Single Dose Of Secnidazole Research Articles

(034) Secnidazole for Trichomoniasis: Results from a Clinical Trial with Women and a Systematic Literature Review for Men

Abstract Introduction Trichomoniasis is the most prevalent non-viral sexually transmitted infection (STI) in the world, affecting ~4.1% of women and ~1.3% of men aged 40–59 in the United States. Women with T. vaginalis are at 2- to 3-fold increased risk for acquiring human immunodeficiency virus (HIV). Trichomoniasis is also associated with vaginitis, pelvic inflammatory disease, post-hysterectomy cuff cellulitis and other STIs. In addition, it can cause infertility and increase a woman’s risk for adverse pregnancy outcomes including preterm birth, premature rupture of membranes, and delivery of low birthweight infants. In men, trichomoniasis is associated with non-gonococcal urethritis, although men are frequently asymptomatic and may seek treatment only after knowing that their female partners are infected. Current CDC treatment guidelines recommend concurrent treatment of both partners to prevent transmission and reinfection. Objectives To evaluate the efficacy and tolerability of secnidazole in women and men with trichomoniasis. Because logistical and statistical considerations precluded the inclusion of men in the clinical trial, we conducted a systematic literature search (19May2020) to identify other studies of secnidazole in male patients with trichomoniasis. Secnidazole is FDA-approved for the treatment of bacterial vaginosis in women. Methods In a randomized clinical trial (RCT), women with a diagnosis of trichomoniasis received a single, oral dose of secnidazole 2g or placebo at baseline (Visit 1). At Visit 2 (days 6–12), they were evaluated for test of cure (TOC) and switched to the opposite treatment. The primary endpoint was microbiological cure (ie, InPouch™ culture negative for T. vaginalis) at the TOC visit. Adverse events (AEs) were monitored. A trained research associate used ProQuest Dialog™ to search BIOSIS Previews, EMBASE, and MEDLINE using search terms related to secnidazole, clinical trials, men/males, and trichomoniasis. Results For the RCT, 147 women were enrolled; the modified intent-to-treat population included 131 randomized patients. Cure rates were 92.2% and 1.5% for secnidazole and placebo (P<0.001). The most commonly reported AEs were vulvovaginal candidiasis (2.7%) and nausea (2.7%). No serious AEs were reported. For the systematic review, 4 studies were identified, which included 211 men who received secnidazole for treatment of trichomoniasis. In one study that included only men (n=85), the cure rate 5 days after treatment was 100%. In the 3 studies that included men and women, cure rates were 92–97%. For studies reporting AEs, the most common were nausea (4–9%), and dyspepsia (0.5–1.1%). Pharmacokinetics data showed no clinically meaningful differences in secnidazole exposure (Cmax, AUC) between men and women; however, the mean (±SD) half-life (hours) was longer in men versus women (20.2 hours [±3.1] vs. 14.3 hours [±1.3]). Conclusions In a RCT of women with trichomoniasis, cure rates were significantly higher after single-dose secnidazole versus placebo, and tolerability profiles were comparable between treatment groups. In a systematic literature review of secnidazole for trichomoniasis in men, cure rates, tolerability, and pharmacokinetics data were comparable to those in women. Disclosure Yes - Lupin Pharmaceuticals, Inc. Industry initiated, executed and funded study – Yes.

A phase 3, multi-center, prospective, randomized, placebo-controlled, delayed treatment, double-blind study to evaluate the effectiveness and safety of a single oral dose of 2 grams of secnidazole for the treatment of trichomoniasis in women

The objective of this study was to evaluate the efficacy and safety of single-dose secnidazole 2g oral granules in women with trichomoniasis. (Secnidazole is approved by the FDA to treat bacterial vaginosis).

