BACKGROUND AND PURPOSE:

• Oteseconazole is an oral selective inhibitor of fungal CYP51
• Sobel et al. (NEJM Evidence, 2022) report on two phase 3, randomized placebo-controlled clinical trials of oteseconazole oral capsules in the treatment of RVVC through 48 weeks

METHODS:

• Two global, phase 3, multicenter, randomized, double-blind, placebo-controlled trials
  • VIOLET: CL-011 and CL-012
• Participants
  • Women with ≥3 symptomatic acute vulvovaginal candidiasis (VVC) episodes within the previous 12-month period
  • Acceptable contraception methods required
• Interventions
  • Oteseconazole: 150 mg of oral daily for 7 days and then once weekly for 11 weeks
  • Placebo
• Study design
  • During the screening VVC episode, participants had their VVC cleared with fluconazole induction therapy
  • Participants were then assigned 2:1 to an intervention group at baseline (maintenance phase)
  • Time-to-first-recurrence data collected during the maintenance phase
• Primary outcome
  • Oteseconazole efficacy through week 48
• Secondary outcomes
  • Time to first recurrence
  • Safety
  • Patient-reported outcomes

RESULTS:

• Oteseconazole: 435 | Placebo: 217 (across two trials)
• There were 13 pregnancies
  • Oteseconazole: 8
  • Placebo: 5 
• Average percentage of participants with one or more RVVC episodes through week 48 was significantly lower in the oteseconazole groups vs placebo (P<0.001)
  • CL-011
    • Oteseconazole: 6.7% (range, 6.5 to 7.4)
    • Placebo: 42.8% (range, 41.3 to 45.0)
  • CL-012
    • Oteseconazole: 3.9% (range, 3.7 to 4.6)
    • Placebo: 39.4% (range, 38.0 to 42.6)
• Among those who experienced an RVVC episode, the mean time to recurrence was significantly longer in the oteseconazole groups (P<0.001)
  • CL-011
    • Oteseconazole: 45.7 weeks
    • Placebo: 27.8 weeks
    • Hazard ratio 0.11 (95% CI, 0.06 to 0.21)
  • CL-012
    • Oteseconazole: 47.2 weeks
    • Placebo: 33.1 weeks
    • HR 0.08 (95% CI, 0.04 to 0.17)
• Types and frequencies of treatment related adverse events were similar between groups in both trials
  • No serious treatment related adverse events
  • No adverse effects on
    • Pregnancy outcomes | Liver function | QT interval

CONCLUSION:

• Oral oteseconazole effectively prevented recurrent VVC through 48 weeks
• Adverse events were mostly mild

Learn More – Primary Sources:

Efficacy and Safety of Oteseconazole in Recurrent Vulvovaginal Candidiasis

FDA: HIGHLIGHTS OF PRESCRIBING INFORMATIOn for VIVJOA

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