TAR-0520, a new candidate in oncodermatology: Results of a phase 1 program in healthy volunteers

TAR-0520 gel is a new topical formulation of brimonidine tartrate designed to prevent chemotherapy-induced skin toxicities. We report here the main outcomes of the phase 1 program which included two double-blind, randomized trials in healthy volunteers (TAR006 and TAR012) and were performed to evaluate the safety, local tolerability, pharmacokinetics, and pharmacodynamics (PD) of TAR-0520 gel.

In TAR006, participants received four concentrations of TAR-0520 gel (0.5%, 0.75%, 1% and 1.5% of Brimonidine tartrate), placebo, or active comparator (Mirvaso® Galderma International, France) applied daily to the chest for 21 days, while TAR012 evaluated TAR-0520 gel 1% and 1.5% on the chest and face over the same duration. Local tolerance was assessed daily in both studies using mean cumulative irritation index and maximum irritation score as key endpoints. Skin blanching was assessed via chromameter-measured reductions in skin redness as a marker of vasoconstriction and product potency. In TAR006, systemic exposure to brimonidine tartrate was assessed from blood samples collected in a separate cohort treated with TAR-0520 gel 1%.

Overall, 28 participants were randomized in TAR006 and 26 were randomized in TAR012. Both studies showed excellent local tolerance with 50 healthy volunteers reporting no evidence of irritation with any treatment and four patients reporting barely perceptible minimal erythema. No adverse events related to TAR-0520 gel were reported. Minimal systemic absorption was observed that was not considered to be clinically relevant. PD studies indicated dose-dependent vasoconstriction with once-daily use lasting over 24 h.

Under the conditions of these studies, TAR-0520 gel presents a very favorable safety profile with little to no local irritation and insignificant systemic exposure. Allowing a superficial skin vasoconstriction over a period of 24 h, it offers a safe, patient-friendly, and adaptable topical solution. The 1.5% concentration was selected for further development and phase II trials for managing chemotherapy-related skin toxicities are in progress.

- TARIAN 006, 2023-504178-39-00 approved 24/08/203. - TARIAN 012, 2324CMCL096 approved 28/05/2024.