Clostridium difficile infection MedDRA version: 18.1 Level: PT Classification code 10054236 Term: Clostridium difficile infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: SMT19969
Product Code: SMT19969
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: 2,2'-bis(4-Pyridyl)-3H,3'H-5,5'-bibenzimidazole, t
Sponsors
Summit (Oxford) Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of screening. 1. Willingness to comply with all study activities and procedures and to provide signed, written informed consent prior to any study procedures. If a subject is unable to provide informed consent due to their medical condition, the subject’s legal representative will be provided with study information in order for consent to be obtained. Where required and agreed by the subject a designated family member/next of kin/carer “caregiver” may support an individual in their participation in the study. These individuals must be fully informed of the study requirements and the limits/requirements of their participation. 2. Male or female subjects who are in-patients or out-patients at time of consent, 18 years of age or older, and satisfy the diagnosis of CDI by clinical and laboratory criteria. a. Diarrhoea defined as a change in bowel habits, with >3 unformed bowel movements (UBMs) or >200 mL unformed stool for subjects having rectal collection devices in the 24 hours prior to randomization; b. Presence of either toxin A and/or B of C. difficile in the stool determined by any locally available FDA cleared test (US Only) for C. difficile toxin, including the Alere C.DIFF QUIK CHEK COMPLETE® rapid test, Enzyme Immunoassays (EIA) for C. difficile Toxin (A [TcdA], B [TcdB], or both A and B [TcdA/B]) or Cell Cytotoxicity Neutralization Assay (CCNA) within 72 hours prior to randomization. AND/OR Presence of a toxigenic strain of C. difficile determined by a locally available FDA cleared Nucleic Acid Amplification Test (NAAT) to detect the presence of either toxin genes or the pathogenicity locus (PaLoc) or Non-FDA cleared tests* within 72 hours prior to randomization. 3. No prior antimicrobial treatment > 30 hours for current episode of CDI. 4. Female subjects of childbearing potential and who are sexually active must be using at least two adequate and reliable methods of contraception (e.g., barrier with additional spermicide foam or jelly, intrauterine device, hormonal contraception). Females who are postmenopausal (at least one year without menses) will be considered not of childbearing potential. 5. Subjects (both male and female) must agree to avoid conception during the treatment phase and until the end of their participation in the study 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 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of screening. 1. Life-threatening or fulminant CDI with evidence of hypotension [systolic blood pressure less than 90 mmHg], septic shock, peritoneal signs or ileus, or toxic megacolon. 2. Subjects with history of inflammatory bowel disease (Crohn’s disease or ulcerative colitis). 3. Subjects with 2 or more episodes of CDI in the previous year. 4. Females who are pregnant or breastfeeding. 5. Concurrent use of any product which may have a significant affect upon bowel motility (e.g., metoclopramide, narcotics, loperamide) anti-diarrhoeals, anti-peristalics or any product which may slow bowel movement. Chronic and continued use of such products may be allowed during the study if bowel motility has stablised. 6. Participation in other clinical research studies using an investigational product within one month prior to screening or within 5 half-lives of the investigational agent, whichever is longer 7. Co-administration of potent P-glycoprotein inhibitors such as cyclosporine, ketoconazole, erythromycin, clarithromycin, verapamil, dronedarone and amiodarone. 8. Subjects that the Investigator feels are inappropriate for the study will not be included, e.g. subjects with known hypersensitivity or intolerance to SMT19969, fidaxomicin (and the macrolide antibacterial class of compounds) and their excipients; recent use of pro or prebiotics; prior history of faecal microbiota transplant (FMT) or bowel/stomach surgery
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of 10 days dosing with SMT19969 (200mg BID) compared to fidaxomicin (200mg BID) in the treatment of subjects with CDI; Secondary Objective: • To assess the plasma pharmacokinetics of SMT19969 in patients with CDI. • To assess the qualitative and quantitative effect of SMT19969 and fidaxomicin on the bowel flora of subjects. • To evaluate the efficacy of 10 days dosing with SMT19969 (200mg BID) compared to fidaxomicin (200mg BID) in the treatment of subjects with CDI. • Additional microbiological assessments: C. difficile spore counts and the culture, isolation and quantification of C. difficile. Antibiotic susceptibility testing will be performed on these isolates using a panel to include but not limited to fidaxomicin, vancomycin and metronidazole. C. difficile strains isolated from subjects will undergo characterisation by molecular typing by ribotyping. The presence of vancomycin resistant enterococci (VRE) will be assessed by culture. • To assess the plasma, urine and faecal concentrations of SMT19969 and its metabolites in patients with CDI receiving SMT19969. ;Primary end point(s): Number of AEs and SAEs reported within the study;Timepoint(s) of evaluation of this end point: Monitored throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Monitored throughout the study; Secondary end point(s): • Plasma, urine and faecal concentrations of SMT19969 and its metabolites • The use of 16S ribosomal RNA sequencing, metagenomic and bioinformatic techniques to investigate the bacterial flora of each subject beyond the cultivable species and thus determine deeper effects on bowel flora during therapy. • Investigator assessed clinical response at the Test Of Cure (TOC) visit - with clinical cure defined as the resolution of diarrhoea (= 3 Unformed Bowel Movements (UBMs) per day) while on treatment that is maintained until the TOC visit. • Sustained Clinical Response - defined as clinical cure at TOC and no recurrence of CDI within 30 days post EOT. Recurrence defined as a new episode of diarrhoea between TOC and end of study with a positive C.difficile diagnostic result and the subject requiring antimicrobial treatment active against C. difficile that is started between TOC and End of Study (Day 40). • Time to resolution of diarrhoea (TTROD) • Time to hospital discharge for in-patients • Recurrence rate of CDI | — |
Countries
Czech Republic, United Kingdom
Contacts
Public ContactClinical Operations
Summit (Oxford) Limited
Outcome results
None listed