A randomized placebo-controlled pilot study of the effect and duration of Amphora, a multipurpose vaginal pH regulator, on vaginal pH

Abstract

The vaginal microbiome is a highly dynamic environment that is altered with changes in vaginal pH [1,2]. Even small increases in vaginal pH, such as those associated with menstruation, can cause a shift in the predominant bacterial species present in the vagina [1,3].An acidic pH and colonization with Lactobacillus species (LB) are important components of the vagina's natural defense mechanisms against infections [2,4,5]. In vitro, LB acidify their growth medium to a pH of 3.2 to 4.8, a range that is similar to the average healthy vagina [6,7]. However, disruption of this equilibrium may reduce the presence of LB, which causes a subsequent rise in vaginal pH and possible overgrowth of abnormal flora, since many pathogenic organisms require a pH > 4.5 for growth [8][9][10][11][12][13][14][15]. Therefore, maintaining a vaginal pH around 4.0 to 4.5 could help prevent recurrence of bacterial vaginosis (BV) [6]. The development of options for prevention of recurrent BV is of significant interest, as women who are diagnosed with BV may have a greater than 50% risk of recurrence in the subsequent 12 months [16]. In addition, BV has been associated with increased risk of pre-term delivery, low birth weight infants, miscarriage, and acquisition of sexu-ally transmitted infections [17,18].Recently, there has been interest in developing a vaginal preparation with the capacity to work as both a contraceptive and a microbicide. Amphora vaginal gel (AVG) is a multipurpose vaginal pH regulator (MVP-R) under evaluation as an on-demand contraceptive (NCT03243305), to prevent certain sexually transmitted infections (NCT03107377), and potentially reduce recurrence of BV after intravaginal administration. It has been demonstrated that AVG is well-tolerated and results in a low vaginal pH; however, the duration of this effect has not been clearly established [6,19]. Therefore, the primary objective of this study (NCT02693418) was to assess change from baseline in vaginal pH after intravaginal administration of a single dose (5, 4, or 3 grams) of AVG, placebo gel, or no treatment, and to measure the duration of this change. Materials and Methods