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.

A Phase 3, Multicenter, Prospective, Open-Label Study to Evaluate the Safety of a Single Dose of Secnidazole 2 g for the Treatment of Women and Postmenarchal Adolescent Girls with Bacterial Vaginosis.

BACKGROUND: A novel formulation of secnidazole is under development in the United States for the treatment of bacterial vaginosis (BV). Efficacy and safety of other formulations of secnidazole have been reported. The objective of this study is to evaluate the safety of a single-dose oral granule formulation of secnidazole in a U.S. population of women with BV. METHODS: In this open-label study, patients were enrolled based on the following criteria: off-white, thin, homogeneous vaginal discharge; vaginal pH ≥4.7; presence of ≥20% clue cells; and positive potassium hydroxide whiff test. Eligible patients received a single dose of secnidazole 2 g at baseline. Patients were contacted on days 8-10 and were assessed for safety at an end-of-study visit (days 21-30). Additional endpoints included investigator assessment of the need for additional treatment and a post hoc analysis of clinical response to treatment. RESULTS: Of 321 patients, 283 (88.2%) completed the study. The mean age was 32 ± 8.5 years; most patients were white (51.4%) or black/African American (46.1%). Most (79.1%) reported ≤3 episodes of BV in the past year. The overall number of treatment-emergent adverse events (TEAEs) was 95 (29.6%), of which 53 (16.5%) were treatment related. Common treatment-related TEAEs were vulvovaginal mycotic infection (5.3%), nausea (4.4%), and dysgeusia (3.1%). The proportion of patients not requiring additional BV treatment, as assessed by investigators, was 72.5%. CONCLUSIONS: Single-dose secnidazole 2 g was well tolerated, with a low overall number of TEAEs, most of which were mild to moderate.

Tranexamic acid increases hemoglobin and ferritin levels in women with heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) is the most common cause of iron deficiency anemia (IDA) in women. A novel, modified-release oral formulation of tranexamic acid (TA) designed to reduce gastrointestinal side effects was approved recently for treatment of HMB. We assessed improvements in objective laboratory measures of IDA in women with self-reported HMB who received long-term TA therapy. METHODS: Women enrolled in a long-term, open-label, multicenter study self-medicated with TA 3.9 g/day administered as 1.3 g orally up to three times daily for 5 days/menstrual cycle for 27 cycles. Oral iron therapy was required if serum hemoglobin (Hgb) levels decreased to <11 g/dL. RESULTS: A total of 723 women (mean age 38.3 years) were included in the intent-to-treat (ITT) population. Significant increases in mean serum Hgb and ferritin were observed throughout the study (p<0.01). Among 191 patients with low Hgb (<12 g/dL) at baseline, mean serum Hgb increased by ≥0.71 g/dL after the third cycle and all subsequent assessments (p<0.001). After 3 and 27 cycles, 34.1% and 45.7%, respectively, of patients with low Hgb at baseline shifted to within normal range, respectively. Among 233 patients with low ferritin (<10 ng/mL) at baseline, mean serum ferritin increased by >5.38 ng/mL after cycles 15 and 27. After 6 and 27 cycles, 35.2% and 58% of patients, respectively, with low ferritin levels at baseline shifted to within normal range. CONCLUSIONS: Long-term self-medication with this novel TA formulation improved Hgb and ferritin levels in women with self-reported HMB.

Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial.

OBJECTIVE: To assess the efficacy and safety of an oral formulation of tranexamic acid for the treatment of heavy menstrual bleeding. METHODS: Adult women with heavy menstrual bleeding (mean menstrual blood loss 80 mL or more per cycle) were enrolled in a double-blind, placebo-controlled study. After two pretreatment menstrual cycles, women were randomized to receive tranexamic acid 3.9 g/d or placebo for up to 5 days per menstrual cycle through six cycles. To meet the prespecified three-component primary efficacy end point, mean reduction in menstrual blood loss from baseline with tranexamic acid treatment needed to be 1) significantly greater than placebo, 2) greater than 50 mL, and 3) greater than a predetermined meaningful threshold (36 mL or higher). Health-related quality of life was measured using a validated patient-reported outcome instrument. RESULTS: Women who received tranexamic acid (n=115) met all three primary efficacy end points: first, a significantly greater reduction in menstrual blood loss of -69.6 mL (40.4%) compared with -12.6 mL (8.2%) in the 72 women who received placebo (P<.001); reduction of menstrual blood loss exceeding a prespecified 50 mL; and last, reduction of menstrual blood loss considered meaningful to women. Compared with women receiving placebo, women treated with tranexamic acid experienced significant improvements in limitations in social or leisure and physical activities, work inside and outside the home, and self-perceived menstrual blood loss (P<.01). The majority of adverse events were mild to moderate in severity, and the incidence of gastrointestinal adverse events was comparable with placebo. CONCLUSION: In this study, a new oral tranexamic acid treatment was well tolerated and significantly improved both menstrual blood loss and health-related quality of life in women with heavy menstrual bleeding. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00386308. LEVEL OF EVIDENCE: I.