Efficacy, safety, and tolerability of a levonorgestrel/ethinyl estradiol transdermal delivery system: Phase 3 clinical trial results

Objective: To assess the contraceptive efficacy, safety, and tolerability of a contraceptive transdermal delivery system, (TDS; TWIRLA (R)) containing levonorgestrel (LNG) and ethinyl estradiol (EE). Study design: This 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 offtreatment/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. Results: The study enrolled 2032 demographically diverse women in the US, of which 35.3% had a BMI >= 30 kg/m(2) . 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/m(2) and 8.6 (5.8-11.5) in women with BMI >= 30 kg/m(2) . 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/m(2)) reported thromboembolic events considered related to treatment. Conclusions: The 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/m(2). 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 (R) for prevention of pregnancy in women with BMI <30 kg/m(2). (C) 2020 The Authors. Published by Elsevier Inc.