Local Transdermal Delivery of Telapristone Acetate Through Breast Skin, Compared With Oral Treatment: A Randomized Double-Blind, Placebo-Controlled Phase II Trial

Oukseub Lee, Melissa Pilewskie, Scott Karlan, Mary B. Tull, Kelly Benante, Yanfei Xu, Luis Blanco, Irene Helenowski, Masha Kocherginsky, Shivangi Yadav, Omid Hosseini, Nora M Hansen, Kevin P Bethke, Miguel Muzzio, Melissa A. Troester, Eileen Dimond, Marjorie Perloff, Brandy Heckman-Stoddard, Seema A. Khan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Oral breast cancer prevention medications entail systemic exposure, limiting acceptance by high-risk women. Delivery through the breast skin, although an attractive alternative, requires demonstration of drug distribution throughout the breast. We conducted a randomized double-blind, placebo-controlled phase II clinical trial comparing telapristone acetate, a progesterone receptor antagonist, administered orally (12 mg/day) or transdermally (12 mg/breast) for 4 ± 1 weeks to women planning mastectomy. Plasma and tissue concentrations, measured at five locations in the mastectomy specimen using liquid chromatography tandem mass spectrometry were compared. In 60 evaluable subjects, median drug concentration (ng/g tissue) was 103 (interquartile range (IQR): 46.3–336) in the oral vs. 2.82 (IQR: 1.4–5.5) in the transdermal group. Despite poor dermal permeation, within-breast drug distribution pattern was identical in both groups (R2 = 0.88, P = 0.006), demonstrating that transdermally and orally delivered drug is distributed similarly through the breast, and is strongly influenced by tissue adiposity (P < 0.0001). Other skin-penetrant drugs should be tested for breast cancer prevention.

Original languageEnglish (US)
JournalClinical pharmacology and therapeutics
DOIs
StateAccepted/In press - 2020

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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