Phase 3 study findings showed that cadazolid is inferior to vancomycin for treating Clostridioides difficile.
Johnson & Johnson had been developing cadazolid, a novel quinoxolidinone antibiotic, to treat C. difficile, but halted the program last year, presumably based on the results from this trial, Dale N. Gerding, MD, research physician at the Edward Hines Jr. VA Hospital in Hines, Illinois, told Infectious Disease News.
“C. difficile infection is a major global health problem, with the emergence of the 027/BI/NAP1 epidemic strain contributing to morbidity and mortality. Treatments for C. difficile infection are metronidazole, vancomycin, and fidaxomicin; however, for the epidemic strain, high recurrence is associated with all three of these antibiotics,” Gerding and colleagues wrote in The Lancet Infectious Diseases. “A new drug that reduces recurrence or improves outcomes for patients infected with the epidemic strain, or those with severe disease, is an unmet medical need.”
To determine if cadazolid could be an effective alternative, Gerding and colleagues designed two identical, multicenter, double-blind, placebo-controlled, non-inferiority, randomized phase 3 trials called IMPACT 1 and IMPACT 2.
According to the published study, Gerding and colleagues enrolled 1,263 adult patients with mild-to-moderate or severe C. difficile infection between March 28, 2014, and March 24, 2017, for IMPACT 1 and Dec. 13, 2013, and May 2, 2017, for IMPACT 2, and randomly assigned them to receive cadazolid or vancomycin. Participants were given either oral cadazolid 250 mg twice daily with vancomycin-matching placebo capsule four times daily, or oral vancomycin 125 mg four times a day with cadazolid-matching placebo suspension twice daily for 10 days, Gerding and colleagues explained.
According to researchers, cadazolid was safe and well-tolerated by participants. However, it did not achieve the primary goal of noninferiority to vancomycin for clinical cure of C. difficile. Results showed that in the IMPACT 1 modified intention-to-treat population, 84% of participants (253 of 302) experienced clinical cure in the cadazolid group vs. 85% (271 of 318) in the vancomycin group. In IMPACT 2, 81% (235 of 290) vs. 86% (258 of 301) experienced clinical cure. Additionally, in the per-protocol population, 88% (247 of 282) vs. 92% (264 of 288) experienced clinical cure in IMPACT 1 and 87% (214 of 247) vs. 92% (237 of 259) in IMPACT 2. Gerding and colleagues concluded that noninferiority to vancomycin for clinical cure was shown in IMPACT 1 but not in IMPACT 2 and that the safety and tolerability of the two antibiotics were similar.
“Noninferiority of cadazolid to vancomycin was shown in only one of two studies based on the predefined primary endpoint. Sustained cure fractions were not significantly different between cadazolid and vancomycin,” the authors wrote. “Both the sensitivity analysis and the supportive exploratory endpoint of investigators’ assessments of clinical cure suggest noninferiority for cadazolid compared with vancomycin on clinical response. However, as the primary endpoint was not met in these studies, there are no plans to further investigate cadazolid for the treatment of C. difficile infections.” – by Caitlyn Stulpin
Disclosures: Gerding reports numerous ties to industry. Please see the study for all other authors’ relevant financial disclosures.