Ibrexafungerp Versus Placebo for Vulvovaginal Candidiasis Treatment: A Phase 3, Randomized, Controlled Superiority Trial (VANISH 303).

BACKGROUND: Current treatment of vulvovaginal candidiasis (VVC) is largely limited to azole therapy. Ibrexafungerp is a first-in-class triterpenoid antifungal with broad-spectrum anti-Candida fungicidal activity. The objective of this study was to evaluate the efficacy and safety of ibrexafungerp compared with placebo in patients with acute VVC. METHODS: Patients were randomly assigned 2:1 to receive ibrexafungerp (300 mg twice for 1 day) or placebo. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms [VSS] = 0) at test-of-cure (day 11 ± 3). Secondary endpoints included the percentage of patients with mycological eradication, overall success (clinical cure and mycological eradication), clinical improvement (VSS ≤ 1) at test-of-cure, and symptom resolution at follow-up (day 25 ± 4). RESULTS: Patients receiving ibrexafungerp had significantly higher rates of clinical cure (50.5% [95/188] vs 28.6% [28/98]; P = .001), mycological eradication (49.5% [93/188] vs 19.4% [19/98]; P < .001), and overall success (36.0% [64/178] vs 12.6% [12/95]; P < .001) compared with placebo. Symptom resolution was sustained and further increased with ibrexafungerp compared with placebo (59.6% [112/188] vs 44.9% [44/98]; P = .009) at follow-up. Post hoc analysis showed similar rates of clinical cure and clinical improvement at test-of-cure for Black patients (54.8% [40/73] and 63.4% [47/73], respectively) and patients with a body mass index >35 (54.5% [24/44] and 68.2% [30/44], respectively) compared with overall rates. Ibrexafungerp was well tolerated. Adverse events were primarily gastrointestinal and mild in severity. CONCLUSIONS: Ibrexafungerp provides a promising safe and efficacious oral treatment that mechanistically differs from current azole treatment options for acute VVC.

EVO100 prevents chlamydia and gonorrhea in women at high risk of infection.

BACKGROUND: According to the Centers for Disease Control and Prevention, rates of infection for Chlamydia trachomatis and Neisseria gonorrhoeae are increasing in the United States. EVO100 is an investigational antimicrobial, pH-modulating, vaginal gel with active ingredients L-lactic acid, citric acid, and potassium bitartrate that is being evaluated for the prevention of sexually transmitted infections. OBJECTIVE: The objective of this phase 2B/3 study was to assess the efficacy and safety of EVO100 for the prevention of chlamydia and gonorrhea. STUDY DESIGN: AMPREVENCE was a double-blinded, placebo-controlled, multicenter study based in the United States conducted over approximately 16 weeks in women at the age of 18 to 45 years who were at risk of urogenital chlamydia and gonorrhea infection. Enrolled women had been diagnosed as having and treated for chlamydia or gonorrhea ≤16 weeks before enrollment. Women received either EVO100 or placebo vaginal gel and were instructed to apply the study drug immediately before or up to 1 hour before each act of vaginal sexual intercourse. The primary and secondary endpoints were the prevention of urogenital chlamydia and gonorrhea, respectively. Exploratory outcomes include women's overall satisfaction with EVO100. RESULTS: In total, 860 women were randomized 1:1 to receive EVO100 (n=426) or placebo (n=434), and 764 women (EVO100, n=376; placebo, n=388) were documented as using the study drug at least once. Baseline characteristics were similar between treatment arms. Overall, women had a mean age of 27.7 years (standard deviation, 6.9) and body mass index of 28.9 kg/m2 (standard deviation, 8.0). Most women were of White (54.3% [467 of 860]) or African American (41.6% [358 of 860]) race and of non-Hispanic/Latina ethnicity (67.1% [577 of 860]). The chlamydia infection rate in EVO100 users was 4.8% (14 of 289) compared with 9.7% (28 of 290) among placebo users (P=.0256), representing a relative risk reduction of 50%. For gonorrhea, the infection rate was 0.7% (2 of 280) in the EVO100 arm compared with 3.2% (9 of 277) in the placebo arm (P=.0316), representing a relative risk reduction of 78%. Increased efficacy was observed with increased adherence, and chlamydia infection rates were significantly reduced with increased adherence in the EVO100 group compared with placebo. Across both arms, there were similar rates of all-cause adverse events (EVO100, 21.3% [80 of 376]; placebo, 20.4% [79 of 388]) and treatment-related adverse events (EVO100, 7.2% [27 of 376]; placebo, 7.5% [29 of 388]). The most common adverse events in the EVO100 arm were vulvovaginal candidiasis (5.1% [19 of 376]), vaginal discharge (3.2% [12 of 376]), and urinary tract infection (3.2% [12 of 376]) and, in the placebo arm, bacterial vaginosis (4.6% [18 of 388]), urinary tract infection (2.6% [10 of 388]), and vaginal discharge (2.6% [10 of 388]). Few women discontinued owing to adverse events in either arm (EVO100, 1.1% [4 of 376]; placebo, 1.5% [6 of 388]). No treatment-related serious adverse events were reported. Most EVO100 users (88%) were satisfied or very satisfied with EVO100 after 16 weeks of use. CONCLUSION: EVO100 significantly reduced the risk of chlamydia and gonorrhea infections in women at high risk of Chlamydia trachomatis and Neisseria gonorrhoeae infection and was well tolerated, with observed adverse events consistent with its known safety profile.

