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
Open accessAbstract
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.
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In a 2019 study of 106 women, TOL-463 cured 92% of VVC patients with the insert and 81% with the gel.
“The percentage of VVC patients cured with the insert was 92%, and the percentage of VVC patients cured with the gel was 81%.”
From Treatment of Vulvovaginal Candidiasis—An Overview of Guidelines and the Latest Treatment Methods (2023) · cites this paper as [41]
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- Authors
- Marrazzo, J. M., Dombrowski, J. C., Wierzbicki, M. R., Perlowski, C., Pontius, A., Dithmer, D., & Schwebke, J.
- Affiliations
- University of Alabama at Birmingham (US)
- University of Washington (US)
- Emmes (United States) (US)
- Family Health International 360 (US)
- Corresponding author
- Marrazzo, Jeanne M
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-08-31
- Volume
- 68
- Issue
- 5
- Pages
- 803-809
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC6376090
- OpenAlex
- W2889350775
- Cited by
- 89
- References
- 0
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 9 · 2023: 18 · 2022: 16 · 2021: 15 · 2020: 8 · 2019: 6 · 2018: 2 · 2012: 1
- FWCI
- 6.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Infectious Diseases (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Health Sciences › Medicine › Epidemiology › Urinary Tract Infections Management
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- boric acid, bacterial vaginosis, vaginal candidiasis, vaginal insert, vaginal gel, antibiofilm activity, biofilm eradication, treatment-resistant infection, cure rate, safety and tolerability
- MeSH terms
- Adolescent, Adult, Anti-Infective Agents, Borates, Boric Acids, Candidiasis, Vulvovaginal, Edetic Acid, Female, Humans, Middle Aged, Vaginosis, Bacterial, Young Adult
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