A phase I study of TAS‐205 in patients with Duchenne muscular dystrophy

Abstract

Abstract Objective 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 D 2 (PGD 2 ), might have a role in DMD pathology. We therefore investigated the safety, pharmacokinetics (PK), and pharmacodynamics of a highly selective HPGDS inhibitor (TAS‐205) in Japanese patients with genetically confirmed DMD. Methods 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 PGD 2 metabolites was also assessed. Results 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. Interpretation We confirmed the safety and tolerability of TAS‐205 in this study. TAS‐205 decreased the total urinary excretion of PGD 2 metabolites in a dose‐dependent manner, suggesting that TAS‐205 might be a therapeutic option to treat DMD patients.