Although acute vulvovaginal candidiasis (VVC) is common in women, current azole antifungal therapies are frequently linked to safety and resistance concerns. The oral drug VT-1161 (oteseconazole) has a higher selectivity for fungus CYP51. Researchers compared the efficacy and safety of VT-1161 vs. fluconazole in people with moderate to severe acute VVC in this phase 2 clinical trial. Participants with an acute episode of VVC (n=55) were randomly assigned to receive VT-1161 300 mg once daily (q.d. ), 600 mg q.d., or 600 mg twice daily (b.i.d.) for 3 days or a single dose of fluconazole 150 mg (FDA-approved dose to treat acute VVC). The participants were monitored for a period of 6 months. The primary outcome was the proportion of patients with therapeutic (clinical and mycological) cures at day 28. The VT-1161 300 mg q.d. (75.0%), VT-1161 600 mg q.d. (85.7%), and VT-1161 600 mg b.i.d. (78.6%) groups experienced therapeutic cure at a higher rate than the fluconazole group (62.5%) in the per-protocol population; however, the differences were not statistically significant. At 3 and 6 months, no patients in the VT-1161 group had signs of mycological recurrence, compared to 28.5% and 46.1% in the fluconazole group, respectively. No significant adverse events or treatment-emergent adverse events caused the patient to stop taking the medication. On day 28, the majority of patients in all therapy groups had attained therapeutic cure. Through 6 months of follow-up, VT-1161 was well tolerated at all dose levels.