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Gepotidacin is a novel, bactericidal, first‐in‐class triazaacenaphthylene antibiotic in late‐phase development for uncomplicated urinary tract infection and uncomplicated urogenital gonorrhea. Two clinical studies were conducted to assess the pharmacokinetics (PK) and interethnic comparisons of oral gepotidacin (free‐base and to‐be‐marketed mesylate formulations) administered as single doses ranging from 1500 to 3000 mg in fed and fasted states, and as 2 × 3000‐mg doses given 12 hours apart under fed conditions in healthy participants of Japanese ancestry. Dose proportionality was observed in plasma exposures, and comparable area under the concentration‐time curve (AUC) and maximum concentration were observed in fed and fasted states. Interethnic comparisons for Japanese versus non‐Japanese participant data showed slightly higher plasma maximum concentration (7%‐30%) yet similar plasma AUCs; slightly lower urine AUCs (11%‐18%) were observed. The slightly higher plasma exposures in healthy Japanese versus White participants in the same study were attributed to lower mean body weights (64 kg versus ≈80 kg). Adverse events were primarily gastrointestinal, and when administered with food, gastrointestinal tolerability was improved. Overall, the gepotidacin PK and safety‐risk profiles in healthy Japanese support potential evaluation of the global clinical doses in future studies. [ABSTRACT FROM AUTHOR]

GSK2330672 is an inhibitor of the ileal bile acid transporter, designed to have minimal systemic exposure, and is under development as a potential therapeutic for pruritus associated with primary biliary cholangitis and other cholestatic liver diseases. A phase 1, double‐blind, placebo‐controlled, 4‐period crossover study was conducted to evaluate the safety, tolerability, and pharmacokinetic/pharmacodynamic characteristics of GSK2330672 in healthy Japanese participants. Sixteen healthy male participants received single oral doses of GSK2330672 (10‐180 mg) or placebo in each period. No serious adverse events and no adverse events leading to study discontinuation or withdrawal were reported. Drug‐related adverse events reported included gastrointestinal symptoms (mostly diarrhea) and positive fecal occult blood tests, and were all mild and resolved without any interventions. GSK2330672 was undetectable in the majority of participants' plasma. Pharmacodynamic observations included a tendency for total serum bile acids to reduce and for serum 7α‐hydroxy‐4‐cholesten‐3‐one, a key intermediate of bile acid synthesis, to increase with increasing doses of GSK2330672. In the context of recently published indications of potential efficacy for cholestatic pruritus in non‐Japanese populations, these data support further evaluations of GSK2330672 in Japanese patients. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the safety, tolerability, and pharmacokinetics of single and repeat doses of nemiralisib administered via a dry powder inhaler to healthy Japanese subjects. This was a single‐center, double‐blind, randomized, placebo‐controlled, parallel, single‐ and repeat‐ascending‐dose study. Thirty‐six healthy Japanese male subjects were randomized to receive either 1 dose strength of nemiralisib or placebo. The study consisted of a screening period, a single‐dose session (session 1), a repeat‐dose session (session 2), a 10‐day washout period between the sessions, and then a follow‐up visit 10 ± 1 days after the last dose of session 2. No serious adverse events were reported. No clinically significant abnormalities were found in clinical laboratory results, vital signs, or spirometry results. Generally, exposure (maximum observed plasma concentration [Cmax] and area under the concentration‐time curve [AUC]) increased with dose in an approximately proportional manner. Plasma Tmax was achieved rapidly at approximately 0.08 hours, and the terminal elimination half‐life (T1/2) was approximately 40 hours. Tmax and T1/2 did not change between days or doses in the single‐ and repeat‐dose sessions. Following 10 daily doses of 200, 500, and 700 μg nemiralisib, accumulation was observed, and the ratios (session 2, day 10:session 1) for Ro(AUC0‐24) and R(Cmax) were 2.4‐3.0 and 1.5‐1.7, respectively. Steady state was achieved by 6‐7 days, based on trough observed plasma drug concentration (Ctrough) values. [ABSTRACT FROM AUTHOR]