Concentration-QTc analysis of soticlestat in healthy adults: An alternative to a thorough QT study.

Aim: This study aimed to examine the cardiac and overall safety and pharmacokinetic (PK) profiles of soticlestat (TAK-935), an oral, first-in-class selective cholesterol 24-hydroxylase inhibitor.

Methods: Data came from a randomised, phase 1 study of soticlestat in 33 healthy Japanese adults (NCT04461483); 24 adults in Part 1 (single-dose soticlestat 200-1200 mg or placebo) and 9 in Part 2 (soticlestat 100-300 mg twice daily or placebo for 21 days). PK sample collection was paired with 12-lead electrocardiogram data from continuous Holter recordings.

Narrow-band imaging with magnification for the diagnosis of colorectal adenoma in a patient with Cronkhite-Canada syndrome.

Cronkhite-Canada syndrome (CCS) is a rare disease characterized by gastrointestinal polyposis, skin pigmentation, alopecia, and abnormal nailfolds. Although colorectal cancer has been reported in patients with CCS, reports are limited regarding the effectiveness of the usage of image-enhanced endoscopy in CCS lesions. Here, we report a case of CCS in which narrow-band imaging (NBI) magnifying endoscopy was applied to detect an adenomatous component in multiple hamartomatous polyps.

Cardiovascular risk factors are associated with augmented thrombogenicity in healthy individuals: analysis using the Total Thrombus-formation Analysis System.

Background: Rupture of an atherosclerotic plaque and subsequent exposure of the subendothelial prothrombotic matrix to blood cause arterial thrombosis. Circulating platelets play an indispensable role in the growth of arterial thrombi partially owing to their unique ability to adhere to the subendothelial matrix and to aggregate to each other under flow conditions. Recently, the Total Thrombus-formation Analysis System (T-TAS) was developed for ex vivo analysis of the thrombogenic potential of whole blood samples under flow conditions.

Food Effect on a Single High Dose of Carotegrast Methyl, an Oral Antagonist of α4-Integrin, in Healthy Male Subjects: A Randomised, Placebo-Controlled, Double-Blind Study.

Background And Objectives: Carotegrast methyl, a novel prodrug, oral antagonist of α4-integrin, is in development for the treatment of active ulcerative colitis. This randomised, placebo-controlled, double-blind, crossover study evaluated the effect of food on the pharmacokinetics and pharmacodynamics as well as the safety profile after a single dose of carotegrast methyl in healthy male subjects.

Methods: Subjects were randomised to receive a single dose of carotegrast methyl (240, 480 or 960 mg) or placebo in a 6:2 ratio and received the study drug under both fed and fasted conditions separated by an 8-day washout.

Pharmacokinetic study of lascufloxacin in non-elderly healthy men and elderly men.

We conducted this phase I clinical study to examine the pharmacokinetic profiles and safety of lascufloxacin (LSFX), a novel quinolone antibacterial agent, in non-elderly Japanese healthy men and the effects of aging on LSFX pharmacokinetics in elderly Japanese healthy men. 1. After single-dose oral administration of LSFX 100-800 mg (capsules) to six healthy adults in fasting state, the C and AUC roughly increased in proportion to the doses.

Effects of mild and moderate renal dysfunction on pharmacokinetics, pharmacodynamics, and safety of dotinurad: a novel selective urate reabsorption inhibitor.

Background: Dotinurad, a novel selective urate reabsorption inhibitor, exerts a serum uric acid-lowering effect by selectively inhibiting urate transporter 1 (URAT1) in patients with hyperuricemia. It is generally known that the progression of renal dysfunction is associated with a reduction in the serum uric acid-lowering effects of uricosuric drugs. We, therefore, investigated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of dotinurad in subjects with renal dysfunction.

AJM300, a novel oral antagonist of α4-integrin, sustains an increase in circulating lymphocytes: A randomised controlled trial in healthy male subjects.

Aims: AJM300 is an oral antagonist of α4-integrin that reduces inflammation by blocking leucocyte trafficking. This study aimed to investigate safety, tolerability, pharmacokinetics and pharmacodynamics of AJM300 in healthy male subjects.

Methods: A total of 23 subjects were randomised to receive 240 mg (n = 6), 480 mg (n = 5), 960 mg (n = 6) of AJM300 or the corresponding placebo (n = 2 per group).

Relative and Absolute Bioavailability Study of Emicizumab to Bridge Drug Products and Subcutaneous Injection Sites in Healthy Volunteers.

Emicizumab (ACE910) is a bispecific antibody that is a novel, subcutaneously injectable treatment for patients with hemophilia A. This study assessed the relative bioavailability of emicizumab between old and new drug products (DPs) and among 3 commonly used subcutaneous injection sites (abdomen, upper arm, and thigh), together with its absolute bioavailability in healthy volunteers. Forty-eight healthy volunteers were randomized into 4 groups to receive a single subcutaneous injection of 1 mg/kg with the old or new DP, and another 12 volunteers each received a single, 90-minute, intravenous infusion of 0.

