Clinical stage biopharmaceutical company Acurx Pharmaceuticals has completed the Phase I trial of ACX-362E for the treatment of clostridioides difficile infection (CDI). The double-blind, placebo-controlled, multiple-ascending dose trial involved 68 subjects.
It demonstrated the first evidence of human safety in multiple ascending doses of antibiotics that inhibit DNA synthesis in certain bacterial cells, known as pol IIIC inhibitors.
During the trial, multiple dose levels up to 450mg BID for ten days were positively tolerated and no adverse events attributed to ACX-362E were reported.
Blood levels of ACX-362E showed low systemic exposure, indicating poor oral absorption in treating CDI.
Faecal concentrations of ACX-362E at higher dose levels also exceeded the concentrations known to inhibit clostridioides difficile by several hundred-fold and were sustained during the ten-day treatment course.
Acurx co-founder and managing partner Robert DeLuccia said: “The safety, faecal concentration, low systemic exposure and, most importantly, the minimal impact on the healthy gut microbiome provide data to guide selection of our Phase II dose and improve the probability of success and timeline efficiency of our Phase II clinical trial programme.”
ACX-362E is an oral antibacterial agent used for the treatment of CDI, an acute, life-threatening, intestinal infection.
The trial included a six-subject vancomycin treatment arm for comparative microbiome.
The effects of ACX-362E on the faecal microbiome were compared to those produced by vancomycin over the ten-day treatment period.
Vancomycin treatment resulted in a 3-4 log reduction in Bacteroides, while ACX-362E 300mg or 450mg BID doses showed less effect.
Acurx also partnered with Dr Kevin Garey’s laboratory at the University of Houston to conduct microbiome testing of gastrointestinal flora in trial subjects.
Garey said: “The minimal disruption to the healthy gut microbiome identified in this Phase I study population should offer advantages over other therapeutic options for an initial episode of CDI if these salutary effects on the gut microbiome translate into the clinical benefit of reducing recurrent infection.”