Safety, Tolerability and the Pharmacokinetics of Ridinilazole in Adolescent Subjects

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Study to evaluate the safety of ridinilazole in adolescent subjects and how ridinilazole is metabolized.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Summit Therapeutics
• Collaborator: Department of Health and Human Services
• Treatments: Vancomycin

Criteria

Inclusion Criteria:

• Has signed informed consent by parents or legally authorized representatives and assent by the child according to local requirements (e.g., Protected Health Information [PHI]) prior to initiation of any study-mandated procedure.

• Is aged 12 to <18 years.

• Has 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, see Appendix 5)) in the 24 h prior to randomization.

• Has tested positive for 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.

• Has a negative stool test for other pathogens than C. difficile, or a positive test that in the investigator's judgement is not associated with clinically significant signs and symptoms of GI infection, within 48 hours of randomization. Example pathogens may be norovirus, enteroviruses (coxsackie and ECHO), enteric adenoviruses, Salmonella, Shigella, Yersinia and Campylobacter).

• Has contraceptive measures in place as follows (see Appendix 4 for details): Male subject: Agrees to use a highly effective contraceptive method 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 OR Agrees to adhere to abstinence, Refrains from donating sperm during the treatment period and for at least 30 days after the last dose of study treatment. Female subject: Is not pregnant or breastfeeding and must have a documented negative pregnancy test at screening, complies with one of the following three conditions: Not a woman of childbearing potential (WOCBP) as defined in Appendix 4, A WOCBP who agrees to follow the guidance in Appendix 4 on highly effective contraceptive methods during the treatment period and for at least 30 days after the last dose of study treatment, A WOCBP adhering to abstinence.

Exclusion Criteria:

• Has 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).

• Has prior or current use or application of ridinilazole any time in the past, a (investigational) vaccine against C. difficile any time in the past, anti-toxin antibodies including bezlotoxumab within the past 6 months, intravenous immunoglobulin (IVIG) within the past 3 months, fecal microbiota replacement therapy within the past 3 months, or any investigational medicinal product for treatment of CDI within the past 3 months.

• Has life-threatening or fulminant CDI with evidence of hypotension, septic shock, peritoneal signs or absence of bowel sounds, toxic megacolon, or ileus.

• Has had major GI surgery (e.g. significant bowel resection, but not including appendectomy) within the past 3 months or has the presence of a colostomy or ileostomy or has the likely requirement of an ostomy during the study.

• Has current or planned (for within the study period up to Day 40) cancer treatment (including chemotherapy, radiotherapy, biologic treatment (e.g. monoclonal antibodies), immune-oncological treatments) that generally is associated with or currently is causing vomiting and/or severe nausea that cannot be managed with antiemetics and is limiting the ability to take oral medications.

• Has been involved in a clinical trial and received an investigational medicinal product for an indication other than CDI within the past month or five half-lives (whichever is longer).

• Has a known history of bone marrow or hematopoietic stem cell transplantation.

• Is unable to tolerate oral medications

• Has a known history of hypersensitivity or allergic reaction to vancomycin or any excipient of vancomycin or ridinilazole.

• Is, in the Investigator's judgment, inappropriate for participation in the study including for example those subjects with any other (medical) condition that would make the subject unsuitable for inclusion in the study, who are not likely to complete the whole study for whatever reason, e.g., a short life expectancy, or who are unwilling or unable to comply with protocol requirements, for example complete the full course of study treatment, attend study clinic visits, provide stool samples, ingest capsules, tolerate blood draws.