Phase 3 study evaluating the safety and efficacy of oteseconazole in the treatment of recurrent vulvovaginal candidiasis and acute vulvovaginal candidiasis infections - 02/12/22
Abstract |
Background |
Recurrent vulvovaginal candidiasis affects nearly 138 million women globally each year. In the United States, fluconazole is considered the standard of care for acute vulvovaginal candidiasis, but until recently there was no US Food and Drug Administration–approved drug for the treatment of recurrent vulvovaginal candidiasis. Oteseconazole is a novel oral selective inhibitor of fungal lanosterol demethylase (sterol 14α-demethylase cytochrome P450, an enzyme required for fungal growth) approved for the treatment of recurrent vulvovaginal candidiasis.
Objective |
This study was conducted to evaluate the efficacy and safety of oral oteseconazole (VT-1161) in the prevention of recurrent culture-verified acute vulvovaginal candidiasis episodes through 50 weeks in participants with recurrent vulvovaginal candidiasis and to compare the efficacy of oteseconazole and fluconazole in the treatment of the presenting acute vulvovaginal candidiasis episode.
Study Design |
Women and postmenarcheal girls aged ≥12 years with a history of recurrent vulvovaginal candidiasis (N=219) were enrolled at 38 US sites. Eligible participants presenting with an active vulvovaginal candidiasis infection entered an induction phase in which they were randomly assigned 2:1 to receive 600 mg oral oteseconazole on day 1 and 450 mg on day 2, with matching placebo capsules, or to 3 sequential 150-mg oral doses (once every 72 hours) of fluconazole, with matching placebo capsules. Following the 2-week induction phase, the 185 participants with resolved acute vulvovaginal candidiasis infection (a clinical signs and symptoms score of <3) entered the maintenance phase and received 150 mg of oteseconazole or placebo weekly for 11 weeks. Participants were observed for an additional 37 weeks.
Results |
In the induction phase, oteseconazole was noninferior to fluconazole in the proportion of participants in the intent-to-treat population with resolved acute vulvovaginal candidiasis infection at the week 2 (day 14) test-of-cure visit, with 93.2% of participants on oteseconazole vs 95.8% on fluconazole achieving resolution. In the maintenance phase, oteseconazole was superior to placebo in the proportion of participants in the intent-to-treat population with ≥1 culture-verified acute vulvovaginal candidiasis episode through 50 weeks, 5.1% compared with 42.2%, respectively (P<.001). Overall, treatment-emergent adverse event rates were similar in both groups: 54% for participants who received oteseconazole in the induction and maintenance phases vs 64% for participants who received fluconazole in the induction phase and placebo in the maintenance phase. Most treatment-emergent adverse events in each group were mild or moderate, with 3.4% of treatment-emergent adverse events graded as severe or higher in the OTESECONAZOLE/oteseconazole group vs 4.2% in FLUCONAZOLE/placebo group.
Conclusion |
In participants with recurrent vulvovaginal candidiasis, oteseconazole was safe and efficacious in the treatment and prevention of recurrent acute vulvovaginal candidiasis episodes and was noninferior to vulvovaginal candidiasis standard-of-care fluconazole in the treatment of the presenting acute vulvovaginal candidiasis infection.
Le texte complet de cet article est disponible en PDF.Key words : antifungal, induction therapy, maintenance therapy, oteseconazole, VT-1161, prophylaxis, RVVC, recurrent vulvovaginal candidiasis, yeast infection
Plan
| M.G.M. and B.M. share first authorship. |
|
| S.R.B., T.D., K.P., and S.C. are employees of Mycovia Pharmaceuticals, Inc. (Mycovia). The study reported in this article was sponsored by Mycovia. Oteseconazole is under development by Mycovia for the treatment of recurrent vulvovaginal candidiasis. M.G.M. participated as a principal investigator of the ultraVIOLET Study and has received research funding for this study through his healthcare organization. B.M. participated as a principal investigator and is also a consultant for and/or has received research funding from Mycovia. Furthermore, he is a consultant and speaker for Sage Therapeutics and Evofem Biosciences. M.G. acted as central laboratory for this trial. A.F. analyzed the data for this trial and is a statistics consultant for Mycovia. |
|
| This study was registered on ClinicalTrials.gov (clinicaltrials.gov identifier NCT03840616; NCT03840616). The date of registration was February 15, 2019, and the date of initial participant enrollment was March 13, 2019. |
|
| Mycovia is committed to facilitating advances in the prevention, diagnosis, and treatment of disease. This commitment involves the public disclosure of clinical trial results to study participants, as well as physicians and other members of the scientific community. The study participants have consented to the use of pseudonymized individual results for research purposes, and all documentation of study tests and procedures is accessible to participants in individual medical records kept at study sites. All Mycovia-supported research is intended to contribute to the broad scientific and medical body of knowledge, and results will be published in accordance with Mycovia policies. The study sites and investigators have been granted certain publication rights regarding site-level data and activities through contractual arrangements with Mycovia. Through its process related to investigator-initiated studies, Mycovia will individually consider additional requests for disclosure of consolidated clinical trial data. Academic investigators and other researchers may submit concept proposals and study protocols for retrospective data review by email to grants@mycovia.com. Data requested for bona fide research purposes shall be provided with the understanding that researchers and physicians retain and exercise independent professional and scientific judgment in any evaluation. The collection and management of protected personal and health data are governed by applicable law; the Mycovia Privacy Policy is located at the following web address: privacy. |
|
| The summary findings of this study were presented at the 10th Anniversary IDWeek Meeting, a joint annual meeting of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medical Association, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists; virtual conference, September 29, 2021, to October 3, 2021, and the 4th Annual International Society for Infectious Diseases in Obstetrics and Gynaecology Congress 2021, the Hungarian Society for Obstetrics and Gynecology, hybrid virtual conference and in Budapest, Hungary, October 14–17, 2021. |
|
| Cite this article as: Martens MG, Maximos B, Degenhardt T, et al. Phase 3 study evaluating the safety and efficacy of oteseconazole in the treatment of recurrent vulvovaginal candidiasis and acute vulvovaginal candidiasis infections. Am J Obstet Gynecol 2022;227:880.e1-11. |
Vol 227 - N° 6
P. 880.e1-880.e11 - décembre 2022 Retour au numéro
Article précédent
- The impact of insurance mandates on donor oocyte utilization: an analysis of 39,338 donor oocyte cycles from the Society for Assisted Reproductive Technology registry
- Jenny S. George, Malinda S. Lee, Rachel K. Ashby, Randi Goldman, Elizabeth S. Ginsburg, Andrea Lanes, Serene S. Srouji
- Age-specific random day serum antimüllerian hormone reference values for women of reproductive age in the general population: a large Chinese nationwide population-based survey
- Yongxiu Hao, Rui Yang, Jia Li, Zehong Zhou, Weiping Qian, Jian Zhang, Ze Wu, Lei Jin, Xueqing Wu, Cuilian Zhang, Beihong Zheng, Jichun Tan, Guimin Hao, Shangwei Li, Qin Li, Danni Zheng, Yuanyuan Wang, Rong Li, Ping Liu, Jie Qiao
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?