Systemic Pharmacokinetics, Safety, and Preliminary Efficacy of Topical AhR Agonist Tapinarof: Results of a Phase 1 Study

Clin Pharmacol Drug Dev. 2018 Jun;7(5):524-531. doi: 10.1002/cpdd.439. Epub 2018 Feb 1.

Abstract

Tapinarof cream is a novel topical nonsteroidal agent that represents a unique class of anti-inflammatory molecules targeting the aryl hydrocarbon receptor. Study 201851 was an open-label, 2-cohort sequential study that assessed the systemic pharmacokinetics, safety, and efficacy of tapinarof in adults with moderate to severe atopic dermatitis. A total of 11 participants were enrolled: 5 received 2% cream, and 6 received 1% cream. Tapinarof was systemically absorbed, and measurable amounts were detected in both cohorts. Generally, plasma exposure was greater with the 2% cream and decreased from day 1 to day 21. Median Tmax ranged from 1 to 4 hours. Preliminary efficacy results were similar between the 1% and 2% concentrations, with the 1% cream showing better tolerability based on 3 subjects in the 2% cohort who discontinued treatment because of systemic AEs. The efficacy and safety of 1% tapinarof support results of previous positive studies that used a different formulation. However, conclusions in the present study are limited because of the open-label design and small number of participants. The 1% cream was selected as the concentration for use in future studies because of its lower AE incidence and efficacy comparable to the 2% cream.

Trial registration: ClinicalTrials.gov NCT02466152.

Keywords: AhR agonist; atopic dermatitis; systemic exposure; topical medicine.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Adult
  • Dermatitis, Atopic / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Resorcinols / administration & dosage*
  • Resorcinols / adverse effects
  • Resorcinols / pharmacokinetics*
  • Stilbenes / administration & dosage*
  • Stilbenes / adverse effects
  • Stilbenes / pharmacokinetics*
  • Treatment Outcome
  • Young Adult

Substances

  • Resorcinols
  • Stilbenes
  • tapinarof

Associated data

  • ClinicalTrials.gov/NCT02466152