Publication: CTS – Clinical and Translational Science

Co-Authored by: Yanick Botilde, Consultant Clinical Pharmacokinetics and Laure Viguerie, Clinical Consultant Pharmacokinetics

Summary

BI 1839100 is a selective TRPA1 antagonist being investigated for its potential in treating conditions involving TRPA1 activation, such as pain, skin, and lung disorders. In this first-in-human phase I study, preclinical in vitro and in vivo models showed that BI 1839100 reduced AITC-induced TRPA1 activation. In healthy male volunteers, single doses up to 300 mg were safe, showed dose-proportional pharmacokinetics, and demonstrated dose-dependent inhibition of dermal blood flow in an AITC skin challenge model—confirming target engagement and pharmacological activity. These findings support further clinical development and validate the AITC skin challenge as a method for early TRPA1 inhibitor testing.

Key Points:

• Target & Rationale: BI 1839100 selectively inhibits TRPA1, a receptor involved in pain, skin, and lung disorders.
• Preclinical Findings: Reduced AITC-induced Ca²⁺ increase in TRPA1-overexpressing cells and decreased skin edema in mice.
• Clinical Safety: Single doses up to 300 mg were well-tolerated with no adverse event imbalance versus placebo.
• Pharmacokinetics: Dose-proportional exposure observed between 40–300 mg.
• Pharmacodynamics: Dose-dependent inhibition of AITC-induced dermal blood flow confirmed TRPA1 target engagement.

Access Full Article: Proof of Pharmacology, Safety, and Pharmacokinetics of the Novel TRPA1 Antagonist BI 1839100: A Randomized, Placebo-Controlled, Parallel Group, First-In-Human Study in Healthy Male Participants