Lactic acid, citric acid, and potassium bitartrate non-hormonal prescription vaginal pH modulator (VPM) gel for the prevention of pregnancy

References

• Bearak J, Popinchalk A, Ganatra B, et al. Unintended pregnancy and abortion by income, region, and the legal status of abortion: estimates from a comprehensive model for 1990-2019. Lancet Glob Health. 2020 Sep;8(9):e1152–e1161.
   Google Scholar
• Finer LB, Zolna MR. Declines in unintended pregnancy in the United States, 2008-2011. N Engl J Med. 2016 Mar 3; 374(9):211–252.
   Google Scholar
• Bearak J, Popinchalk A, Alkema L, et al. Global, regional, and subregional trends in unintended pregnancy and its outcomes from 1990 to 2014: estimates from a Bayesian hierarchical model. Lancet Glob Health. 2018 Apr;6(4):e380–e389.
   Google Scholar
• Kimberly Daniels JA. Current contraceptive status among women aged 15–49: United States, 2017–2019. USA: Center for Disease Control and Prevention; 2020.
   Google Scholar
• Gilliam ML, Neustadt A, Kozloski M, et al. Adherence and acceptability of the contraceptive ring compared with the pill among students: a randomized controlled trial. Obstet Gynecol. 2010 Mar;115(3):503–510.
   Google Scholar
• Hooper DJ. Attitudes, awareness, compliance and preferences among hormonal contraception users: a global, cross-sectional, self-administered, online survey. Clin Drug Investig. 2010;30(11):749–763.
   Google Scholar
• Higgins JA, Ryder K, Skarda G, et al. The sexual acceptability of intrauterine contraception: a Qualitative Study of Young Adult Women. Perspect Sex Reprod Health. 2015 Sep;47(3):115–122.
   Google Scholar
• Peipert JF, Zhao Q, Allsworth JE, et al. Continuation and satisfaction of reversible contraception. Obstet Gynecol. 2011 May;117(5):1105–1113.
   Google Scholar
• Bitzer J, Simon JA. Current issues and available options in combined hormonal contraception. Contraception. 2011 Oct;84(4):342–356.
   Google Scholar
• Study of contraceptive efficacy & safety of Phexxi™ (previously known as amphora) gel compared to conceptrol vaginal gel. https://ClinicalTrials.gov/show/NCT01306331.
   Google Scholar
• CDC. Contraception 2020 [Accessed 2021 November 15]. Available from: https://www.cdc.gov/reproductivehealth/contraception/
   Google Scholar
• Trussell J, Micks E, Guthrie KA. Efficacy, safety and personal considerations. 21st ed. Hatcher RA, Trussell J, Cwiak C, et al., editor. New York: Ayer Company Publishers; 2018.
   Google Scholar
• Schwartz JL, Lai -J-J, Frezieres R, et al. editor Contraceptive efficacy, safety and acceptability of SILCS, a novel single-sized diaphragm used with contraceptive gel. Contraception Conference: Reproductive Health 2011; 2012; Las Vegas, NV United States.
   Google Scholar
• Van Damme L, Ramjee G, Alary M, et al. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial. Lancet. 2002;360(9338):971–977.
   Google Scholar
• Kaneshiro B, and Aeby T. Long-term safety, efficacy, and patient acceptability of the intrauterine Copper T-380A contraceptive device. Int J Womens Health. Accessed2010 Aug 9; 8:e1152–e1161
   Google Scholar
• Hubacher D, Chen PL, Park S. Side effects from the copper IUD: do they decrease over time? Contraception. 2009 May;79(5):356–362.
   Google Scholar
• Available from: www.goodrx.com
   Google Scholar
• Pallone SR, Bergus GR. Fertility awareness-based methods: another option for family planning. J Am Board Fam Med. 2009 Mar-Apr;22(2):147–157.
   Google Scholar
• Trussell J Aiken ARA, Micks E, and Guthrie KA. Efficacy, safety, and personal considerations. In: Hatcher RA, Nelson AL, Trussell J, et al, editors. Contraceptive Technology. 21st ed. New York, NY: Ayer Company Publishers; 2018. Ch 3 p8. (epub version)
   Google Scholar
• Calliope: the contraceptive pipeline database. Accessed March 15 2022. Available from: https://pipeline.ctiexchange.org/
   Google Scholar
• Darebio. OVAPRENE® Accessed 16 May 2021; Available from: https://darebioscience.com/pipeline/ovaprene/].
   Google Scholar
• Johnston DS, Goldberg E. Preclinical contraceptive development for men and women. Biol Reprod. 2020 Aug 4; 103(2):147–156.
   Google Scholar
• Safety and Acceptability Study of a non-hormonal ring Accessed 16 May 2021. Available from: https://ClinicalTrials.gov/show/NCT03598088 .
   Google Scholar
• ZabBio. Contraceptive ZB-06 2021 Accessed 16 May 2021; Available from: https://www.zabbio.com/contraceptive-hca].
