Study of Efficacy, Cycle Control, and Safety of a NES-E2 Contraceptive Vaginal Ring

Summary

This will be a multi-site, open-label, randomized clinical trial. The investigators will randomize 300 eligible participants in a 1:1 ratio to two different treatment regimens that are to be followed when using a contraceptive vaginal ring delivering a daily dose of Nestorone® and estradiol (NES-E2 CVR).

Timeline

Start

2018-02-12

Primary completion

2021-08-28

Completion

2021-12-14

Publications

• Background Daulaire N, Leidl P, Mackin L et al., Promises to Keep: The Toll of Unintended Pregnancies on Women's Lives in the Developing World. Washington, DC: Global Health Council; 2002; 11.
• Background Speidel JJ, Harper CC, Shields WC. The potential of long-acting reversible contraception to decrease unintended pregnancy. Contraception. 2008 Sep;78(3):197-200. doi: 10.1016/j.contraception.2008.06.001. Epub 2008 Jul 9. No abstract available.
• Background Finer LB, Henshaw SK. Disparities in rates of unintended pregnancy in the United States, 1994 and 2001. Perspect Sex Reprod Health. 2006 Jun;38(2):90-6. doi: 10.1363/psrh.38.090.06.
• Background Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update. 2006 Mar-Apr;12(2):169-78. doi: 10.1093/humupd/dmi046. Epub 2005 Nov 16.
• Background Sitruk-Ware R. Pharmacological profile of progestins. Maturitas. 2008 Sep-Oct;61(1-2):151-7. doi: 10.1016/j.maturitas.2008.11.011.
• Background Heikinheimo O, Ranta S, Moo-Young A, Lahteenmaki P, Gordon K. Parenteral administration of progestin Nestorone to lactating cynomolgus monkeys: an ideal hormonal contraceptive at lactation? Hum Reprod. 1999 Aug;14(8):1993-7. doi: 10.1093/humrep/14.8.1993.
• Background Heikinheimo O, Noe G, Haukkamaa M, Lahteenmaki P. The progestin ST 1435--rapid metabolism in man. Contraception. 1994 Sep;50(3):275-89. doi: 10.1016/0010-7824(94)90073-6.
• Background Kumar N, Koide SS, Tsong Y, Sundaram K. Nestorone: a progestin with a unique pharmacological profile. Steroids. 2000 Oct-Nov;65(10-11):629-36. doi: 10.1016/s0039-128x(00)00119-7.
• Background Kumar N, Fagart J, Liere P, Mitchell SJ, Knibb AR, Petit-Topin I, Rame M, El-Etr M, Schumacher M, Lambert JJ, Rafestin-Oblin ME, Sitruk-Ware R. Nestorone(R) as a Novel Progestin for Nonoral Contraception: Structure-Activity Relationships and Brain Metabolism Studies. Endocrinology. 2017 Jan 1;158(1):170-182. doi: 10.1210/en.2016-1426.
• Background Haukkamaa M, Laurikka-Routti M, Heikinheimo O, Moo-Young A. Contraception with subdermal implants releasing the progestin ST-1435: a dose-finding study. Contraception. 1992 Jan;45(1):49-55. doi: 10.1016/0010-7824(92)90140-o.
• Background Fraser IS, Weisberg E, Brache V, Alvarez F, Massai R, Mishell DR Jr, Apter D, Gale J, Tsong YY, Sivin I. Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen. Contraception. 2005 Jul;72(1):40-5. doi: 10.1016/j.contraception.2004.12.015.
• Background Sivin I, Mishell DR Jr, Alvarez F, Brache V, Elomaa K, Lahteenmaki P, Massai R, Miranda P, Croxatto H, Dean C, Small M, Nash H, Jackanicz TM. Contraceptive vaginal rings releasing Nestorone and ethinylestradiol: a 1-year dose-finding trial. Contraception. 2005 Feb;71(2):122-9. doi: 10.1016/j.contraception.2004.08.010.
• Background Weisberg E, Brache V, Alvarez F, Massai R, Mishell DR Jr, Apter D, Gale J, Sivin I, Tsong YY, Fraser IS. Clinical performance and menstrual bleeding patterns with three dosage combinations of a Nestorone progestogen/ethinyl estradiol contraceptive vaginal ring used on a bleeding-signaled regimen. Contraception. 2005 Jul;72(1):46-52. doi: 10.1016/j.contraception.2004.12.014.
• Background Rad M, Kluft C, Menard J, Burggraaf J, de Kam ML, Meijer P, Sivin I, Sitruk-Ware RL. Comparative effects of a contraceptive vaginal ring delivering a nonandrogenic progestin and continuous ethinyl estradiol and a combined oral contraceptive containing levonorgestrel on hemostasis variables. Am J Obstet Gynecol. 2006 Jul;195(1):72-7. doi: 10.1016/j.ajog.2005.12.007. Epub 2006 Mar 20.
• Background Kluft C, Meijer P, LaGuardia KD, Fisher AC. Comparison of a transdermal contraceptive patch vs. oral contraceptives on hemostasis variables. Contraception. 2008 Feb;77(2):77-83. doi: 10.1016/j.contraception.2007.10.004. Epub 2008 Jan 11.
