Efficacy and Safety of Single Oral Dosing of Secnidazole for Trichomoniasis in Women: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Delayed-Treatment Study.

BACKGROUND: Trichomonas vaginalis is the most prevalent nonviral sexually transmitted infection. We evaluated the efficacy and safety of secnidazole vs placebo in women with trichomoniasis. METHODS: Women with trichomoniasis, confirmed by a positive T. vaginalis culture, were randomized to single-dose oral secnidazole 2 g or placebo. The primary endpoint was microbiological test of cure (TOC) by culture 6-12 days after dosing. At the TOC visit, participants were given the opposite treatment. They were followed for resolution of infection afterward and offered treatment at subsequent visits, if needed. Fifty patients per group (N = 100) provided approximately 95% power to detect a statistically significant difference between treatment groups. RESULTS: Between April 2019 and March 2020, 147 women enrolled at 10 sites in the United States. The modified intention-to-treat (mITT) population included 131 randomized patients (secnidazole, n = 64; placebo, n = 67). Cure rates were significantly higher in the secnidazole vs placebo group for the mITT population (92.2% [95% confidence interval {CI}: 82.7%-97.4%] vs 1.5% [95% CI: .0%-8.0%]) and for the per-protocol population (94.9% [95% CI: 85.9%-98.9%] vs 1.7% [95% CI: .0%-8.9%]). Cure rates were 100% (4/4) in women with human immunodeficiency virus (HIV) and 95.2% (20/21) in women with bacterial vaginosis (BV). Secnidazole was generally well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were vulvovaginal candidiasis and nausea (each 2.7%). No serious TEAEs were observed. CONCLUSIONS: A single oral 2 g dose of secnidazole was associated with significantly higher microbiological cure rates vs placebo, supporting a role for secnidazole in treating women with trichomoniasis, including those with HIV and/or BV. CLINICAL TRIALS REGISTRATION: NCT03935217.

A phase 3, randomized, controlled trial of Astodrimer 1% Gel for preventing recurrent bacterial vaginosis.

OBJECTIVE: The objective of the study was to confirm the efficacy and safety of Astodrimer 1% Gel to prevent recurrence of bacterial vaginosis. STUDY DESIGN: 864 women with a diagnosis of bacterial vaginosis and a history of recurrent bacterial vaginosis were enrolled in North America and first received oral metronidazole (500 mg twice daily for 7 days). Women successfully treated with metronidazole were randomly assigned 1:1 to Astodrimer 1% Gel (N = 295) or placebo (N = 291) at a dose of 5 g vaginally every second day for 16 weeks, and followed for a further 12 weeks off-treatment. The primary endpoint was recurrence of bacterial vaginosis (presence of ≥3 Amsel criteria) at or by Week 16. Secondary endpoints included time to recurrence, and recurrence of subject-reported symptoms. Adverse events were monitored throughout the study. RESULTS: Astodrimer 1% Gel was superior to placebo for the primary and many secondary efficacy measures. At or by Week 16, bacterial vaginosis recurred in 44.2 % (130/294) of women receiving astodrimer and 54.3 % (158/291) receiving placebo (P = .015). Time to recurrence of bacterial vaginosis was significantly longer for women receiving astodrimer compared with placebo (Kaplan-Meier survival curves, P = .007). Recurrence of subject-reported symptoms at or by Week 16 was also significantly lower in the astodrimer arm compared with placebo (vaginal odor and/or discharge, 27.9 % [75/269] vs 40.6 % [108/266], P = .002). A significantly lower proportion of patients receiving astodrimer compared with placebo had recurrence of bacterial vaginosis at or by Week 16 by other secondary measures, including individual Amsel criteria (vaginal discharge and clue cells) and Nugent score 7-10. Recurrence of subject-reported vaginal odor and/or discharge was significantly lower in the astodrimer arm compared with placebo up to 8 weeks after cessation of therapy (36.1 % [97/269] vs 45.5 % [121/266], P = .027).Adverse events were infrequent, and rates were generally similar between placebo and astodrimer groups. Vulvovaginal candidiasis and urinary tract infection occurred more often in women receiving astodrimer. CONCLUSIONS: Astodrimer 1% Gel, administered every second day for 16 weeks, was effective and superior to placebo for prevention of recurrent bacterial vaginosis in women with a history of recurrent BV, and was well-tolerated.

Two phase 3, double-blind, placebo-controlled studies of the efficacy and safety of Astodrimer 1% Gel for the treatment of bacterial vaginosis.

OBJECTIVE: Astodrimer is a dendrimer formulated in a vaginal gel to treat bacterial vaginosis (BV) and prevent recurrence. The objective of these studies was to confirm the efficacy and safety of Astodrimer 1 % Gel for treatment of BV. STUDY DESIGN: Women with bacterial vaginosis were randomized 1:1 to Astodrimer 1 % Gel (Study 1 conducted in the United States, N = 127; Study 2 conducted in the United States, Germany and Belgium, N = 128) or placebo gel (Study 1, N = 123; Study 2, N = 123) at a dose of 5 g vaginally once daily for 7 days. The primary endpoint was clinical cure, defined as i) absence of bacterial vaginosis vaginal discharge; ii) <20 % clue cells; and iii) negative whiff test at day 9-12. Secondary efficacy analyses included clinical cure at day 21-30. Other endpoints at days 9-12 and 21-30 included Nugent cure (Nugent score ≤3), absence of symptoms, and adverse events. The primary analysis in the modified intent-to-treat population used the Cochran Mantel Haenszel test stratified by analysis center with a two-sided significance level of α = .05. RESULTS: Astodrimer 1 % Gel was superior to placebo for the primary and selected secondary efficacy measures. Clinical cure rates at day 9-12 were 50.4 % (59/117) vs 16.5 % (19/115, P < .001) (Study 1) and 56.7 % (68/120) vs 21.4 % (25/117, P < .001) (Study 2) for astodrimer vs placebo. At day 21-30, clinical cure results showed a similar trend but the difference to placebo was not statistically significant. Nugent cure rates at day 9-12 were 12.8 % (15/117) vs 2.6 % (3/115, P = .004) (Study 1) and 13.3 % (16/120) vs 5.1 % (6/117, P = .030) (Study 2) for astodrimer vs placebo. A greater proportion of women receiving astodrimer reported absence of vaginal discharge and absence of vaginal odor at day 9-12 and day 21-30 compared with placebo. Adverse events were generally mild and self-limiting. For the combined studies, adverse events potentially related to treatment occurred in 14.7 % (37/252) of astodrimer patients vs 9.4 % (23/244) for placebo, including vulvovaginal candidiasis reported for 2.4 % (6/252) of astodrimer patients. CONCLUSION: These results support a role for Astodrimer 1 % Gel as an effective, safe and well-tolerated treatment for women with bacterial vaginosis.