New patch options Could they catch on?
When the Ortho Evra transdermal contraceptive (Ortho Women's Health & Urology, Raritan, NJ) was introduced in 2002, use of the patch caught on quickly with young women. However, pharmacokinetic data indicated the release of ethinyl estradiol (EE) from the first-generation patch was associated with substantially higher area under the curve for EE than low-dose contraceptives.1-4
Research is investigating two new contraceptive patch options. One patch under development delivers a low dose of estrogen in combination with levonorgestrel, and is applied once weekly for three weeks, followed by a patch-free week. The second option is a low-dose, progestin-only contraceptive patch designed to provide an option for women for who estrogen-containing contraceptives are contraindicated, inappropriate, or unwanted. Agile Therapeutics of Princeton, NJ, is developing both patches.
The high estrogen impact of the first generation Evra patch, the related warning added to the patch package label, and highly publicized reports of cardiovascular events with patch users all resulted in a "boom bust" phenomenon, observes Andrew Kaunitz, MD, professor and associate chair in the Department of Obstetrics And Gynecology at the University of Florida College of Medicine – Jacksonville. After initial rapid uptake of the patch, use of the contraceptive option rapidly lost popularity among U.S. women. "From this perspective, a lower estrogen transdermal contraceptive would be a most welcome addition to the cafeteria of contraceptive choices we offer our patients," says Kaunitz.
Research now emerges
Agile Therapeutics' AG200-15 is a weekly combination hormonal contraceptive patch containing the active ingredients levonorgestrel (LNG) and ethinyl estradiol (EE), both of which have a well-established history of efficacy and safety in combination contraceptives, says Marie Foegh, MD, the company's chief medical officer and vice president of clinical research and development. The patch is applied once weekly for three weeks, followed by a fourth patch-free week.
Results of a pivotal pharmacokinetic study presented at the 2010 annual meeting of the American Society of Reproductive Medicine indicate the low daily dose of EE delivered by the AG200-15 patch was comparable to a low-dose oral contraceptive at 30 mcg per day.5
Agile has completed enrollment in the two pivotal Phase 3 trials for AG200-15, according to Foegh. Recruiting and enrollment of patients began in August 2010, with more than 1,500 women enrolled in just eight weeks, she notes. "This rapid enrollment exceeded expectations and has been attributed to the interest among patients in the option of a patch for contraception," says Foegh. "The study will be completed in the fourth quarter of 2011. It is our goal to submit the NDA [new drug application] in the first quarter of 2012."
What is the research status of the low-dose, progestin-only contraceptive patch? Known as AG900, the patch delivers a controlled dose of levonorgestrel. The regimen is continuous, with women replacing the patch every seven days with no "patch-free" period, says Foegh. The delivery of the drug eliminates some of the challenges associated with progestin-only options, says Foegh.
Clinical trials are being conducted through a clinical trial agreement with the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. A key pharmacokinetic and pharmacodynamic study has been initiated, and enrollment is ongoing, she states.
Look for more information on patch development. AG200-15 data will be presented in two posters at the upcoming American College of Obstetrics and Gynecology 2011 Annual Meeting in Washington, DC, April 30-May 4. (Look for further coverage in an upcoming issue of Contraceptive Technology Update.)
Data from AG200-15 clinical trials has been presented at various medical meetings, says Foegh. Full publications of these studies are in process, with the first manuscript now in press in the Journal of Hormone Molecular Biology and Clinical Investigation, she states.
References
- Jick SS, Kaye JA, Russmann S, et al. Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 mcg of ethinyl estradiol. Contraception 2006; 73:223-228.
- Cole JA, Norman H, Doherty M, et al. Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users. Obstet Gynecol 2007;109(2 Pt 1):339-346.
- Boston Collaborative Drug Surveillance Program. Postmarketing study of ORTHO EVRA and levonorgestrel oral contraceptives containing hormonal contraceptives with 30 μg of EE in relation to non-fatal venous thromboembolism, ischemic stroke and myocardial infarction. Accessed at: http://www.clinicaltrials.gov/ct2/show/NCT00511784.
- Jick S, Kaye JA, Li L, et al. Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception 2007;76:4-7.
- Archer DF, Stanczyk FZ, Rubin A, et al. Evaluation of exposure to ethinyl estradiol (EE) with a low-dose combination transdermal contraceptive delivery system (AG200-15) compared to low-dose combination oral contraceptive. Presented at the 2010 American Society of Reproductive Medicine. Denver; October 2010.
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