• Background Mashchak CA, Lobo RA, Dozono-Takano R, Eggena P, Nakamura RM, Brenner PF, Mishell DR Jr. Comparison of pharmacodynamic properties of various estrogen formulations. Am J Obstet Gynecol. 1982 Nov 1;144(5):511-8. doi: 10.1016/0002-9378(82)90218-6.
• Background Marty JP, James M, Hajo N, Wepierre J Percutaneous absorption of oestradiol and progesterone: Pharmacokinetic studies. In P Mauvais-Jarvis, CFH Vickers, J Wepierre (Eds), Percutaneous absorption of steroids. London: Academic Press Inc. (London) Ltd. 1980.
• Background Timmer CJ, Mulders TM. Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. Clin Pharmacokinet. 2000 Sep;39(3):233-42. doi: 10.2165/00003088-200039030-00005.
• Background Jensen JT, Burke AE, Barnhart KT, Tillotson C, Messerle-Forbes M, Peters D. Effects of switching from oral to transdermal or transvaginal contraception on markers of thrombosis. Contraception. 2008 Dec;78(6):451-8. doi: 10.1016/j.contraception.2008.07.004. Epub 2008 Aug 28.
• Background Sitruk-Ware R, Plu-Bureau G, Menard J, Conard J, Kumar S, Thalabard JC, Tokay B, Bouchard P. Effects of oral and transvaginal ethinyl estradiol on hemostatic factors and hepatic proteins in a randomized, crossover study. J Clin Endocrinol Metab. 2007 Jun;92(6):2074-9. doi: 10.1210/jc.2007-0026. Epub 2007 Mar 20.
• Background Brache V, Mishell DR, Lahteenmaki P, Alvarez F, Elomaa K, Jackanicz T, Faundes A. Ovarian function during use of vaginal rings delivering three different doses of Nestorone. Contraception. 2001 May;63(5):257-61. doi: 10.1016/s0010-7824(01)00199-8.
• Background Odlind V, Lithell H, Selinus I, Vessby B. Unaltered lipoprotein and carbohydrate metabolism during treatment with contraceptive subdermal implants containing ST-1435. Ups J Med Sci. 1984;89(2):151-8. doi: 10.3109/03009738409178475.
• Background Goebelsmann U, Mashchak CA, Mishell DR Jr. Comparison of hepatic impact of oral and vaginal administration of ethinyl estradiol. Am J Obstet Gynecol. 1985 Apr 1;151(7):868-77. doi: 10.1016/0002-9378(85)90664-7.
• Background Protocol 330. Clinical Study Report on File. Population Council, New York, NY.
• Background Archer DF, Jensen JT, Johnson JV, Borisute H, Grubb GS, Constantine GD. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraception. 2006 Dec;74(6):439-45. doi: 10.1016/j.contraception.2006.07.005. Epub 2006 Sep 18.
• Background Scarabin PY, Oger E, Plu-Bureau G; EStrogen and THromboEmbolism Risk Study Group. Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet. 2003 Aug 9;362(9382):428-32. doi: 10.1016/S0140-6736(03)14066-4.
• Background Belsey EM, Machin D, d'Arcangues C. The analysis of vaginal bleeding patterns induced by fertility regulating methods. World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction. Contraception. 1986 Sep;34(3):253-60. doi: 10.1016/0010-7824(86)90006-5.
• Background Merkatz RB, Plagianos M, Hoskin E, Cooney M, Hewett PC, Mensch BS. Acceptability of the Nestorone(R)/ethinyl estradiol contraceptive vaginal ring: development of a model; implications for introduction. Contraception. 2014 Nov;90(5):514-21. doi: 10.1016/j.contraception.2014.05.015. Epub 2014 Jun 2.
• Background Isidori AM, Pozza C, Esposito K, Giugliano D, Morano S, Vignozzi L, Corona G, Lenzi A, Jannini EA. Development and validation of a 6-item version of the female sexual function index (FSFI) as a diagnostic tool for female sexual dysfunction. J Sex Med. 2010 Mar;7(3):1139-46. doi: 10.1111/j.1743-6109.2009.01635.x. Epub 2009 Dec 1.
• Background Borch KH, Braekkan SK, Mathiesen EB, Njolstad I, Wilsgaard T, Stormer J, Hansen JB. Anthropometric measures of obesity and risk of venous thromboembolism: the Tromso study. Arterioscler Thromb Vasc Biol. 2010 Jan;30(1):121-7. doi: 10.1161/ATVBAHA.109.188920. Epub 2009 Oct 15.
• Background Pomp ER, le Cessie S, Rosendaal FR, Doggen CJ. Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations. Br J Haematol. 2007 Oct;139(2):289-96. doi: 10.1111/j.1365-2141.2007.06780.x.
• Background Simmons KB, Kumar N, Plagianos M, Roberts K, Hoskin E, Han L, Alami M, Creasy G, Variano B, Merkatz R. Effects of concurrent vaginal miconazole treatment on the absorption and exposure of Nestorone(R) (segesterone acetate) and ethinyl estradiol delivered from a contraceptive vaginal ring: a randomized, crossover drug-drug interaction study. Contraception. 2018 Mar;97(3):270-276. doi: 10.1016/j.contraception.2017.10.010. Epub 2017 Oct 31.

Drugs

Indications

No indication recorded.