An Integrated Efficacy and Safety Analysis of Single-Dose Secnidazole 2\xa0g in the Treatment of Bacterial Vaginosis

Bacterial vaginosis (BV) is the most common gynecologic infection in women aged 14 to 49 years. Currently recommended treatments require extended dosing and are thus associated with poor adherence. A single-dose oral granule formulation of secnidazole 2 g (SOLOSEC™ [secnidazole], Symbiomix Therapeutics, a Lupin company, Baltimore, MD), a 5-nitroimidazole antibiotic with antimicrobial activity, has been approved by the US Food and Drug Administration for the treatment of BV in adult women. As part of the US registration package, two randomized, double-blind, placebo-controlled clinical studies were conducted to confirm the efficacy and safety of a novel single-dose oral formulation of secnidazole 2 g. This is an integrated analysis of efficacy and safety results from these studies, pivotal study 1 and pivotal study 2. By combining the results of the two studies, relevant information is presented especially when considering the effect of secnidazole on patients with recurrent episodes of BV and the difference in effect on patients of black race. Single-dose secnidazole 2 g was statistically superior to placebo on all primary and secondary efficacy outcomes in both trials, including clinical outcome responder rate (P < 0.001), achievement of Nugent scores in the normal range of 0 to 3 (P < 0.001), greater numbers of patients as therapeutic outcome responders at the test of cure/end of study visit on days 21–30 (P < 0.001), and fewer patients requiring additional treatment at the test of cure/end of study visit (P < 0.001), supporting the role for single oral dose secnidazole 2 g granules as treatment for women with BV.

An integrated efficacy and safety analysis of single-dose secnidazole 2 g granules in the treatment of bacterial vaginosis from pivotal phase 2 and phase 3 trials

To conduct an integrated analysis of the efficacy and safety of secnidazole in a large population from pivotal clinical trials.

Secnidazole: next-generation antimicrobial agent for bacterial vaginosis treatment.

Secnidazole is a next-generation 5-nitroimidazole approved for more than three decades in Europe, Asia, South America and Africa and recently in the USA as a single-dose (2g) treatment of bacterial vaginosis (BV). Secnidazole is characterized by potent in vitro antimicrobial activity against BV-associated pathogens, as well as prolonged terminal elimination half-life and systemic exposure. These characteristics form the basis of effective and safe treatment of BV with a 2-g single-dose secnidazole regimen, which was recently confirmed in double-blind, placebo-controlled clinical trials conducted in the USA. The option to treat BV with single-dose secnidazole not only cures the primary infection but also may diminish risks of serious sequelae of untreated or undertreated infection.

A phase-3, double-blind, placebo-controlled study of the effectiveness and safety of single oral doses of secnidazole 2 g for the treatment of women with bacterial vaginosis

