An investigational oral antibiotic called zoliflodacin was well-tolerated and successfully cured most cases of uncomplicated gonorrhea when tested in Phase 2 multicenter clinical trial, according to findings published in the  New England Journal of Medicine. The National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health, sponsored the clinical study.

Gonorrhea is caused by the bacterium  Nesseria gonorrhoeae , which has progressively developed resistance to each of the antimicrobials used to treat it. As a result, in 2015, the US Centers for Disease Control and Prevention revised gonorrhea treatment guidelines to recommend dual therapy with injectable ceftriaxone and oral azithromycin to reduce the emergence of resistance to ceftriaxone.

Zoliflodacin

Zoliflodacin (formerly known as ETX0914 and AZD0914), developed by Entasis Therapeutics based in Waltham, Mass., Represents a new type of oral antibiotic that inhibits DNA synthesis in a different way than currently approved antibiotics.

"The rate of reported gonorrhea cases in the United States has increased 75% since 2009, and antibiotic resistance has significantly reduced the number of treatment options for this disease," said Anthony S. Fauci. "These encouraging research findings published today suggest that zoliflodacin has the potential to be useful and easy-to-administer oral antibiotic for treating gonorrhea." Zoliflodacin has the potential to be a useful and easy-to-administer oral antibiotic for treating gonorrhea. "

The study took place from November 2014 through December 2015 and was led by Stephanie N. Taylor, MD, of Louisiana State University Health Sciences Center in New Orleans. Study investigators recruited patients from sexual health clinics there and in Seattle; Indianapolis, Indiana; Birmingham, Alabama; and Durham, NC The trial enrolled 179 participants ages 18 to 55 years with either symptom of uncomplicated urogenital gonorrhea, untreated urogenital gonorrhea or sexual contact with someone with gonorrhea within 14 days before enrollment.

Participants were randomly selected to receive either a single 2 or 3-gram dose of oral zoliflodacin or a 500-milligram (mg) dose of injectable ceftriaxone. Among the 117 per-protocol participants who were evaluated six days after treatment, zoliflodacin or a 500-milligram (mg) dose of injectable ceftriaxone.

Among the 117 per-protocol participants who were evaluated six days after treatment, 98% of those who received the 2-gram zoliflodacin dose, 100% of those who received the 3-gram dose, and all (21 of 21) of the participants in the ceftriaxone group were considered cured of their urogenital gonorrhea based on culture results.

Rectal gonorrheal infections

Zoliflodacin cured all rectal gonorrheal infections (4 of 4 participants who received the 2-gram dose and 6 of 6 participants who received the 3-gram dose) as did ceftriaxone (3 of 3 participants). However, the investigative drug did not affect the patients with the infections of the throat (pharyngeal): 67 percent of volunteers who received the 2- gram dose (4 of 6 participants) and 78% of those who received the 3- gram dose were cured. All of the participants (4 of 4) in the ceftriaxone group achieved a cure.

The investigational antibiotic was well tolerated with transient gastrointestinal upset the most commonly reported adverse effect. Microbiological evaluation of post-treatment clinical isolates did not demonstrate resistance to zoliflodacin.zoliflodacin.

Phase 2 clinical trial formulation

In March 2018, NIAID completed a study to evaluate the pharmacokinetics, safety and tolerability as a single oral dose to serve as a bridge from the Phase 2 clinical trial formulation to the final formulation for Phase 3 testing. Results from that study have not yet been made public.

Additionally, in September 2018 NIAID launched a Phase 1 study to evaluate the drug's cardiac effects, a standard safety test for new drugs such as this.zoliflodacin's pharmacokinetics, safety and tolerability as a single oral dose to serve as a bridge from the Phase 2 clinical trial formulation to the final formulation for Phase 3 testing.

Results from that study have not yet been made public. Additionally, in September 2018 NIAID launched a Phase 1 study to evaluate the drug's cardiac effects, a standard safety test for new drugs such as this.

Zoliflodacin has been awarded fast-track status by the US Food and Drug Administration for development as oral treatment for gonococcal infections. It is expected to begin Phase 3 testing in the Netherlands, South Africa, Thailand and the United States next year.