycin, two doses of fidaxomicin or three doses of metronidazole).

8. Prior or current use of anti-toxin antibodies including bezlotoxumab within the past 6 months prior to randomization.

9. Are unable to discontinue products used affecting disease progression at randomization.

10. Has been involved in a clinical trial and received an investigational medicinal product for indications other than CDI within 1 month or five half-lives (whichever is longer) or within 3 months if the investigational medical product was for CDI.

11. Have received an investigational vaccine against C. difficile.

12. Patients that the Investigator feels are inappropriate for the study this would include those;

1. with any other condition that, in the Investigator's judgment, would make the patient unsuitable for inclusion in the study.

2. who, in the opinion of the Investigator, are not likely to complete the study for whatever reason, e.g. short life expectancy.

3. with known hypersensitivity or intolerance to ridinilazole, vancomycin, and/or their excipients

4. who are unwilling or unable to comply with protocol requirements, e.g. complete the full course of study treatment per schedule, attend study visits, report diarrhea/suspected recurrence, provide stool samples, ingest capsules/tablets or blood draws.

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

Sponsors

Summit Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lori Styles, MD

Role: STUDY_DIRECTOR

Summit Therapeutics

Locations

University of Alabama - Birmingham

Birmingham, Alabama, United States

GI Alliance - Arizona Digestive Health - Sun City

Sun City, Arizona, United States

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Facey Medical Foundation

Mission Hills, California, United States

Paradigm Clinical Research Centers, Inc

Redding, California, United States

University Of California Davis

Sacramento, California, United States

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Alliance Medical Research LLC

Lighthouse PT, Florida, United States

Phoenix Medical Research LLC

Miami, Florida, United States

San Marcus Research

Miami Lakes, Florida, United States

Gasteroenterology Group of Naples

Naples, Florida, United States

HeuerMD Research Inc

Orlando, Florida, United States

Pines Care Research Center Inc.

Pembroke Pines, Florida, United States

Bardmoor Gastroenterology

Seminole, Florida, United States

Professional Health Care of Pinellas

St. Petersburg, Florida, United States

Florida Medical Clinic P.A.

Zephyrhills, Florida, United States

Infectious Disease Specialists of Atlanta

Decatur, Georgia, United States

Grand Teton Research Group PLLC

Idaho Falls, Idaho, United States

GI Alliance - Illinois Gastro Group - Glenview

Glenview, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

UnityPoint Health Peoria/Proctor

Peoria, Illinois, United States

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Carle Foundation Hospital

Urbana, Illinois, United States

The University of Kansas Medical Center

Kansas City, Kansas, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

University of Maryland School of Medicine

Baltimore, Maryland, United States

St. Vincent Hospital

Worcester, Massachusetts, United States

Harper Hospital Department of Pharmacy Services

Detroit, Michigan, United States

Detroit Receiving Hospital Department of Pharmacy Services

Detroit, Michigan, United States

Aa Mrc Llc

Flint, Michigan, United States

William Beaumont Hospital

Royal Oak, Michigan, United States

Revival Research Institute, LLC.

Southfield, Michigan, United States

Mercury Street Medical Group PLLC

Butte, Montana, United States

AB Clinical Trials

Las Vegas, Nevada, United States

New York Presbyterian Hospital Weill Cornell

New York, New York, United States

James J. Peters VAMC

The Bronx, New York, United States

ECU Adult Specialty Care

Greenville, North Carolina, United States

PMG Research of Winston-Salem

Winston-Salem, North Carolina, United States

St. Vincent Mercy Medical Center

Toledo, Ohio, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Monument Health Clinical Research

Rapid City, South Dakota, United States

Chattanooga Research and Medicine CHARM

Chattanooga, Tennessee, United States

GI Alliance - Texas Digestive Disease Consultants - Arlington

Arlington, Texas, United States

GI Alliance - Texas Digestive Disease Consultants - Cedar Park

Cedar Park, Texas, United States

DM Clinical Research (Conroe Regional Hospital)

Conroe, Texas, United States

FMC Science

Lampasas, Texas, United States

GI Alliance - Texas Digestive Disease Consultants - San Marcos

San Marcos, Texas, United States

GI Alliance - Texas Digestive Disease Consultants - Webster

Webster, Texas, United States

Infectious Diseases Associates of Central VA

Lynchburg, Virginia, United States

Centro Médico Talar

El Talar, Buenos Aires, Argentina

Instituto Medico Platense

Buenos Aires, , Argentina

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

Hospital Ramos Mejía

Buenos Aires, , Argentina

Hospital Privado Centro Medico Cordoba

Córdoba, , Argentina

Instituto Medico ALAS

Salta, , Argentina

Westmead Hospital

Westmead, New South Wales, Australia

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Mater Misericordiae

South Brisbane, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Monash Medical Center

