Trends in sexually transmitted infections in general practice 1990-2000: population based study using data from the UK general practice research database

Objective: To describe the contribution of primary care to the diagnosis and management of sexually transmitted infections in the United Kingdom, 1990-2000, in the context of increasing incidence of infections in genitourinary medicine clinics. Design: Population based study. Setting: UK primary care. Participants: Patients registered in the UK general practice research database. Main outcome measures: Incidence of diagnosed sexually transmitted infections in primary care and estimation of the proportion of major such infections diagnosed in primary care. Results: An estimated 23.0% of chlamydia cases in women but only 5.3% in men were diagnosed and treated in primary care during 1998-2000, along with 49.2% cases of non-specific urethritis and urethral discharge in men and 5.7% cases of gonorrhoea in women and 2.9% in men. Rates of diagnosis in primary care rose substantially in the late 1990s. Conclusions: A substantial and increasing number of sexually transmitted infections are diagnosed and treated in primary care in the United Kingdom, with sex ratios differing from those in genitourinary medicine clinics. Large numbers of men are treated in primary care for presumptive sexually transmitted infections

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

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. Conclusion Astodrimer Gel once daily for 7 days was superior to placebo for treatment of bacterial vaginosis and was well-tolerated. The 1% dose consistently showed the strongest efficacy across endpoints. These results support a role for Astodrimer Gel, 1%, as an effective treatment for bacterial vaginosis

Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial

Astodrimer sodium is a dendrimer molecule with antiviral and virucidal activity against SARS-CoV-2 and other respiratory viruses in vitro, and has previously been shown to be safe and well tolerated, and not systemically absorbed, when applied to the vaginal mucosa. To investigate its potential utility as a topical antiviral, astodrimer sodium has been reformulated for application to the nasal mucosa to help reduce viral load before or after exposure to respiratory infection. The current investigation assessed the safety, tolerability and absorption of astodrimer sodium 1% antiviral nasal spray. This was a single-centre, double-blinded, randomized, placebo-controlled, exploratory clinical investigation. Forty healthy volunteers aged 18 to 65 years with no clinically significant nasal cavity examination findings were randomized 3:1 to astodrimer sodium nasal spray (N = 30) or placebo (N = 10) at an Australian clinical trials facility. An initial cohort of participants (N = 12 astodrimer, N = 4 placebo) received a single application (one spray per nostril) to assess any acute effects, followed by a washout period, before self-administering the spray four times daily for 14 days to represent an intensive application schedule. Extent of absorption of astodrimer sodium via the nasal mucosa was also assessed in this cohort. A second cohort of participants (N = 18 astodrimer, N = 6 placebo) self-administered the spray four times daily for 14 days. The primary endpoint was safety, measured by frequency and severity of treatment emergent adverse events (TEAEs), including clinically significant nasal cavity examination findings, in the safety population (all participants randomized who administered any spray). Participants were randomized between 6 January 2021 and 29 March 2021. TEAEs occurred in 8/10 (80%) participants in the placebo arm and 19/30 (63.3%) participants in the astodrimer sodium arm; all were of mild intensity. TEAEs considered potentially related to study product occurred in 5/10 (50%) participants receiving placebo and 10/30 (33.3%) of participants receiving astodrimer sodium. No participants experienced serious AEs, or TEAEs leading to withdrawal from the study. No systemic absorption of astodrimer sodium via the nasal mucosa was detected. Astodrimer sodium nasal spray was well tolerated and is a promising innovation warranting further investigation for nasal administration to potentially reduce infection and spread of community acquired respiratory virus infections. Trial Registration: ACTRN12620001371987, first registered 22-12-2020 (Australia New Zealand Clinical Trials Registry, https://anzctr.org.au/)

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