Safety and Efficacy of a Novel Vaginal Anti-infective, TOL-463, in the Treatment of Bacterial Vaginosis and Vulvovaginal Candidiasis: A Randomized, Single-blind, Phase 2, Controlled Trial

Clin Infect Dis. 2019 Feb 15;68(5):803-809. doi: 10.1093/cid/ciy554.


Background: Bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) present serious reproductive health risks and management challenges, with poor control attributed to survival of treatment-resistant biofilm communities. Boric acid is used in various regimens for non-albicans VVC and recurrent BV. We investigated safety and efficacy of a novel boric acid-based vaginal anti-infective with enhanced antibiofilm activity (TOL-463) in treating BV and VVC.

Methods: In this phase 2 randomized, investigator-blinded trial conducted at 2 sexual health clinics, women with BV or VVC were randomly assigned (1:1) to 7 nights of TOL-463 vaginal gel or insert. The primary test of cure (TOC) was clinical cure at day 9-12; safety was assessed at TOC and day 21-30.

Results: One hundred six participants (53 with BV, 36 VVC, 17 both) were enrolled; most were African American (69%). Clinical cure rate of BV at TOC was 59% (95% confidence interval [CI], 41%-75%) for TOL-463 insert and 50% (95% CI, 31%-69%) for TOL-463 gel, and for VVC, 92% (95% CI, 67%-99%) for TOL-463 insert and 81% (95% CI, 57%-93%) for TOL-463 gel. Both products were safe and well tolerated with no secondary cases of VVC; vulvovaginal burning was the most common adverse event (9.6%).

Conclusions: TOL-463, especially in vaginal insert form, is effective and safe in treating BV and VVC. Future studies should assess the potential role of TOL-463 as a biofilm disrupter in enhancing likelihood of cure relative to approved therapies, reducing recurrence rates, and combined with traditional antimicrobials.

Clinical trials registration: NCT02866227.

Keywords: TOL-463; bacterial vaginosis; boric acid; vaginal biofilm; vulvovaginal candidiasis.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Anti-Infective Agents / pharmacology
  • Anti-Infective Agents / therapeutic use*
  • Borates / pharmacology
  • Borates / therapeutic use*
  • Boric Acids / pharmacology
  • Boric Acids / therapeutic use*
  • Candidiasis, Vulvovaginal / drug therapy*
  • Edetic Acid / analogs & derivatives*
  • Edetic Acid / pharmacology
  • Edetic Acid / therapeutic use*
  • Female
  • Humans
  • Middle Aged
  • Vaginosis, Bacterial / drug therapy*
  • Young Adult


  • Anti-Infective Agents
  • Borates
  • Boric Acids
  • TOL-463
  • Edetic Acid

Associated data