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 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. ✩ Clinical trial registration: This clinical trial was registered at www.ClinicalTrials. gov as: NCT02158572; Efficacy, Safety and Tolerability Study of Agile AG200-15 Transdermal Contraceptive Delivery System. The URL can be found at: https:// clinicaltrials.gov/ct2/show/NCT02158572. ✩✩ Funding: This study was funded by Agile Therapeutics, Inc., Princeton, NJ. Medical writing was provided by PharmaWrite, LLC, and was funded by Agile Therapeutics, Inc. Agile Therapeutics, Inc. provided a full review of the article and had a role in the design, execution, data collection and analysis, reporting, and funding of the study. ★ 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/m 2. TDS has reduced effectiveness in women with BMI ≥30 kg/m 2 .

Estetrol-drospirenone combination oral contraceptive: North American phase 3 efficacy and safety results

“…Very few (<1%) women discontinued due to bleeding between periods. In contrast, the proportion of women reporting unscheduled bleeding/spotting with a new EE/levonorgestrel contraceptive patch was 60% in cycle 1 and 42% in cycle 13 [36]. Complete absence of any bleeding (scheduled or unscheduled) with E4/DRSP occurred in 10% or less users per cycle, allowing most women to expect some bleeding.…”

“…Most recently, a U.S. phase 3 study with 2031 women, 35% of whom were obese, who used a new contraceptive patch with dosing equivalent to an EE 30 mcg/levonorgestrel 120 mcg oral contraceptive, four (0.2%) thrombotic events occurred (all in obese women) [36]. Thus, even with low-dose EE short-acting combination contraceptives, thrombosis risk is still elevated substantially.…”

Low Thrombin Generation in Users of a Contraceptive Containing Estetrol and Drospirenone

“…Three thrombotic events were reported among 1683 (0.2%) US women using EE 10 mcg/norethindrone acetate 1 mg, of whom 18% were obese ( 45 ). Four VTE occurred among 1188 (0.3%) US women using a vaginal ring delivering EE 13 mcg and segesterone acetate 150 mcg per day ( 46 ) and 4 VTEs occurred among 2031 (0.2%) US women, of whom 35% were obese, using a new contraceptive patch with dosing equivalent to an EE 30 mcg/levonorgestrel 120 mcg oral contraceptive pill ( 47 ). Thus, even with low-dose EE-containing CHCs, the thrombotic risk is still elevated substantially and higher than the one observed during the clinical development of E4/DRSP.…”

New Contraception Update — Annovera, Phexxi, Slynd, and Twirla

“…The contraceptive efficacy, safety, and tolerability of Twirla were evaluated in a single-arm, open-label, phase 3 study in 102 US sites [ 32• ]. Investigators enrolled 2032 participants who were 18 years and older, had regular 21 to 38 day cycles, were at risk of pregnancy, and did not have any contraindications to combined hormonal contraceptive use based on the 2016 US Medical Eligibility Criteria for Contraceptive Use.…”