Safety, Tolerability, and Pharmacokinetics of Single and Multiple Topical Applications of Sodium Taurodeoxycholate, a Treatment for Atopic Dermatitis

Abstract

ABSTRACT Sodium taurodeoxycholate (TDCA) gel is a novel candidate for the treatment of atopic dermatitis and is currently under clinical development. TDCA is a taurine‐conjugated bile acid derivative that acts as a G protein‐coupled bile acid receptor agonist and modulates immune responses. This phase 1 study aimed to investigate the safety, tolerability, and pharmacokinetic profile of sodium TDCA after single and multiple topical administrations of sodium TDCA gel in healthy male subjects. Subjects were randomized to receive a single topical administration of sodium TDCA 5, 10, 30, and 50 mg (0.05%, 0.1%, 0.3%, and 0.5% of 10 g) gel or placebo in the single‐ascending dose (SAD) study (N = 32), and sodium TDCA 10, 30, and 50 mg (0.1%, 0.3%, and 0.5% of 10 g) gel or placebo for 28 days (N = 24) in the multiple‐ascending dose (MAD) study. Safety profiles were assessed based on adverse events (AEs), global irritation score (GIS), and numerical pain rating scale (NPRS). Serial blood samples were collected for 24 h at baseline and up to 168 h post‐dose in the SAD study and for 72 h at baseline and up to 240 h post‐dose at steady state in the MAD study. No serious AEs were reported and all AEs were mild in severity for both SAD and MAD studies. The plasma concentrations of TDCA did not increase significantly after topical administrations. Changes in the plasma concentrations of TDCA likely reflected the circadian rhythm rather than the administration of sodium TDCA gel.

Keywords

• pharmacokinetics
• phase 1
• safety