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

Chavoustie, Steven; Carter, Belvia A.; Waldbaum, Arthur; Donders, Gilbert; Peters, Klaus; Schwebke, Jane R.; Paull, Jeremy Ra; Price, Clare; Castellarnau, Alex; McCloud, Philip; Kinghorn, G R

doi:10.1016/j.ejogrb.2019.11.032

Cited by 25 publications

(43 citation statements)

References 18 publications

(21 reference statements)

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“…Nevertheless, the reported adverse events were mostly mild to moderate, tolerable and self-limiting. The results of this trial supported the assertion that astodrimer 1% gel is safe and effective for the treatment of BV in women [166]. Curatek Pharmaceuticals completed another multi-centre phase 3 study of terconazole gel for the treatment of vaginal infection.…”

Section: Progresses Of Advanced Drug Delivery In Clinical Researchsupporting

confidence: 58%

Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

et al. 2020

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An optimal host–microbiota interaction in the human vagina governs the reproductive health status of a woman. The marked depletion in the beneficial Lactobacillus sp. increases the risk of infection with sexually transmitted pathogens, resulting in gynaecological issues. Vaginal infections that are becoming increasingly prevalent, especially among women of reproductive age, require an effective concentration of antimicrobial drugs at the infectious sites for complete disease eradication. Thus, topical treatment is recommended as it allows direct therapeutic action, reduced drug doses and side effects, and self-insertion. However, the alterations in the physiological conditions of the vagina affect the effectiveness of vaginal drug delivery considerably. Conventional vaginal dosage forms are often linked to low retention time in the vagina and discomfort which significantly reduces patient compliance. The lack of optimal prevention and treatment approaches have contributed to the unacceptably high rate of recurrence for vaginal diseases. To combat these limitations, several novel approaches including nano-systems, mucoadhesive polymeric systems, and stimuli-responsive systems have been developed in recent years. This review discusses and summarises the recent research progress of these novel approaches for vaginal drug delivery against various vaginal diseases. An overview of the concept and challenges of vaginal infections, anatomy and physiology of the vagina, and barriers to vaginal drug delivery are also addressed.

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Section: Progresses Of Advanced Drug Delivery In Clinical Researchsupporting

confidence: 58%

Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

et al. 2020

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“…The product acts locally and is not systemically absorbed, offering patients and clinicians an additional safe treatment option that avoids potential issues associated with existing conventional antibiotics, such as high rates of candidiasis and antibiotic resistance. The 1% astodrimer dose consistently showed the strongest efficacy across primary and secondary endpoints, and was selected for assessment in phase 3 studies to confirm efficacy and safety findings [28].…”

Section: Strengths and Limitationsmentioning

confidence: 99%

A phase 2, double-blind, multicenter, randomized, placebo-controlled, dose‑ranging study of the efficacy and safety of Astodrimer Gel for the treatment of bacterial vaginosis

et al. 2020

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Background Astodrimer Gel contains a novel dendrimer intended to treat and prevent bacterial vaginosis. We assessed the efficacy and safety of Astodrimer Gel for treatment of bacterial vaginosis. Methods 132 women with bacterial vaginosis were randomized 1:1:1:1 to Astodrimer 0.5% (N = 34), 1% (N = 33), or 3% (N = 32) Gel or hydroxyethyl cellulose placebo gel (N = 33) at a dose of 5 g vaginally once daily for 7 days at 6 centers in the United States. The primary endpoint was clinical cure (no bacterial vaginosis vaginal discharge and no more than one of 1) vaginal pH �4.5; 2) �20% clue cells; or 3) positive whiff test) at study days 21-30. Secondary analyses included clinical cure at study days 9-12, patient-reported symptoms, acceptability and adverse events. Results The Astodrimer 1% Gel dose was superior to placebo for the primary and selected secondary efficacy measures in the modified intent-to-treat population. Clinical cure rates at day 9-12 were superior to placebo for the Astodrimer 3%, 1% and 0.5% Gel groups (62.5% [15/ 24; P = .002], 74.1% [20/27; P < .001], and 55.2% [16/29; P = .001], respectively, vs. 22.2% [6/27]). At day 21-30, clinical cure rates were 46.2% (12/26) for the 1% dose vs. 11.5% for placebo (3/26; P = .006). A greater proportion of patients reported absence of vaginal discharge and vaginal odor at day 9-12 and day 21-30 for Astodrimer Gel groups compared with placebo. Adverse events considered potentially treatment-related occurred in only 25% of Astodrimer Gel-treated patients vs. 22% of placebo patients.

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“…The potential advantages of astodrimer sodium over other technologies include its lack of systemic absorption following topical application (Chen et al, 2009;O'Loughlin et al, 2010;McGowan et al, 2011). In addition, the SI of astodrimer sodium for SARS-CoV-2 is high and in a vaginal gel formulation (10 mg/mL), the compound has been shown to be safe and effective in phase and large phase trials for treatment and prevention of BV (Schwebke et al, 2019;Chavoustie et al, 2020;Waldbaum et al, 2020) and is now marketed in Europe, Australia, New Zealand and several countries in Asia. Astodrimer sodium is also the active antiviral substance in VivaGel ® condom products that have marketing authorization in Europe, Japan, Australia/New Zealand and Canada.…”

Section: Discussionmentioning

confidence: 99%

Virucidal and antiviral activity of astodrimer sodium against SARS-CoV-2 in vitro

Paull

Heery

Bobardt

et al. 2020

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An effective response to the ongoing coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will require a range of complementary preventive modalities. The current studies were conducted to evaluate the in vitro SARS-CoV-2 antiviral activity of astodrimer sodium, a dendrimer with broad spectrum antimicrobial activity, including against enveloped viruses in in vitro and in vivo models, that is marketed for antiviral and antibacterial applications. We report that astodrimer sodium inhibits replication of SARS-CoV-2 in Vero E6 cells when added to cells 1-hour prior to or 1-hour post infection, with 50% effective concentrations reducing virus-induced cytopathic effect (EC50) ranging from 0.090 to 0.742 μM (0.002 to 0.012 mg/mL). The selectivity index (SI) in these assays was as high as 2197. Astodrimer sodium was also effective in a virucidal evaluation when mixed with virus for 1 hour prior to infection of cells (EC50 1.83 μM [0.030 mg/mL]). Results from a time of addition study, which showed infectious virus was below the lower limit of detection at all time points tested, were consistent with the compound inhibiting early virus entry steps. The data were similar for all investigations and were consistent with the potent antiviral activity of astodrimer sodium being due to inhibition of virus-host cell interactions, as previously demonstrated for other viruses. Further studies will confirm if astodrimer sodium binds to SARS-CoV-2 spike protein and physically blocks initial association of the virus with heparan sulfate proteoglycans on the host cell. Given the in vitro effectiveness and significantly high SI, astodrimer sodium warrants further investigation for potential as a nasally administered or inhaled antiviral agent for SARS-CoV-2 prevention and treatment applications.

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

Cited by 25 publications

References 18 publications

Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

A phase 2, double-blind, multicenter, randomized, placebo-controlled, dose‑ranging study of the efficacy and safety of Astodrimer Gel for the treatment of bacterial vaginosis

Virucidal and antiviral activity of astodrimer sodium against SARS-CoV-2 in vitro

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