Efficacy, safety, and tolerability of a levonorgestrel/ethinyl estradiol transdermal delivery system: Phase 3 clinical trial results
Anita L. Nelson, Andrew M. Kaunitz, Robin Kroll, James A. Simon, Alfred N. Poindexter, Paula M. Castaño, Ronald Ackerman, Lisa Flood, Joseph Chiodo, Elizabeth Garner
Abstract
ObjectiveTo assess the contraceptive efficacy, safety, and tolerability of a contraceptive transdermal delivery system, (TDS; TWIRLAⓇ) containing levonorgestrel (LNG) and ethinyl estradiol (EE).Study designThis single-arm, open-label, multicenter, 1-year (13 cycle), phase 3 study enrolled sexually active women ≥18 years old at risk for pregnancy irrespective of body mass index (BMI). Women used patches in 28-day cycles (3 consecutive administrations of 7-day patches followed by 7 days off-treatment/patch-free week). We assessed contraceptive efficacy by the Pearl Index (PI) in women 18 to 35 years, excluding cycles without intercourse or when other contraceptive methods were used.ResultsThe study enrolled 2032 demographically diverse women in the US, of which 35.3% had a BMI ≥30 kg/m2. In the primary efficacy analysis, the PI (95% confidence interval) was 5.8 (4.5–7.2) pregnancies per 100 woman-years. PIs trended higher as BMI increased; the PI was 4.3 (2.9–5.8) in women with BMI <30 kg/m2 and 8.6 (5.8–11.5) in women with BMI ≥30 kg/m2. Hormone-related treatment-emergent adverse events included nausea (4.1%) and headache (3.6%); 11% of women discontinued due to adverse events. Four women (all with BMIs ≥30 kg/m2) reported thromboembolic events considered related to treatment.ConclusionsThe low-dose LNG/EE TDS was effective in preventing pregnancy in a population of women representative of US demographics. Efficacy was reduced in women with BMI ≥30 kg/m2. The TDS safety and tolerability profile was consistent with other similar dose combined hormonal contraceptives. Results of this phase 3 study supported the US Food and Drug Administration approval of TWIRLAⓇ for prevention of pregnancy in women with BMI <30 kg/m2.ImplicationsTDS (120 µg/day levonorgestrel and 30 µg/day ethinyl estradiol) is an effective, low-dose transdermal contraceptive patch with favorable tolerability profile approved for prevention of pregnancy in women with BMI <30 kg/m2. TDS has reduced effectiveness in women with BMI ≥30 kg/m2.