Efficacy, Safety, and Tolerability of a Levonorgestrel/Ethinyl Estradiol Transdermal Delivery System: Phase 3 Clinical Trial Results.

Abstract Objective To assess the contraceptive efficacy, safety, and tolerability of a contraceptive transdermal delivery system, (TDS; TWIRLA®) 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 (three 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 18–35 years, excluding cycles without intercourse or when other contraceptive methods were used. Results The study enrolled 2,032 demographically diverse women in the US, of which 35.3% had a BMI ≥30 kg/m2. In the primary efficacy analysis, the PI (95% CI) 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 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/m2. The TDS safety and tolerability profile was consistent with other similar dose combined hormonal contraceptives. Results of this phase 3 study supported the FDA approval of TWIRLA® for prevention of pregnancy in women with BMI