Prevention of Clostridium difficile infection (CDI), Clostridium difficile associated diarrhea (CDAD), antibiotic-associated diarrhea (AAD) and secondary infections with healthcare-acquired drug-resistant pathogens in patients receiving IV ß-lactam antibiotic therapy. MedDRA version: 19.0 Level: LLT Classification code 10006834 Term: C.difficile diarrhea System Organ Class: 100000004862
Conditions
Interventions
Product Name: SYN-004 75mg
Product Code: SYN-004
Pharmaceutical Form: Capsule
INN or Proposed INN: Kymerase
CAS Number: 1792207-66-9
Current Sponsor code: SYN-004
Other descriptive name: beta-Lactamas
Sponsors
Synthetic Biologics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients age =50 years 2. Informed consent (IC) obtained and signed prior to study participation 3. Expected minimum hospital stay of 5 days 4. Expected =5 day course of intravenous (IV) ceftriaxone alone or in combination with a macrolide, e.g., clarithromycin or azithromycin 5. Clinical diagnosis of moderate to severe lower respiratory tract infection consisting of signs and symptoms of a lower respiratory tract infection and Pneumonia Severity Index (PSI/PORT) score for CAP of 90-130, inclusive. Evidence of a new or progressive infiltrate on chest x-ray is recommended. Note: the PSI/PORT score inclusion requirement applies to all patients. 6. Patients must agree to use an acceptable method of contraception from the time of signing the ICF to 24 hours after the final dose of study drug if the patient is a sexually active female of child bearing potential (defined as all females after puberty who are not postmenopausal for at least 1 year, or surgically sterile). Adequate contraceptive measures include: oral contraceptives (stable use for 2 or more cycles before Screening); intrauterine device; Depo Provera; Norplant System implants; bilateral tubal ligation; partner with a vasectomy; use of a condom or diaphragm plus either contraceptive sponge, foam, or jelly; and abstinence. 7. Patients must have a negative urine pregnancy test at Day 1 before dosing if a female patient of child bearing potential. 8. The patient is willing and able to comply with all testing and study requirements as defined in the protocol. 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 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 297
Exclusion criteria
Exclusion criteria: 1. Presence of a diarrheal illness within 72 hours prior to randomization 2. Current treatment for CDAD or ongoing active CDAD infection, as evidenced by clinical signs of diarrhea along with the presence of toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool 3. Number of previous CDAD episodes >1 within 12 weeks prior to randomization or CDAD within 4 weeks prior randomization 4. Use of antibiotics within 1 month of start of study drug except for the current illness. Note: Oral antibiotics for the current episode of lower respiratory tract infection within 72 h prior to the first dose of study drug are allowed 5. In the judgment of the investigator any factors (e.g., other treatment) that could invalidate the treatment result 6. Known intolerance of study drug/ingredients 7. Present or past diagnosis of inflammatory bowel disease such as Crohn's Disease or ulcerative colitis. Evidence of active GI infections e.g., parasitic infection, Salmonella, Shigella 8. Patients requiring tracheal intubatation and mechanical ventilation. Non-invasive ventilation including biphasic intermittent positive airway pressure (BiPAP) and continuous positive airway pressure (CPAP) are acceptable 9. Patients with bronchiectasis, cystic fibrosis, aspiration pneumonia, confirmed influenza, or chronic alcoholism 10. Neutrophil count 5x upper limit normal (ULN) 12. Active chemotherapy, receipt of organ transplant 13. Renal failure requiring dialysis 14. Patient is currently enrolled in another clinical study or has received an investigational drug or device within 30 days or within a time period consistent with a washout period of 5 half-lives before signing the ICF, whichever is longer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effectiveness of treatment with SYN-004 for the prevention of Clostridium difficile (C. difficile) associated diarrhea (CDAD) in patients hospitalized for a lower respiratory tract infection receiving intravenous (IV) ceftriaxone alone or in combination with a macrolide. To evaluate the safety and tolerability of SYN-004 in patients with a lower respiratory tract infection receiving IV ceftriaxone alone or in combination with a macrolide.;Secondary Objective: To assess the effectiveness of treatment with SYN-004 for the prevention of antibiotic associated diarrhea (AAD) in patients hospitalized for a lower respiratory tract infection receiving IV ceftriaxone alone or in combination with a macrolide.;Primary end point(s): Percentage of patients with CDAD based on the protocol definition of CDAD from Day 1 to the 4-week Follow-Up Visit in the SYN-004 treatment group compared to the placebo group;Timepoint(s) of evaluation of this end point: 4-week Follow-Up Visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Percentage of patients with CDAD based on the protocol definition of CDAD from Day 1 to the 2-week Follow-Up Visit and 6-week Follow-Up Visit in the SYN-004 treatment group compared to the placebo group - Percentage of patients treated for CDAD from Day 1 to the 4-week Follow-Up Visit and from Day 1 to the 6-week Follow-Up Visit in the SYN-004 treatment group compared to the placebo group - Percentage of patients with AAD based on the protocol definition of AAD from Day 1 to the 2-, 4- and 6-week Follow-Up Visit in the SYN-004 treatment group compared to the placebo group -Percentage of patients treated for AAD from Day 1 to the 4-week Follow-Up Visit and from Day 1 to the 6-week Follow-Up Visit in the SYN-004 treatment group compared to the placebo group. - Percentage of patients with diarrhea based on the protocol definition of diarrhea (3 or more unformed/liquid stools per 24 hour period) from Day 1 to the 2-, 4-, and 6-week Follow-up Visits in the SYN-004 treatment group compared to the placebo group. - Percentage of patients with CDAD or AAD based on the protocol definition of CDAD or AAD from Day 1 to the Day 1 to the 2-, 4- and 6-week Follow-Up Visit in the SYN-004 treatment group compared to the placebo group - Percentage of patients with CDAD or AAD or new colonization with both C. difficile and VRE without diarrhea from Day 1 to the 2-, 4- and 6 week-Follow-Up Visit in the SYN-004 treatment group compared to the placebo group. New colonization is defined as a patient who has a negative screening colonization sample for C. difficile and VRE, and a subsequent positive sample result for both species in the same sample at Treatment Period 2 – 72 Hour Visit or 4-week Follow-Up Visit or Early Termination. - Percentage of patients with new colonization with both C .difficile and VRE without diarrhea from Day 1 to the 2-, 4- and 6-week Follow-Up Visit in the SYN-004 treatment group compared to the placebo group;Timepoint(s) of eval | — |
Countries
Bulgaria, Canada, Hungary, Poland, Romania, Serbia, United States
Contacts
Public ContactTracey Roberts
Synthetic Biologics, Inc.
Outcome results
None listed