   Google Scholar
• An exploratory study of ZB-06 as a vaginal contraceptive film Accessed 16 May 2021. Available from: https://ClinicalTrials.gov/show/NCT04731818.
   Google Scholar
• Vaginal antibody safety trial: safety study of monoclonal antibodies to reduce the vaginal transmission of Herpes Simplex Virus (HSV) and Human Immunodeficiency Virus (HIV) Accessed 16 May 2021. Available from: https://ClinicalTrials.gov/show/NCT02579083.
   Google Scholar
• Felix Meniez F, Castro A, Ortega A. Use effectiveness of a spermicidal suppository containing benzalkonium chloride. Contraception. 1986;34(4):353–362.
   Google Scholar
• Contraceptive efficacy, tolerance and acceptability of a benzalkonium chloride spermicide cream in women aged over 40 years of age. Accessed: 7 March 2022. Available from: https://ClinicalTrials.gov/show/NCT03102450; .
   Google Scholar
• Xia M, Yang M, Wang Y, et al. dl-Mandelic acid exhibits high sperm-immobilizing activity and low vaginal irritation: a potential non-surfactant spermicide for contraception. Biomed Pharmacother. 2020 Jun;126:110104.
   Google Scholar
• Vivek V, Bhosale OPA, Gaur SPS. Efficacy and safety of herbal spermicidal contraceptive. Consap Curr Sci. 2013;104(12):1701–1703.
   Google Scholar
• Balbach M, Ghanem L, Rossetti T, et al. Soluble adenylyl cyclase inhibition prevents human sperm functions essential for fertilization. Mol Hum Reprod. 2021;27(9). 10.1093/molehr/gaab054.
   Google Scholar
• Shrestha B, Vincent KL, Schaefer A, et al. Hexavalent sperm-binding IgG antibody released from self-dissolving vaginal film enables potent, on-demand non-hormonal female contraception. Proc Natl Acad Sci U S A. 2021;118(48). DOI:10.1073/pnas.2107832118
   Google Scholar
• Anderson RA, Feathergill KA, Waller DP, et al. SAMMA induces premature human acrosomal loss by Ca2+ signaling dysregulation. J Androl. 2006;27(4):568–577.
   Google Scholar
• 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.
   Google Scholar
• Garg S, Anderson RA, Chany CJ 2nd, et al. Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM). Contraception. 2001 Jul;64(1):67–75.
   Google Scholar
• Brown-Woodman PD, Post EJ, Chow PY, et al. Effects of malonic, maleic, citric and caffeic acids on the motility of human sperm and penetration of cervical mucus. Int J Fertil. 1985;30(3):38–44.
   Google Scholar
• Somsak Suthutvoravut S, Kamyarat O. Spermicidal effects of lemon juice and juices from other natural products. Agric Nat Resour. 2016;50(2):133–138.
   Google Scholar
• Bayer LL, Jensen JT. ACIDFORM: a review of the evidence. Contraception. 2014 Jul;90(1):11–18.
   Google Scholar
• Evofem Biosciences I. How phexxi works 2021 [Accessed 2021 Nov 16]. Available from: https://www.phexxi.com/faqs
   Google Scholar
• Administration USFaD. Phexxi US prescribing information; 2020 Accessed 16 May 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208352s000lbl.pdf
   Google Scholar
• Speroff PDD L. A clinical guide for contraception. Philadelphia: Lippincott Williams & Wilkins; 2006.
   Google Scholar
• Amaral E, Perdigão A, Souza MH, et al. Postcoital testing after the use of a bio-adhesive acid buffering gel (ACIDFORM) and a 2% nonoxynol-9 product. Contraception. 2004 Dec;70(6):492–497.
   Google Scholar
• GRIFFISS J, Avery A, Nayak S, et al. Post hoc analysis of a randomized placebo-controlled pilot study on the effect of Amphora®, an acid-buffering vaginal gel, on vaginal pH by baseline vaginal pH level. Fertil Steril. 2018;110(4):e47.
   Google Scholar
• AMP002 Phase III Contraceptive Study Accessed 30 March 2021. Available from: https://ClinicalTrials.gov/show/NCT03243305.
   Google Scholar
• Wilkinson D, Tholandi M, Ramjee G, et al. Nonoxynol-9 spermicide for prevention of vaginally acquired HIV and other sexually transmitted infections: systematic review and meta-analysis of randomised controlled trials including more than 5000 women. Lancet Infect Dis. 2002 Oct;2(10):613–617.
   Google Scholar
• Hillier SL, Moench T, Shattock R, et al. In vitro and in vivo: the story of nonoxynol 9. J Acquir Immune Defic Syndr. 2005 May 1;39(1):1–8.
   Google Scholar
• Tuyama AC, Cheshenko N, Carlucci MJ, et al. ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: optimal candidate for microbicide combinations. J Infect Dis. 2006 Sep 15;194(6):795–803.
   Google Scholar
• Keller MJ, Carpenter CA, Lo Y, et al. Phase I randomized safety study of twice daily dosing of acidform vaginal gel: candidate antimicrobial contraceptive. PLoS One. 2012;7(10):e46901.
