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 T Ackerman; Lisa Flood; Joseph A Chiodo 3rd; Elizabeth Io Garner; SECURE Investigators

doi:10.1016/j.contraception.2020.11.011

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

Contraception. 2021 Mar;103(3):137-143. doi: 10.1016/j.contraception.2020.11.011. Epub 2020 Nov 28.

Authors

Affiliations

¹ Essential Access Health, Los Angeles, CA, USA. Electronic address: AnitaLNelson1@gmail.com.
² University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA.
³ University of Washington, Seattle Women's Health, Research, Gynecology, Seattle, WA, USA.
⁴ George Washington University School of Medicine, Washington, DC, USA.
⁵ Advances In Health, Inc., Houston, TX, USA.
⁶ Columbia University Irving Medical Center, New York, NY, USA.
⁷ Comprehensive Clinical Trials LLC, West Palm Beach, FL, USA.
⁸ ALK-Abello, Inc. Pharmaceuticals, Bedminster, NJ, USA.
⁹ Agile Therapeutics, Inc., Princeton, NJ, USA.
¹⁰ ObsEva, One Financial Center, Boston, MA, USA.

PMID: 33259782
DOI: 10.1016/j.contraception.2020.11.011

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.

Trial registration: ClinicalTrials.gov NCT02158572.

Keywords: Combination hormonal contraceptive; Contraceptive patch; Ethinyl estradiol; Levonorgestrel; Phase 3 trial; Transdermal.

Publication types

Clinical Trial, Phase III
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Body Mass Index
Contraceptives, Oral, Combined*
Estradiol
Ethinyl Estradiol / adverse effects
Female
Humans
Levonorgestrel* / adverse effects
Pregnancy

Substances

Contraceptives, Oral, Combined
Ethinyl Estradiol
Estradiol
Levonorgestrel

Associated data

ClinicalTrials.gov/NCT02158572