Ethinyl estradiol and levonorgestrel pharmacokinetics with a low-dose transdermal contraceptive delivery system, AG200-15: a randomized controlled trial

Background: This study evaluated the ethinyl estradiol (EE) and levonorgestrel (LNG) pharmacokinetic profiles of AG200-15, a transdermal contraceptive delivery system, compared with a combination oral contraceptive (COC) containing EE 35 mcg and norgestimate 250 mcg. Study design: A Phase 1, open-label, single-center study in 36 healthy women was conducted over three cycles with a randomized crossover design. After a run-in cycle of 21 days on and 7 days off with AG200-15, participants were randomized to receive one of two treatments: a 21/7-day cycle of AG200-15 either followed or preceded by one cycle of the COC. This trial is registered on ClinicalTrials.gov under the identifier NCT01243580. Results: During the third week of AG200-15 use, mean (+/- standard deviation) maximum serum concentration (C,), area under the curve(0-168 h) and steady-state concentration (Css48-168 h) for EE were 51.3 +/- 17.3 pg/mL, 6.26 +/- 2.46 ng h/mL and 35.7 +/- 14.5 pg/mL, respectively; for LNG, the corresponding values were 2400 +/- 1140 pg/mL, 317 +/- 159 ng h/mL and 1847 +/- 930 pg/mL, respectively. The AG200-15 EE C-max was approximately 60% lower and the EE C-ss was 15%-20% lower than those obtained with the COC. The calculated daily dose of AG200-15 was equivalent to a 30-mcg EE COC. The most common adverse events (AEs; >10%) in the AG200-15 group were headache, nausea and application-site irritation. All drug-related AEs were mild, and no serious AEs were reported. Conclusions: EE and LNG daily exposure during AG200-15 treatment was within the range reported for a low-dose COC. The daily EE dose with AG 200-15 was equivalent to a 30-mcg COC and was safe and well tolerated. (C) 2012 Elsevier Inc. All rights reserved.