BACKGROUND:DWP14012 (fexuprazan), a novel potassium-competitive acid blocker, is under development for the treatment of acid-related disorders. AIMS: To compare the pharmacodynamics (PDs), pharmacokinetics (PKs) and safety of DWP14012 among healthy subjects of Korean, Caucasian and Japanese descent. METHODS: A randomised, double-blind, placebo-controlled, single- and multiple-dose study was conducted. Ten subjects in each dose group (40, 60 or 80 mg for Koreans; 40 or 80 mg for Caucasians; 20, 40 or 80 mg for Japanese) were randomly assigned to DWP14012 or a placebo. Twenty-four-hour intragastric pH measurements and serial blood samples were collected for PK/PD evaluation. The PK/PD parameters were compared between each ethnicity. RESULTS: The extent of gastric acid suppression was similar among the ethnicities; the mean percentages of time that the intragastric pH was above 4 after multiple doses of 40 mg in the Korean, Caucasian and Japanese subjects were 64.3%, 62.8% and 70.3%, respectively, and the corresponding values for the 80 mg dose were 94.8%, 90.6% and 90.6% respectively. The changes in serum gastrin were not clinically significant between all three ethnicities. The systemic exposure of DWP14012 was similar between the three ethnicities after the 40 mg doses but slightly lower in Caucasian and Japanese subjects after the 80 mg doses. Gastric acid suppression by DWP14012 showed a clear exposure-response relationship in the three ethnicities. CONCLUSIONS:Gastric acid suppression by DWP14012 was similar among the Korean, Caucasian and Japanese subjects in this study, and the PK, PK-PD relationships and safety were also similar among the three ethnicities. DWP14012 could be used without consideration of ethnicity.
RCT Entities:
BACKGROUND: DWP14012 (fexuprazan), a novel potassium-competitive acid blocker, is under development for the treatment of acid-related disorders. AIMS: To compare the pharmacodynamics (PDs), pharmacokinetics (PKs) and safety of DWP14012 among healthy subjects of Korean, Caucasian and Japanese descent. METHODS: A randomised, double-blind, placebo-controlled, single- and multiple-dose study was conducted. Ten subjects in each dose group (40, 60 or 80 mg for Koreans; 40 or 80 mg for Caucasians; 20, 40 or 80 mg for Japanese) were randomly assigned to DWP14012 or a placebo. Twenty-four-hour intragastric pH measurements and serial blood samples were collected for PK/PD evaluation. The PK/PD parameters were compared between each ethnicity. RESULTS: The extent of gastric acid suppression was similar among the ethnicities; the mean percentages of time that the intragastric pH was above 4 after multiple doses of 40 mg in the Korean, Caucasian and Japanese subjects were 64.3%, 62.8% and 70.3%, respectively, and the corresponding values for the 80 mg dose were 94.8%, 90.6% and 90.6% respectively. The changes in serum gastrin were not clinically significant between all three ethnicities. The systemic exposure of DWP14012 was similar between the three ethnicities after the 40 mg doses but slightly lower in Caucasian and Japanese subjects after the 80 mg doses. Gastric acid suppression by DWP14012 showed a clear exposure-response relationship in the three ethnicities. CONCLUSIONS: Gastric acid suppression by DWP14012 was similar among the Korean, Caucasian and Japanese subjects in this study, and the PK, PK-PD relationships and safety were also similar among the three ethnicities. DWP14012 could be used without consideration of ethnicity.