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

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.