Zoliflodacin Phase 3 Trial Meets Noninferiority Benchmark

Key Takeaways

• A multinational phase 3 non-inferiority trial compared single-dose oral zoliflodacin with ceftriaxone plus azithromycin for uncomplicated urogenital gonorrhea.
• Microbiological cure at test of cure in the microbiological intention-to-treat population met the prespecified non-inferiority benchmark.
• Adverse events were reported as generally similar between groups and mostly mild or moderate.

In this multinational, randomized, controlled, open-label, non-inferiority trial, eligible participants were aged 12 years and older with suspected uncomplicated urogenital gonorrhea. The trial was conducted across 17 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the US.

Participants were randomized 2:1 to receive zoliflodacin 3 g orally or ceftriaxone 500 mg intramuscularly plus azithromycin 1 g orally. The primary endpoint was microbiological cure, defined as eradication of Neisseria gonorrhoeae on urethral or endocervical culture, assessed at test of cure on day 6 ± 2. The primary efficacy analysis used the microbiological intention-to-treat population. Non-inferiority required the upper bound of the two-sided 95% confidence interval for the treatment difference (comparator minus zoliflodacin) to remain below 12%.

Microbiological cure was reported in 460 of 506 participants (90.9%) in the zoliflodacin group and in 229 of 238 (96.2%) in the comparator group. The estimated between-group difference was 5.3%, with a 95% confidence interval of 1.4% to 8.6%. Investigators reported that the upper confidence limit stayed within the prespecified non-inferiority margin, meeting the trial’s non-inferiority benchmark.

Overall safety was described as similar between groups, with most treatment-emergent adverse events characterized as mild or moderate and no serious adverse events reported. With zoliflodacin, the most frequently reported events were headache, neutropenia, and leukopenia. With ceftriaxone plus azithromycin, the most frequent events were injection-site pain, neutropenia, and diarrhea. Zoliflodacin was described as generally well tolerated.