Methods: Two Phase 2a studies have now been conducted in subjects with functioning ileostomies to allow sampling of their intestinal chyme and support the mechanism of action of SYN-004. In the first study, subjects were administered 1 g of IV ceftriaxone (CRO) alone and in combination with one of two dose strengths of SYN-004. In the second study, CRO plus SYN-004 was administered in the presence or absence of the proton pump inhibitor (PPI), esomeprazole, to determine the effect of pH change on SYN-004 activity. Serial plasma and intestinal chyme samples from each study were analyzed for their concentrations of CRO and SYN-004.
SYN-004 effectively degrades CRO excreted into the small intestine
The plasma PK of CRO is unchanged by oral SYN-004 administration
SYN-004 is not detected in the plasma
The use of proton pump inhibitors does not reduce SYN-004 efficacy
SYN-004 is well tolerated when administered with IV CRO
Of particular importance is that co-administration with a PPI did not impact and may, in some cases, enhance SYN-004’s ability to degrade CRO in the gut. In a hospital clinical setting, this is of importance since many patients are on concomitant PPI therapy.
Conclusion: These two studies support SYN-004’s ability to degrade certain IV beta-lactam ABX in the human intestine and support progression into a currently enrolling Phase 2b clinical trial to examine its capacity to prevent C. difficile-associated disease and antibiotic-associated diarrhea in patients being treated with IV CRO for lower respiratory tract infection.
Synthetic Biologics, Inc.:
E. Sicard, None
M. Rufiange, None
R. Fedorak, None
C. Carter, None
O. Coughlin, Synthetic Biologics, Inc.: Employee , Salary
H. Whalen, Synthetic Biologics, Inc.: Employee , Salary
K. Gottlieb, Synthetic Biologics, Inc.: Employee , Salary
J. Sliman, Synthetic Biologics, Inc.: Employee , Salary