A phase I study of TAS-205 in patients with DMD

Currently, the only approved standard Duchenne muscular dystrophy (DMD) treatment in Japan is oral steroids, which have various disadvantages. Previous work has suggested that hematopoietic-type prostaglandin D synthase (HPGDS), involved in production of the inflammatory mediator prostaglandin D2 (PGD2), might have a role in DMD pathology. Authors therefore investigated the safety, pharmacokinetics (PK), and pharmacodynamics of a highly selective HPGDS inhibitor (TAS-205) in Japanese patients with genetically confirmed DMD.

This was a double-blind, randomized, placebo-controlled phase I study to evaluate the use of single or 7-day repeated doses of TAS-205 administered orally. The urinary excretion of PGD2 metabolites was also assessed.

The PK analysis set included 15 and 14 patients in the single- and repeated-dose periods, respectively; the pharmacodynamics set and the safety set included 21 and 19 patients in each period, respectively. The PK of TAS-205 were linear in the dose range studied (1.67-13.33 mg/kg/dose) and the plasma concentration of TAS-205 reached steady state by Day 4. TAS-205 dose-dependently decreased the urinary excretion of tetranor-prostaglandin D metabolite at each measurement time point and did not affect the urinary excretion of tetranor-prostaglandin E metabolite. No clinically significant adverse events were reported after TAS-205 single or repeated administration.

The researchers confirmed the safety and tolerability of TAS-205 in this study. TAS-205 decreased the total urinary excretion of PGD2 metabolites in a dose-dependent manner, suggesting that TAS-205 might be a therapeutic option to treat DMD patients.


A phase I study of TAS-205 in patients with Duchenne muscular dystrophy. Takeshita E, Komaki H, Shimizu-Motohashi Y, Ishiyama A, Sasaki M, Takeda S. Ann Clin Transl Neurol., 2018 (Oct).


OnClinicaltrials.gov : NCT02246478 and NCT02752048