Clayton, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Unidade de Pesquisa - NCS - Hospital Felício Rocho

Belo Horizonte, Minas Gerais, Brazil

Hospital Vera Cruz

Belo Horizonte, Minas Gerais, Brazil

Santa Casa De Misericordia De Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital das Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Ernesto Dornelles

Porto Alegre, Rio Grande do Sul, Brazil

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Hospital Alemao Oswaldo Cruz

São Paulo, , Brazil

MHAT "Sv.Ivan Rilski-2003"OOD

Dupnitsa, Kyustendil, Bulgaria

"MHAT - Blagoevgrad, EOOD Department of Gastroenterology"

Blagoevgrad, , Bulgaria

DCC1-Sliven Ltd.

Sliven, , Bulgaria

DCC Alexandrovska

Sofia, , Bulgaria

Medical center - Izgrev

Sofia, , Bulgaria

Foothills Medical Centre, South Tower

Calgary, Alberta, Canada

Moncton Hospital/Horizon Health Network

Moncton, New Brunswick, Canada

Lakeridge Health

Oshawa, Ontario, Canada

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

Centre integre universitaire de sante et de services sociaux de la Mauricie-et-du-Centre-du-Quebec

Trois-Rivières, Quebec, Canada

Institut Universitaire de Cardiologie et de Pneumologie de Québec- ULaval

Québec, , Canada

Recherche Médicale St-Jérôme Inc

Québec, , Canada

General Hospital of Athens ''Evangelismos'

Athens, , Greece

General Hospital of Athens ''Alexandra''

Athens, , Greece

"Pathophysiology Department Athens University Medical School"

Athens, , Greece

" ATTIKON University Hospital"

Athens, , Greece

"'Hygeia'' Hospital 2nd Department of Medicine and Infectious Diseases"

Athens, , Greece

University Hospital of Heraklion

Heraklion, , Greece

University Hospital of Patras

Pátrai, , Greece

''Tzaneio'' General Hospital of Piraeus

Piraeus, , Greece

Békés Megyei Központi Kórház Pándy Kálmán Tagkórház, Infektológia-Hepatológia Osztály

Gyula, Bekes County, Hungary

Pest Megyei Flór Ferenc Kórház, V. Belgyógyászat

Kistarcsa, Pest County, Hungary

Dr. Kenessey Albert Kórház Rendelőintézet, Tüdőgyógyászati Aktív Osztály

Balassagyarmat, , Hungary

Békés Megyei Központi Kórház Dr. Réthy Pál Tagkórház IV. Belgyógyászat - 2. Gasztroenterológia

Békéscsaba, , Hungary

"Dél-Pesti Centrumkórház-OHII Szent László Kórház Infektológiai Osztály "

Budapest, , Hungary

Országos Korányi Pulmonológiai Intézet, Központi Intenzív osztály

Budapest, , Hungary

CRU Hungary Kft BAZ Megyei Kórház és Egyetemi Oktatókórház, Szent Ferenc Tagkórház

Miskolc, , Hungary

"Pécsi Tudományegyetem I. sz. Belgyógyászat i Klinika, Infektológiai tanszék"

Pécs, , Hungary

Pécsi Tudományegyetem Klinikai Központi Gyógyszertár

Pécs, , Hungary

Csongrad County Dr. Bugyi Istvan Hospital, Dept. Of Internal Medicine

Szentes, , Hungary

Javorszy Odon Hospital

Vác, , Hungary

Waitemata District Health Board WDHB North Shore Hospital

Takapuna, Auckland, New Zealand

Taranaki District Health Board TDHB - Taranaki Base Hospital

New Plymouth, Taranki, New Zealand

Waikato District Health Board Waikato Hospital

Hamilton, Waikato Region, New Zealand

Gabinet Lekarski Bartosz Korczowski

Rzeszów, Podkarpackie Voivodeship, Poland

SP ZOZ w Bochni Szpital Powiatowy im. B. Marty Wieckiej

Bochnia, , Poland

Szpital Bocheński SP ZOZ w Bochni

Bochnia, , Poland

Klinika Chorób Zakaźnych i Hepatologii Wojewódzki Szpital Obserwacyjno-Zakaźny im. Tadeusza Browicza

Bydgoszcz, , Poland

Szpital Specjalistyczny w Chorzowie

Chorzów, , Poland

Szpital Zakonu Bonifratrów

Katowice, , Poland

Specjalistyczne Gabinety Sp z o.o.

Krakow, , Poland

Korczowski Bartosz Gabinet

Rzeszów, , Poland

ENDOSKOPIA Sp. z o.o.

