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Daprodustat is a prolyl hydroxylase inhibitor that stimulates erythropoiesis in a manner similar to the natural response to hypoxia, whereby inhibition of hypoxia inducible factor (HIF) prolyl‐4‐hydroxylases by daprodustat ultimately results in increased levels of HIF‐responsive genes. Daprodustat is under development as an emerging new class of agents for the treatment of anemia associated with chronic kidney disease (CKD). This was a single‐center, single‐dose, open‐label, randomized, 2‐way crossover study in healthy Japanese male participants consisting of 2 parts. The primary objective was to evaluate the bioequivalence (BE) between daprodustat tablet strengths (part 1) and to evaluate the food effect on the pharmacokinetics (PK) of daprodustat (part 2). A total of 64 healthy Japanese male participants were enrolled; 52 participants were included in part 1 and 12 in part 2. BE was demonstrated between the daprodustat 2‐mg tablet and the daprodustat 4‐mg tablet. A standard CKD meal did not have a large effect on the PK parameters of daprodustat after a single oral dose of daprodustat 4 mg. Administration of single oral doses of daprodustat 4 mg was generally well tolerated in the healthy Japanese participants, and no new safety signals were identified without regard to food. [ABSTRACT FROM AUTHOR]

Levocetirizine is classified as a second‐generation antihistamine. Levocetirizine is available for the treatment of allergic disorders such as allergic rhinitis and chronic idiopathic urticaria. This was a single‐center, single‐dose, open‐label, randomized, 2‐way crossover study in healthy Japanese male subjects consisting of 2 parts. Part 1 compared the bioavailability of levocetirizine oral disintegrating tablet (ODT) and levocetirizine immediate‐release tablet (IRT) taken with water in the fasted state in 24 subjects; all subjects completed this part of the trial. In part 2, the bioavailability of levocetirizine ODT without water was compared with that of levocetirizine IRT with water in the fasted state in 48 subjects; 47 subjects completed this part of the trial. Bioequivalence was demonstrated between levocetirizine IRT 5 mg and ODT 5 mg. The safety profiles were generally similar between levocetirizine ODT and levocetirizine IRT, with no serious adverse events, deaths, or adverse events leading to withdrawal reported during the study. [ABSTRACT FROM AUTHOR]

Danirixin is a selective and reversible CXC chemokine receptor 2 antagonist that may be useful for the treatment of respiratory diseases such as chronic obstructive pulmonary disease. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of danirixin after administration of single oral doses of 10, 50, and 100 mg danirixin hydrobromide (HBr) tablets in the fed state (high‐fat meal) (part 1) and to evaluate the food effect (low‐fat meal) on the pharmacokinetics of danirixin after administration of a single oral dose of 50 mg danirixin HBr tablets (part 2). A total of 34 Japanese healthy elderly male participants were enrolled; 18 participants were included in part 1, and 16 in part 2. The systemic exposure to danirixin (maximum blood concentration [Cmax] and area under the concentration‐time curve [AUC0‐t]) increased in an approximately dose‐proportional manner. The exposure to danirixin was lower in the fed state (low‐fat meal) than in the fasted state (a 56% and 35% decrease in Cmax and AUC0‐t, respectively). This first study of danirixin in Japanese healthy elderly participants showed a favorable safety profile with no drug‐related adverse events and no clinically significant concerns in clinical laboratory values, vital signs, ocular examination, or electrocardiograms. [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]

Clindamycin 1%/benzoyl peroxide 3% fixed-dose combination gel (CLDM/BPO3%) is a topical product for the treatment of acne vulgaris. In this study, plasma and urine concentrations of benzoic acid (BA) and hippuric acid (HA) were analyzed to estimate the pharmacokinetics (PK) of BPO after application of CLDM/BPO3% twice-daily for 7 days in Japanese patients with acne vulgaris. Seven-day repeated application of CLDM/BPO3% appears to be safe in this patient population. Concentrations of plasma and urine BA were below the limit of quantification before and after repeated application in most of the 12 adult male patients. Mean difference in Cmax and AUC0-last for plasma HA indicated increased exposures after repeated application, but with wide 90% confidence intervals. Mean Ae0-12 for urine HA was similar before and after repeated application. Repeated application of CLDM/BPO3% is thus unlikely to result in accumulation of BA and HA. The study suggests negligible systemic exposure to BPO metabolites from CLDM/BPO3% after 7-day repeated application in male patients with acne vulgaris. [ABSTRACT FROM AUTHOR]