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 (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. RESULTS: The 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. 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 US Food and Drug Administration approval of TWIRLAⓇ for prevention of pregnancy in women with BMI <30 kg/m2. IMPLICATIONS TDS (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.