Clostridium difficile infection (CDI) MedDRA version: 20.0 Level: PT Classification code 10054236 Term: Clostridium difficile infection System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
Summit (Oxford) Limited
Eligibility
Sex/Gender
All
Inclusion 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 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 (see section 10.4), not breastfeeding, and at least one of the following conditions applies: i. Not a woman of childbearing potential (WOCBP) as defined in section 10.4 OR ii. A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 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). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 340 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 340
Exclusion criteria
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) tract surgery (e.g. significant bowel resection or pancreatectomy) within 3 months of randomization (this does not include appendectomy or cholecystectomy); ;. or 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. This number (EC #6) has been intentionally left blank. 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 teicoplanin, or three doses of metronidazole). 8. Prior or current use of anti-toxin antibodies including bezlotoxumab within the 6 months prior to randomization. 9. Are unable to discontinue products affecting bowel movement or disease progression at randomization (see 6.5.1 for a list of potentially confounding medications). 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: a. patients with any other condition that, in the Investigator's judgment, would make the patient unsuitable for inclusion in the study, such as chronic diarrhea, vomiting that cannot be managed with anti-emetics, inability to swallow study medication, or being medically unstable with a critical illness (e.g. requiring vasopressors, intubation, etc.). Investigators are encouraged to contact the medical monitor to discuss individual cases as required. b. patients who, in the opinion of the Investigator, are not likely to complete the study for whatever reason, e.g. short life expectancy less than 100 days. c. patients with known hypersensitivity or intolerance to ridinilazole, vancomycin, and/or their excipients d. patients or their caregivers 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 bowel movements diarrhea and /suspected recurrence, provide stool samples, ingest capsules/tablets or undergo blood draws.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of 10 days dosing with ridinilazole (200 mg bid) with vancomycin (125 mg qid) in the treatment of patients with CDI;Secondary Objective: • To compare the safety and tolerability of 10 days dosing with ridinilazole (200 mg bid) with vancomycin (125 mg qid) in the treatment of patients with CDI • To characterize the systemic exposure of ridinilazole in a subset of patients treated with ridinilazole (200 mg bid) tablets ••To compare the effect of 10 days' dosing with ridinilazole (200 mg bid) and vancomycin (125 mg qid), on the gut bile acid composition of faecal samples and on the gut microbiome diversity at the end of treatment (EOT);Primary end point(s): Sustained Clinical Response (SCR) is defined as Clinical Response and no recurrence of CDI through 30 days post EOT.;Timepoint(s) of evaluation of this end point: Day 40 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Clinical Response • Clinical Cure • Sustained Clinical Response over 60 days – defined as Clinical Response and no recurrence of CDI through 60 days post EOT • Sustained Clinical Response over 90 days – defined as Clinical Response and no recurrence of CDI through 90 days post EOT • Change from baseline to EOT of the relative abundance of the 3 main bile acid groups (conjugated primary, primary and secondary bile acids) • Change from baseline to EOT of the gut microbiota a-diversity (Shannon) index • Change from baseline to EOT of the gut microbiota ß-diversity (Bray- Curtis) index in stool samples;Timepoint(s) of evaluation of this end point: • Clinical Response • Clinical Cure • Sustained Clinical Response over 60 days – defined as Clinical Response and no recurrence of CDI through 60 days post EOT • Sustained Clinical Response over 90 days – defined as Clinical Response and no recurrence of CDI through 90 days post EOT • Change from baseline to EOT of the relative abundance of the 3 main bile acid groups (conjugated primary, primary and secondary bile acids) • Change from baseline to EOT of the gut microbiota a-diversity (Shannon) index • Change from baseline to EOT of the gut microbiota ß-diversity (Bray- Curtis) index in stool samples | — |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Greece, Hungary, Italy, Korea, Republic of, New Zealand, Poland, Romania, Russian Federation, Spain, United States
Contacts
Public ContactClinical Operations
Summit (Oxford) Limited
Outcome results
None listed