A novel single oral dose granule formulation of secnidazole 2 g, a 5-nitroimidazole with a longer half-life (∼17 hours) than metronidazole (∼8 hours), is being developed to treat bacterial vaginosis. We sought to evaluate the effectiveness and safety of single-dose secnidazole 2 g compared to placebo for the treatment of women with bacterial vaginosis. In all, 189 women with bacterial vaginosis were randomized 2:1 to receive a single oral dose of secnidazole 2 g (N= 125) or matched placebo (N= 64) at 21 centers in the United States. The primary endpoint was the proportion of clinical outcome responders, defined as those with: (1) normal vaginal discharge; (2) negative 10% potassium hydroxide whiff test; and (3) <20% clue cells of total epithelial cell count on microscopic examination of the vaginal wet mount, using saline at the test of cure/end of study visit (study days 21-30). Secondary efficacy analyses included clinical cure rates, defined as: (1) responders with normal vaginal discharge; (2) negative potassium hydroxide whiff tests; and (3) clue cells <20% assessed at the interim visit (study days 7-14), and test of cure/end of study (study days 21-30). In addition, based on the 2016 US Food and Drug Administration draft guidance, patients with baseline Nugent scores 7-10 were evaluated for clinical cure using the following clinical assessments on study days 7-14: (1) resolution of the abnormal vaginal discharge; (2) a negative potassium hydroxide whiff test; and (3) clue cells <20%. The study was designed and powered todemonstrate the efficacy of single-dose secnidazole 2 g compared toplacebo; safety and tolerability were also assessed. Due to a prespecified institutional review board-approved protocol calling for withdrawal of randomized, treated patients with a Nugent score <4 or with a separate sexually transmitted infection, this modified intent-to-treat population was the primary analysis population. Statistical comparisons used a stratified Cochran-Mantel-Haenszel test with a .05 level of significance (2-sided). Single-dose secnidazole 2 g was superior to placebo for the primary and all secondary efficacy measures in the modified intent-to-treat population, with clinical outcome responder rates of 53.3% (57/107) vs 19.3% (11/57; P < .001). Clinical cure rates, based on an alternate definition of responder, which accounted for resolution of abnormal discharge consistent with bacterial vaginosis, were consistent with the clinical outcome responder rate analysis (58.9% vs 24.6%; P < .001) for single-dose secnidazole 2 g vs placebo. Clinical cure rates based on the 2016 US Food and Drug Administration guidance were 64.0% vs 26.4% for single-dose secnidazole 2 g vs placebo. Based on the investigator's clinical assessment at the test of cure/end of study visit, significantly more patients receiving single-dose secnidazole 2 g vs placebo required noadditional bacterial vaginosis treatment (68.0% [68/100] vs 29.6% [16/54]; P < .001). Adverse events considered by the investigator to be related to study drug occurred in only 20.0% of single-dose secnidazole 2 g-treated patients vs 10.9% of placebo patients, and they included diarrhea (4.0% vs 1.6%), headache (4.0% vs 3.1%), nausea (4.8% vs 1.6%), and vulvovaginal candidiasis (4.0% vs 3.1%). Single-dose secnidazole 2 g was superior to placebo on all primary and secondary outcomes and was well tolerated; these results support its role for the treatment of women with bacterial vaginosis.

Secnidazole for the treatment of giardiasis in naturally infected cats

Giardia duodenalis causes enteric infections in humans and animals worldwide. Inefficiency of metronidazole is commonly reported in the veterinary clinic routine in the treatment of giardiasis in dogs and cats. The aim of this study was to evaluate the efficacy of secnidazole in the control of infection caused by G. duodenalis in naturally infected cats. For this purpose two experiments were carried out. In the first experiment seven cats were infected with G. duodenalis and treated orally with a single dose of secnidazole (30 mg kg −1). In the second experiment a total of 16 cats were used, 11 naturally infected with G. duodenalis and five negative for the parasite. Animals were divided into three groups: group A ( n = 5) was composed by non-infected animals (negative control), group B ( n = 5) consisted of infected but untreated animals and group C ( n = 6) was composed by cats treated orally with a single dose of secnidazole (30 mg kg −1). Hematological and biochemical parameters were evaluated before and after treatment. The first experiment reached 100% of efficacy because no cysts were found in the feces after treatment. However, doubts about intoxication and interference with hematological and biochemical parameters came to light. No side effects were observed, and the biochemical and hematological parameters of treated animals remained within physiological range, except for one feline which had elevation of liver enzymes. Based on these results, the utilization of secnidazole could be suggested for the treatment of giardiasis in cats. The main advantage of this treatment is that only a single dose is required, which is interesting in animals hard to handle like cats.

Mebendazole Compared with Secnidazole in the Treatment of Adult Giardiasis: A Randomised, No-Inferiority, Open Clinical Trial

To compare the efficacy and safety of mebendazole and secnidazole in the treatment of giardiasis in adult patients, a single-centre, parallel group, open-label, randomized non-inferiority trial was carried out. One-hundred and 26 participants who had symptomatic Giardia mono-infection took part in the study. Direct wet mount and/or Ritchie concentration techniques and physical examinations were conducted at the time of enrolment and at the follow-up visit. The primary outcome measure was parasitological cure, performed at 3, 5, 10 days post-treatment. Negative faecal specimens for Giardia were ensured by the same parasitological techniques. At follow up (day 10) the parasitological cure rate for the per protocol populations was 88.7% (55/62) for MBZ and 91.8% (56/61) for SNZ. For the intention to treat populations the cure rate at the end of treatment was 85.9% (55/64) for MBZ and 90.3% (56/62) for SNZ. Both analyzes showed there was not significant statistical difference between MBZ and SNZ treatment efficacy. Both drugs were well tolerated, only mild, transient and self-limited side effects were reported and did not require discontinuation of treatment. A 3-day course of mebendazole seems to be as efficacious and safe for treatment of giardiasis as a single dose of secnidazole in adults.

