None listed
Conditions
Interventions
Ridinilazole
Arm Type of group
Dose 1: Ridinilazole 200mg &
Vancomycin Dummy Placebo Dose
2: Ridinilazole Dummy Placebo &
Vancomycin Dummy Placebo Dose
3: Ridinilazole 200mg & Vancomycin
Dummy Placebo Dose 4: Ridinilazole
Dummy Placebo & Vancomycin
Dummy Placebo Patients will take
one dose (one tablet and one
capsule) four times a day for 10
days (40 doses). It is important that
patients are instructed to complete
the full 10 day course of IMP in
order to fully evaluate effi
Dose 1:Ridinilaz
Sponsors
Summit (Oxford) Limited,
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion Criteria Patients are eligible to be included in the study only if all the following criteria apply: Age 1. Patient must be at least 18 years of age, at the time of signing the informed consent. Type of Patient and Disease Characteristics 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 have been produced within 72 hours prior to randomization. Sex 4. Male or Female Male patients: • A male patient must agree to use contraception as detailed in Appendix 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 Appendix 4), not breastfeeding, and at least one of the following conditions applies: i. Not a woman of childbearing potential (WOCBP) as defined in Appendix 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. Informed Consent 5. Has provided documented signed informed consent and any authorizations required by local law (e.g. Protected Health Information [PHI]).
Exclusion criteria
Exclusion criteria: Exclusion Criteria Patients are excluded from the study if any of the following criteria apply: Medical Conditions 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 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. Have a known current history of significantly compromised immune system e.g. a. HIV positive with a CD4<200 cells/mm3 within 6 months of randomization. b. Severe neutropenia with neutrophil count < 500 cells/mL. c. Are on concurrent immunosuppressive therapy for recent (within previous 6 months) or anticipated solid organ transplant or bone marrow transplant. d. Are on a concurrent chemotherapy, radiotherapy or biologic for active malignancy. Or active malignancy with ablative chemotherapy within the past 3 months or anticipated during the study. Prior/Concomitant Therapy 7. Have had more than 24 hours of dosing, or equivalent (i.e. four doses of oral vancomycin, two doses of fidaxomicin or three doses of metronidazole) of antimicrobial treatment active against the current episode of CDI prior to randomization. 8. Prior or current use of anti-toxin antibodies including bezlotoxumab 9. Are unable to discontinue products used to affect bowel movement or disease progression (see Section 6.5.1 for a list of potentially confounding medications). Prior/Concurrent Clinical Study Experience 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. Other Exclusions 12. Patients that the Investigator feels are inappropriate for the study this would include those; a. with any other condition that, in the Investigator´s judgment, would make the patient unsuitable for inclusion in the study. b. who, in the opinion of the Investigator, are not likely to complete the study for whatever reason. E.g. short life expectancy. c. with known hypersensitivity or intolerance to ridinilazole, vancomycin, and/or their excipients d. who are unwilling or unable to comply with protocol requirements, e.g. complete the full course of study treatment per schedule, attend study visits, complete an electronic diary (or have a caregiver able to complete this on the patient’s behalf), provide stool samples, ingest capsules, blood draws.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Statistical Hypotheses The null (H0) and alternative (H1) hypotheses for the primary endpoint, SCR, can be expressed as: H0: μRID = μVAN H1: μRID ≠ μVAN Where μRID and μVAN are the SCR rates for ridinilazole and vancomycin respectively. The primary endpoint of SCR to 30 days post EOT is the most appropriate measure of efficacy for comparison to vancomycin since it captures both cure of the initial infection and any onset of CDI recurrence. The primary analysis of SCR over 30 days post EOT will be analyzed for the mITT population using the Cochran Mantel Haenszel (CMH) test which will be stratified by age (<65 years of age and ≥65 years of age) and history of recurrent CDI (either none or 1-3 previous occurrences). The treatment difference and 95% confidence interval, based on the stratified Miettinen and Nurminen method, will also be presented. A secondary analysis of SCR over 30 days post EOT will be performed for the PP population using the same method. Measure:Sustained clinical response defined as clinical cure at the Assessment Of Cure (AOC) visit and no recurrence of CDI within 30 days post End Of Treatment (EOT). Timepoints:30 days post EOT | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Primary and secondary endpoints will be evaluated utilising patient reported UBMs via an ediary and, where necessary, free toxin test results and the need for CDI treatment. The null (H0) and alternative (H1) hypotheses for the important secondary endpoint, clinical cure at AOC, can be expressed as: H0: μRID - μVAN ≤ -10% H1: μRID - μVAN > - 10% where μRID and μVAN are the clinical cure rates for ridinilazole and vancomycin respectively. The important secondary endpoint, clinical response at AOC, will be analyzed, for the mITT population. The difference between treatment proportions will be presented together with the 95% confidence interval, based on the stratified Miettinen and Nurminen method. Noninferiority in clinical cure at the AOC visit will be established if the lower limit of the 2-sided 95% confidence interval for the difference between treatment proportions (ridinilazole – vancomycin) is greater than -10%. A secondary analysis of clinical response at AOC will be performed for the PP population using the same method. The same methods of analysis as described for the primary endpoint will also be used to assess SCR over 60 days post EOT and SCR over 90 days post EOT for both the MITT and PP populations. Measure:Important Secondary Endpoint: Clinical cure at the AOC visit. Additional Secondary Endpoints: Sustained clinical response over 60 days – defined as clinical cure at the AOC visit and no recurrence of CDI within 60 days post EOT. Sustained clinical response over 90 days – defined as clinical cure at the AOC visit and no recurrence of CDI within 90 days post EOT | — |
Countries
Belarus, Belgium, Canada, Czech Republic, Estonia, France, Georgia, Germany, Israel, Latvia, Lithuania, Mexico, Peru, Romania, Spain, United States
Contacts
Public ContactXimena Siles Luna
SYNEOS HEALTH PERU S.R.L.
Outcome results
None listed