Phase I/II pharmacokinetic and pharmacodynamic evaluation of two levonorgestrel-only contraceptive patches in a multicenter randomized trial

Carolyn L. Westhoff, Beatrice A. Chen, Jeffrey T. Jensen, Kurt Barnhart, Michael Thomas, Stephanie Teal, Diana Blithe

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Objectives: To evaluate the pharmacokinetic and pharmacodynamic effects of two novel levonorgestrel (LNG)-only contraceptive patches. Study Design: This multi-center Phase I/II trial randomized participants to use a 7-day transdermal patch designed to deliver a 40 mcg or 75 mcg daily LNG dose for 11 consecutive weeks; randomization was stratified by body mass index (BMI) <32 or 32–40 kg/m 2 . Evaluations occurred twice weekly for 5 weeks, then once weekly with supplemental visits for participants reporting a urinary LH surge. We evaluated pharmacokinetics via the weekly trough serum LNG concentrations (≥180 pg/mL considered therapeutic). The primary pharmacodynamic outcomes were cervical mucus and ovulation, evaluated using modified Insler cervical mucus scores and serum markers of ovulation. Results: Randomization yielded similar groups. Of 121 enrolled women, 117 contributed analyzable data. Overall, mean LNG concentrations achieved with use of the 75 mcg patch [value] were roughly double those seen with the 40 mcg dose. Concentrations achieved in higher-BMI women (BMI=32–40 kg/m 2 ) were 50% lower compared to lower-BMI women for both patches. During the study, 94/117 (80%) participants had at least one LNG concentration <180 pg/mL. Insler scores were ≥5 at least once in 102/117 (87%) of participants, and ovulation occurred at least once in 81/117 (69%). Sixty participants (51%) had at least one ovulation following an Insler score ≥5; this occurred most frequently among higher-BMI participants using the lower-dose patch (19/25, 76%). Conclusions: Women using two investigational LNG patches did not achieve consistent concentrations of LNG >180 pg/mL, an efficacy benchmark established in other studies with LNG implants, and they experienced high rates of ovulation as well as cervical mucus scores not supportive of high contraceptive efficacy. Implications: The novel LNG-only patches in this study may not adequately decrease pregnancy risk, particularly for higher-BMI women. Future studies of LNG-only contraceptive patches will need to employ higher LNG doses and assess the acceptability and safety of such dosing.

Original languageEnglish (US)
Pages (from-to)151-157
Number of pages7
JournalContraception
Volume98
Issue number2
DOIs
StatePublished - Aug 2018

Keywords

  • Cervical mucus
  • Contraceptive patch
  • Levonorgestrel
  • Ovulation suppression
  • Pharmacodynamics

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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