Low-Dose Levonorgestrel and Ethinyl Estradiol Patch and Pill: A Randomized Controlled Trial

Kaunitz, Andrew M. MD; Portman, David MD; Westhoff, Carolyn L. MD; Archer, David F. MD; Mishell, Daniel R. Jr MD; Rubin, Arkady PhD; Foegh, Marie MD

Obstetrics & Gynecology:
doi: 10.1097/AOG.0000000000000095
Contents: Original Research
Abstract

OBJECTIVE: To compare a new low-dose levonorgestrel and ethinyl estradiol contraceptive patch (Patch) with a combination oral contraceptive (Pill; 100 micrograms levonorgestrel, 20 micrograms ethinyl estradiol) regarding efficacy, safety, compliance, and unscheduled uterine bleeding.

METHODS: Women (17–40 years; body mass index 16–60) were randomized in a 3:1 ratio to one of two groups: Patch only (13 cycles) or Pill (six cycles) followed by Patch (seven cycles). Investigators evaluated adverse events during cycles 2, 4, 6, 9, and 13. Participants recorded drug administration and uterine bleeding on daily diary cards. Compliance was assessed by measuring levonorgestrel and ethinyl estradiol plasma levels. Pearl Index (pregnancies per 100 woman-years) was calculated to evaluate efficacy.

RESULTS: Participants (N=1,504) were randomized to Patch (n=1,129) or Pill (n=375). Approximately 30% were obese, more than 40% were racial or ethnic minorities, and more than 55% were new users of hormonal contraceptives. Laboratory-verified noncompliance (undetectable plasma drug levels) was 11% of Patch and 12.6% of Pill users at cycle 6. Pearl Indices (95% confidence intervals) for the intention-to-treat population (cycles 1–6) were 4.45 (2.34–6.57) for Patch and 4.02 (0.50–7.53) for Pill; excluding laboratory-verified noncompliant participants, Pearl Indices were 2.82 (0.98–4.67) for Patch and 3.80 (0.08–7.52) for Pill (differences not statistically significant). Incidence of unscheduled bleeding and incidence and severity of adverse events were similar for both contraceptives (no statistically significant difference).

CONCLUSIONS: Efficacy and safety of the new contraceptive Patch are comparable to those of a Pill. Laboratory-verified noncompliance and bleeding profile are similar between the two treatments. The Patch was well tolerated.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01181479.

LEVEL OF EVIDENCE: I

In Brief

Contraceptive efficacy and compliance between a new low-dose levonorgestrel and ethinyl estradiol patch and pill are comparable.

Author Information

Department of Obstetrics and Gynecology, University of Florida College of Medicine, Jacksonville, Florida; the Columbus Center for Women's Health Research, Columbus, Ohio; Mailman School of Public Health, Columbia University, New York, New York; the Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, Virginia; the Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California; ARSTAT, Flemington, New Jersey; and Agile Therapeutics, Inc, Princeton, New Jersey.

Corresponding author: Andrew M. Kaunitz, MD, Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville, 653-1 West 8th Street, Jacksonville, FL 32209; e-mail: andrew.kaunitz@jax.ufl.edu.

Portions of this manuscript were presented as a poster at both the 60th and 61st Annual Meetings of the American Congress of Obstetricians and Gynecologists, May 5–9, 2012, San Diego, California, and May 4–8, 2013, New Orleans, Louisiana.

Financial Disclosure Dr. Kaunitz is a consultant to Actavis, Bayer Healthcare, Merck, and Teva; his academic department (Department of Obstetrics & Gynecology, University of Florida College of Medicine–Jacksonville) receives financial support to conduct clinical trials from Agile Therapeutics, Inc, Bayer Healthcare, and Teva. Dr. Portman has received research grants from Agile Therapeutics, Inc, Bayer Healthcare, Teva, Warner Chilcott, Actavis, Merck, and Population Council; is a consultant to Teva and Actavis; and serves on the speakers' bureau for Teva and Warner Chilcott. Dr. Westhoff is a consultant to Bayer, Merck, Actavis, and Agile. Dr. Archer is a consultant to Abbot Laboratories, Agile Therapeutics, Inc, Bayer Healthcare, CHEMO, Endoceutics, Ferring Pharmaceuticals, HRA Pharma, Merck, Shionogi, Teva Women's Healthcare, Warner Chilcott, and Watson Pharmaceutical; has received research support from Abbott Laboratories, Bayer Healthcare, Endoceutics, Merck, Pfizer, Warner Chilcott, and Watson Pharmaceutical; and has received industry honoraria from Bayer Healthcare, Besins, and Merck. Dr. Mishell is a consultant to Agile Therapeutics, Inc. Dr. Rubin is a consultant to Agile Therapeutics, Inc. Dr. Foegh is an employee of Agile Therapeutics, Inc and has stock holdings in the company. Editorial assistance was provided by Phase Five Communications Inc, with financial support provided by Agile Therapeutics, Inc.

© 2014 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.