   Google Scholar
• Simoes JA, Bahamondes LG, Camargo RP, et al. A pilot clinical trial comparing an acid-buffering formulation (ACIDFORM gel) with metronidazole gel for the treatment of symptomatic bacterial vaginosis. Br J Clin Pharmacol. 2006 Feb;61(2):211–217.
   Google Scholar
• Spencer SE, Valentin-Bon IE, Whaley K, et al. Inhibition of Neisseria gonorrhoeae genital tract infection by leading-candidate topical microbicides in a mouse model. J Infect Dis. 2004 Feb 1 189(3):410–419.
   Google Scholar
• Mayer KH, Peipert J, Fleming T, et al. Safety and tolerability of BufferGel, a novel vaginal microbicide, in women in the United States. Clin Infect Dis. 2001;32(3):476–482.
   Google Scholar
• Abdool Karim SS, Richardson BA, Ramjee G, et al. Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women. Aids. 2011;25(7):957–966.
   Google Scholar
• Effectiveness of BufferGel as a vaginal contraceptive. https://ClinicalTrials.gov/show/NCT00065858.
   Google Scholar
• Wilson JD, Shann SM, Brady SK, et al. Recurrent bacterial vaginosis: the use of maintenance acidic vaginal gel following treatment. Int J STD AIDS. 2005 Nov;16(11):736–738.
   Google Scholar
• Chappell BT, Mena LA, Maximos B, et al. EVO100 prevents chlamydia and gonorrhea in women at high risk of infection. Am J Obstet Gynecol. 2021 Aug;225(2):162.e1–162.e14.
   Google Scholar
• Evaluation of EVO100 for prevention of urogenital chlamydia trachomatis and neisseria gonorrhoeae infection. https://ClinicalTrials.gov/show/NCT04553068.
   Google Scholar
• O’Hanlon DE, Moench TR, Cone RA. In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide. BMC Infect Dis. 2011 Jul 19; 11:200
   Google Scholar
• Andersch B, Forssman L, Lincoln K, et al. Treatment of bacterial vaginosis with an acid cream: a comparison between the effect of lactate-gel and metronidazole. Gynecol Obstet Invest. 1986;21(1):19–25.
   Google Scholar
• Holst E, Brandberg A. Treatment of bacterial vaginosis in pregnancy with a lactate gel. Scand J Infect Dis. 1990;22(5):625–626.
   Google Scholar
• Amaral E, Perdigao A, Souza MH, et al. Vaginal safety after use of a bioadhesive, acid-buffering, microbicidal contraceptive gel (ACIDFORM) and a 2% nonoxynol-9 product. Contraception. 2006 May;73(5):542–547.
   Google Scholar
• Amaral E, Faúndes A, Zaneveld L, et al. Study of the vaginal tolerance to Acidform, an acid-buffering, bioadhesive gel. Contraception. 1999 Dec;60(6):361–366.
   Google Scholar
• von Mollendorf CE, Van Damme L, Moyes JA, et al. Results of a safety and feasibility study of the diaphragm used with ACIDFORM Gel or K-Y Jelly. Contraception. 2010 Mar;81(3):232–239.
   Google Scholar
• Williams DL, Newman DR, Ballagh SA, et al. Phase I safety trial of two vaginal microbicide gels (Acidform or BufferGel) used with a diaphragm compared to KY jelly used with a diaphragm. Sex Transm Dis. 2007 Dec;34(12):977–984.
   Google Scholar
• Anderson DJ, Williams DL, Ballagh SA, et al. Safety analysis of the diaphragm in combination with lubricant or acidifying microbicide gels: effects on markers of inflammation and innate immunity in cervicovaginal fluid. Am J Reprod Immunol. 2009 Feb;61(2):121–129.
   Google Scholar
• Behets FM, Turner AN, Van Damme K, et al. Vaginal microbicide and diaphragm use for sexually transmitted infection prevention: a randomized acceptability and feasibility study among high-risk women in Madagascar. Sex Transm Dis. 2008 Sep;35(9):818–826.
   Google Scholar
• Kulczycki A, Kim DJ, Duerr A, et al. The acceptability of the female and male condom: a randomized crossover trial. Perspect Sex Reprod Health. 2004 May-Jun;36(3):114–119.
   Google Scholar
• Schwartz JL, Poindexter A, Schmitz SW, et al. Male tolerance of ACIDFORM gel. Contraception. 2005 Jun;71(6):443–446.
   Google Scholar
• Zhu Y, Saada J, Bhawana S, et al. Surrogate post-coital testing for contraceptive efficacy against human sperm activity in the ovine vaginal model. Biol Reprod. 2021 Feb 11 104(2):317–324.
   Google Scholar
• Mauck CK, Vincent KL. The postcoital test in the development of new vaginal contraceptives†. Biol Reprod. 2020;103(4):908.
   Google Scholar
• Litschi A, Gordon D, Porter A, et al. Relationships in America survey. The Austin Institute for the Study of Family and Culture. 2014. Available at: https://www.austin-institute.org/research.
   Google Scholar