By Rebecca H. Allen, MD, MPH, Editor
SYNOPSIS: In this single-arm, open-label, Phase III study of a novel vaginal pH regulator gel among 1,384 sexually active women aged 18 to 35 years, the seven-cycle cumulative pregnancy rate was 13.7% (95% confidence interval, 10.0% to 17.5%).
SOURCE: Thomas MA, Chappell BT, Maximos B, et al. A novel vaginal pH regulator: Results from the phase 3 AMPOWER contraception clinical trial. Contracept X 2020;2:100031.
The authors of this study evaluated the contraceptive effectiveness of a novel nonhormonal vaginal pH regulator gel that contains three active ingredients: L-lactic acid, citric acid, and potassium bitartrate. The goal of the gel is to maintain an acidic environment in the vagina inhospitable to sperm. The brand name of the product is Phexxi.
This was a multicenter, single-arm, open-label, Phase III trial performed to obtain Food and Drug Administration (FDA) approval for a vaginal contraceptive gel that regulates the vaginal pH. The primary endpoint was the seven-cycle cumulative pregnancy rate with typical use. The study had 90% power to ensure the upper limit of the 95% confidence interval (CI) of the pregnancy rate to be no more than 21%. Eligibility criteria included females between the ages of 18 to 35 years who were deemed at risk of pregnancy with normal menstrual cycles.
Women were asked to have at least three acts of sexual intercourse per month with their male partner. Exclusion criteria included women with frequent urinary tract infections (UTIs) and vaginal infections, pregnancy, breastfeeding, and infertility. The vaginal gel was administered immediately before or up to one hour prior to intercourse. Women maintained electronic diaries to record adverse effects, acts of vaginal intercourse, use of concomitant medications, and menses. Women were followed for seven cycles, and at the end of the study were asked to report their satisfaction with the study drug. Qualifying cycles for analysis had to include a 21- to 35-day cycle length, no backup or emergency contraception, and at least one recorded act of vaginal intercourse in that cycle.
The investigators enrolled 1,384 women across 112 study sites between July 2017 and November 2018. The mean age was 27.7 (± 4.5) years, mean body mass index of 28.8 (± 8.1) kg/m2, and 37.5% of the sample was nulligravid. Of the women enrolled, 46.7% completed the entire seven cycles. The remainder left the study early, with being lost to follow up (18.1%) or withdrawal by the subject (12.3%) most common. Nevertheless, 1,114 women were included in the efficacy analysis based on the cycles they contributed. For contraceptive efficacy, 101 pregnancies occurred, resulting in a seven-cycle cumulative pregnancy percentage of 13.7% (95% CI, 10.0% to 17.5%), which was below the pre-specified upper boundary 95% CI of ≤ 21%. The most frequent adverse events reported by women were vulvovaginal burning sensation (20%), vulvovaginal pruritis (11.2%), UTI (5.7%), vulvovaginal pain (3.8%), vaginal candidiasis (2.9%), and bacterial vaginosis (2.8%). However, less than 2% of women discontinued the study because of an adverse event, and more than 82% were very satisfied or satisfied with the contraceptive vaginal gel.
The goal of this product was to create a nonhormonal, female-controlled contraceptive that could be used when needed. The gel maintains the acidic environment of the vagina, even in the presence of alkaline sperm. The gel’s viscosity is such that it adheres to the vaginal walls for up to eight to 10 hours. The gel can be used with any type of condom and diaphragm, but not with the contraceptive vaginal ring. According to the authors, the rates of vulvovaginal burning and pruritis are similar to those seen with male and female condoms. Unlike over-the-counter spermicides, this new vaginal pH regulator gel (Phexxi) is available only by prescription. It is dispensed in single-use disposable applicators in a box of 12, with instructions to insert immediately before or one hour prior to vaginal intercourse.
The failure rate in this clinical trial was 13.7%, which may or may not reflect typical use in the real world, since women in the study were subject to study reminders and electronic diaries that may have changed their behavior. This puts this method in a similar range to spermicides (typical use failure rate, 21%; perfect use failure rate, 16%), diaphragm (typical use, 17%; perfect use, 16%), the female condom (typical use, 21%; perfect use, 5%), and the male condom (typical use, 13%; perfect use, 2%).1 The product obtained FDA approval on May 22, 2020, and now is available on the market.
Any contraceptive new to the menu of options is a welcome addition because women need access to multiple types of contraceptives throughout their lives. The company is marketing this as a nonhormonal option for patients that can be used at the moment of sexual activity. It is not clear to me how this product differs in that sense from spermicides, and we do not have any head-to-head trials comparing spermicides to this product in terms of efficacy and side effects. Nevertheless, for patients who do not want to use condoms or are seeking to augment the contraceptive efficacy of condoms or other methods and are looking for a contraceptive that does not need to be used daily, this is another option. It is possible women will see this as a more natural alternative compared to spermicides because it keeps the vaginal environment acidic rather than using a chemical (nonoxynol-9) that kills sperm. However, I suspect this product will not be widely used until the company applies for it to be moved to over-the-counter status.
- Trussell J, Aiken ARA, Micks E, Guthrie KA. Efficacy, safety, and personal considerations. In: Hatcher RA, Nelson AL, Trussell R, et al. Contraceptive Technology. 21st ed. Ardent Media Inc.;2018:95-128.