Mechanisms of action of currently available woman-controlled, vaginally administered, non-hormonal contraceptive products.

Woman-controlled, vaginally administered contraceptives offer women discreet, self-administered, and reversible options. This brief report summarizes the mechanisms of action (MOAs) of currently available, woman-controlled, vaginally administered, non-hormonal products, excluding those that need to be fitted by a healthcare provider. MOAs of three general types of contraceptives will be reviewed, including pH modulators, spermicides, and barrier methods. The recently approved vaginal pH modulator (lactic acid, citric acid, and potassium bitartrate) has a non-hormonal MOA, acting as a buffering agent in the presence of alkaline semen and resulting in sperm immobilization. In contrast, spermicides, such as nonoxynol-9, act by lysing sperm membranes, resulting in sperm death. Barrier methods, such as the diaphragm and female condom, prevent sperm from entering the uterus. In addition to their varying MOAs, each woman-controlled, vaginally administered method has different instructions for use, efficacy, side effects, and availability/insurance coverage, thus providing a range of characteristics to fit different needs and preferences.

A novel vaginal pH regulator: results from the phase 3 AMPOWER contraception clinical trial.

OBJECTIVE: The objective was to evaluate the contraceptive effectiveness, safety, and acceptability of a novel vaginal pH regulator over seven cycles of use. STUDY DESIGN: A single-arm, open-label, phase 3 study was conducted across 112 sites in the United States in sexually active 18-35-year-old women at risk of pregnancy. Women administered the study treatment ≤ 1 h before each episode of intercourse. Women recorded use of study drug, coital information, and any symptoms experienced in electronic diaries. The primary outcome was the seven-cycle cumulative pregnancy rate as calculated using the Kaplan-Meier methodology; secondary outcomes included safety. Overall satisfaction was assessed via written questionnaires. RESULTS: A total of 1384 women were enrolled in the study from July 2017 to November 2018. Mean age was 27.7 ±â€¯4.4 years; most women were white (69.0%). The seven-cycle cumulative pregnancy percentage was 13.7% [95% confidence interval (CI): 10.0%-17.5%], meeting the prespecified primary endpoint of having the upper bound 95% CI ≤ 21%. Most common adverse events (AEs) occurring in ≥ 2% of women were vulvovaginal burning sensation, vulvovaginal pruritus, urinary tract infection, vulvovaginal pain, mycotic infection, bacterial vaginosis, and nasopharyngitis. Of 1330 women who used the study drug at least once, fewer than 2% of women discontinued due to any AEs, and < 1% of women discontinued due to genitourinary symptoms. Overall, > 80% of women reported being "very satisfied" or "satisfied" with study treatment. CONCLUSIONS: In this phase 3 study, the novel vaginal pH regulator demonstrated 86.3% contraceptive effectiveness, was safe and well tolerated, and was highly acceptable. IMPLICATIONS: This novel vaginal pH regulator is a safe, nonhormonal, woman-controlled method of contraception that expands women's options.