Sopot, , Poland

Centralny Szpital Kliniczny MSWiA Klinika Chorób Wewnętrznych i Gastroenterologii

Warsaw, , Poland

Klinika Chorób Wewnętrznych i Gastroenterologii z Pododdziałem Leczenia Nieswoistych Chorób Zapalnych Jelit Centralny Szpital Kliniczny MSWiA

Warsaw, , Poland

Wojewódzki Szpital Specjalistyczny im. J. Gromkowskiego we Wrocławiu; I Oddział Chorób Zakaźnych

Wroclaw, , Poland

SUUMC-Boli infectioase

Bucharest, , Romania

Clinical Hospital of Infectious and Tropical Diseases "Dr. Victor Babes"

Bucharest, , Romania

S.C. Sana Monitoring Srl

Bucharest, , Romania

Spitalul Clinic de Boli Infectioase si Tropicale

Bucharest, , Romania

Spitalul Minicipal Caracal

Caracal, , Romania

Spitalul Clinic de Boli Infectioase Constanta

Constanța, , Romania

Spitalul Clinic de Boli Infectioase- Sfanta Parascheva

Iași, , Romania

Spitalul Clinic de Boli Infectioase

Iași, , Romania

Spitalul Clinic Judetean de Urgenta Timisoara

Timișoara, , Romania

" State Budgetary Institution of Healthcare "City Clinical Hospital of n.a. V.M.Buyanova" "

Moscow, , Russia

State budget healthcare institution of Novosibirsk region "City clinical hospital #2"

Novosibirsk, , Russia

Hallym University Chuncheon Sacred Heart Hospital

Chuncheon, Gangwon-do, South Korea

Wonju Severance Christian Hospital

Ilsan-dong, Gangwondo, South Korea

Korea University Ansan Hospital

Ansan-si, Gyeonggi-do, South Korea

Hanyang University Guri Hospital

Guri-si, Gyeonggi-do, South Korea

Hanyang University Seoul Hospital

Ansan, Seoul, South Korea

Hallym University Kangnam Sacred Heart Hospital

Anyang-si, Seoul, South Korea

Kyungpook National University Hospital

Daegu, Seoul, South Korea

Yeungnam University Medical Center

Daegu, Seoul, South Korea

Samsung Medical Center

Irwon-dong, Seoul, South Korea

Keimyung University Dongsan Hospital

Daegu, Yeongnam, South Korea

Inje University Seoul Paik Hospital

Junggu, , South Korea

Kangbuk Samsung Hospital

Seoul, , South Korea

Kangdong Sacred Heart Hospital

Seoul, , South Korea

Korea University Guro Hospital

Soeul, , South Korea

Asan Medical Center

Soeul, , South Korea

Hospital Universitario Cruces

Barakaldo, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario Reina Sofía. Hospital Provincial

Córdoba, , Spain

"Hospital Universtiario Donostia "

Donostia / San Sebastian, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

"Hospital Universitario Marqués de Valdecilla "

Santander, , Spain

Hospital Universitario de Balme

Seville, , Spain

Hospital Universitari Sant Joan de Reus

Tarragona, , Spain

Countries

United States; Argentina; Australia; Brazil; Bulgaria; Canada; Greece; Hungary; New Zealand; Poland; Romania; Russia; South Korea; Spain

References

Okhuysen PC, Ramesh MS, Louie T, Kiknadze N, Torre-Cisneros J, de Oliveira CM, Van Steenkiste C, Stychneuskaya A, Garey KW, Garcia-Diaz J, Li J, Duperchy E, Chang BY, Sukbuntherng J, Montoya JG, Styles L, Clow F, James D, Dubberke ER, Wilcox M. A Randomized, Double-Blind, Phase 3 Safety and Efficacy Study of Ridinilazole Versus Vancomycin for Treatment of Clostridioides difficile Infection: Clinical Outcomes With Microbiome and Metabolome Correlates of Response. Clin Infect Dis. 2024 Jun 14;78(6):1462-1472. doi: 10.1093/cid/ciad792.

Reference Type: DERIVED

PMID: 38305378 (View on PubMed)

Carlson TJ, Endres BT, Basseres E, Gonzales-Luna AJ, Garey KW. Ridinilazole for the treatment of Clostridioides difficile infection. Expert Opin Investig Drugs. 2019 Apr;28(4):303-310. doi: 10.1080/13543784.2019.1582640. Epub 2019 Feb 26.

Reference Type: DERIVED

PMID: 30767587 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SMT19969/C004

Identifier Type: -

Identifier Source: org_study_id

NCT03595566

Identifier Type: -

Identifier Source: nct_alias