Treatment of Bacterial Vaginosis: A Multicenter, Double-Blind, Double-Dummy, Randomised Phase III Study Comparing Secnidazole and Metronidazole

Objective. Multiple-dose metronidazole oral therapy is currently the reference treatment for bacterial vaginosis (BV). This double-blind, double-dummy, noninferiority study compared the efficacy of secnidazole, another nitroimidazole with pharmacokinetics allowing a single dose regimen, to this standard treatment. Methods. A total of 577 patients were randomized to receive metronidazole (500 mg, b.i.d for seven days) or secnidazole (2 g, once). Therapeutic cure at D28 was defined as the resolution of vaginal discharge, positive KOH whiff test, vaginal pH >4.5 and Nugent score >7 on Gram-stained vaginal fluid. Results. According to this primary endpoint, the single-dose secnidazole regimen was shown to be at least as effective as the multiple-dose metronidazole regimen (60.1 % cured women vs 59.5% , 95% confidence interval with a noninferiority margin of 10%: [−0.082; 0.0094]). Safety profiles were comparable in both groups. Conclusion. The secnidazole regimen studied represents an effective, convenient therapeutic alternative that clinicians should consider in routine practice.

Dientamoeba fragilis, a neglected cause of diarrhea, successfully treated with secnidazole

To evaluate the pathogenicity of Dientamoeba fragilis by comparing it with Giardia lamblia and to investigate the effect of a single dose of secnidazole in dientamoebiasis. Stool samples of 400 patients, admitted to the Department of Parasitology, Celal Bayar University, were examined by direct wet mount, formalin-ethyl acetate concentration and trichrome staining methods on three consecutive days. All cases positive for D. fragilis were treated with a single dose of secnidazole, 30 mg/kg for children, and 2 g for adults. On the seventh and fourteenth days, at the end of the treatment, stool samples were examined by the same methods, and clinical symptoms were again evaluated. D. fragilis and G. lamblia were detected in 35 (8.8%) and 34 (8.5%) cases, respectively. The most frequent symptoms were found to be abdominal pain and diarrhea in both infections. D. fragilis was eradicated in 34 (97.1%) patients with a single dose of secnidazole, but a second dose was necessary in one patient. Clinical symptoms disappeared in 27 (77.1%) and decreased in eight (22.9%) cases, after eradication. These data suggested that D. fragilis is as prevalent and pathogenic as G. lamblia, and secnidazole seems to be highly effective in achieving parasitologic and clinical cure. To our knowledge, this is the first report of secnidazole being used in the treatment of dientamoebiasis.

An Overview of the Clinical Experience with Secnidazole in Bacterial Vaginosis and Trichomoniasis

Treatment of vaginal trichomoniasis and, more recently, bacterial vaginosis with a single dose of secnidazole has not been extensively reported in the literature. The objective of the present study was to review the pertinent literature for an evaluation of the efficacy and tolerability of this drug in the treatment of lower genital tract infections.

An Overview of the Clinical Experience of Secnidazole in Giardiasis and Amoebiasis

The experience of the present author in the treatment of 100 patients with symptomatic intestinal amoebiasis demonstrated a clinical cure rate of 83% and a parasitological cure rate of 88% when assessed on day 5 following single dose administration of secnidazole 2g. When 50 asymptomatic amoeba cyst carriers treated with single dose secnidazole 30 mg/kg/bodyweight were compared with 50 similar patients receiving placebo, it was found that 56% of the first group and 24% of the second group became negative, a statistically significant difference favouring those receiving secnidazole. Seven papers dealing with the treatment of acute or chronic amoebiasis were reviewed, and all showed similar or superior results to those of the present author. Four published comparative studies of secnidazole and other amoebicides were also reviewed, all demonstrating superior results with secnidazole.