Pharmacokinetics, Safety, and Tolerability of Cefiderocol, a Novel Siderophore Cephalosporin for Gram-Negative Bacteria, in Healthy Subjects.

Cefiderocol is a novel parenteral siderophore cephalosporin that shows potent efficacy against various Gram-negative bacteria, including carbapenem-resistant strains, and in preclinical models of infection. The aim of the present study was to evaluate the pharmacokinetics (PK), safety, and tolerability of cefiderocol after both single and multiple dosing by intravenous infusion over 60 min in healthy adult subjects. A single-ascending-dose study at doses of 100, 250, 500, 1,000, and 2,000 mg was conducted in 40 healthy Japanese males and females (6 individuals receiving the active drug and 2 individuals receiving a placebo per cohort).

Pharmacokinetics and Pharmacodynamics of Tofogliflozin (a Selective SGLT2 Inhibitor) in Healthy Male Subjects.

Tofogliflozin is a selective oral inhibitor of sodium-glucose co-transporter 2 for treatment of type 2 diabetes mellitus. The pharmacokinetics, pharmacodynamics, and safety of tofogliflozin were investigated in healthy male subjects. Three studies were conducted: single-ascending dose study (10-640 mg) in 56 Japanese and 24 Caucasian subjects; multiple-ascending dose study (2.

Evaluation of the Pharmacokinetics and Pharmacodynamics of Prasugrel in Japanese Elderly Subjects.

Background And Objective: An increased incidence in bleeding events has been reported in Western elderly patients receiving prasugrel. Therefore, doses in Japanese elderly subjects need to be carefully determined. We assessed the pharmacokinetic and pharmacodynamic effects of prasugrel at the clinical dose used in Japan in healthy Japanese elderly subjects compared with non-elderly subjects.

Pharmacokinetics and safety of intravenous peramivir, neuraminidase inhibitor of influenza virus, in healthy Japanese subjects.

Background: Intravenous peramivir is a potent neuraminidase (NA) inhibitor with activity against influenza A and B viruses. The early use of NA inhibitors has been shown to reduce mortality in influenza patients.

Methods: To evaluate the pharmacokinetics of peramivir and confirm the safety and tolerability of multiple infusions of peramivir in healthy Japanese subjects, two Phase I, single-centre, randomized, double-blind and placebo-controlled studies consisting of a multiple-dose study and a high-dose study were conducted.

Whole-body patterns of the range of joint motion in young adults: masculine type and feminine type.

Background: Understanding the whole-body patterns of joint flexibility and their related biological and physical factors contributes not only to clinical assessments but also to the fields of human factors and ergonomics. In this study, ranges of motion (ROMs) at limb and trunk joints of young adults were analysed to understand covariation patterns of different joint motions and to identify factors associated with the variation in ROM.

Methods: Seventy-eight healthy volunteers (42 males and 36 females) living on Okinawa Island, Japan, were recruited.

Geographic variation in nasal cavity form among three human groups from the Japanese Archipelago: Ecogeographic and functional implications.

Objectives: Geographic variation in human nasal form has often been interpreted as a climatic adaptation, owing to the nasal air-conditioning function. The aim of this study was to further address morphofunctional issues of the nasal cavity, using three human groups from subarctic, temperate, and subtropical regions of the Japanese Archipelago: prehistoric Okhotsk, early-modern Honshu and Okinawa groups.

Methods: Using three-dimensional coordinates of craniometric landmarks surrounding the nasal cavity, we compared linear measurements regarding nasal cavity form among the three groups and also conducted 3D geometric morphometrics.

A Pharmacokinetic/Pharmacodynamic Drug-Drug Interaction Study of Tofogliflozin (a New SGLT2 Inhibitor) and Selected Anti-Type 2 Diabetes Mellitus Drugs.

Objective: Tofogliflozin is an oral hypoglycemic agent with a novel mechanism of action that reduces blood glucose levels by promoting glucose excretion in urine, achieved by selectively inhibiting sodium-glucose co-transporter 2 (SGLT2). We evaluated the effects of several selected anti-type 2 diabetes mellitus (T2DM) drugs-glimepiride, metformin, sitagliptin, pioglitazone, miglitol, nateglinide, and voglibose-on the pharmacokinetics and pharmacodynamics of tofogliflozin, and the effects of tofogliflozin on the pharmacokinetics of these anti-T2DM drugs in healthy male volunteers.

Methods: A single dose of either tofogliflozin alone, one of the anti-T2DM drugs alone, or co-administration of tofogliflozin and the anti-T2DM drug was administered to 108 healthy men.

Size and placement of developing anterior teeth in immature Neanderthal mandibles from Dederiyeh Cave, Syria: implications for emergence of the modern human chin.

Evolutionary and functional significance of the human chin has long been explored from various perspectives including masticatory biomechanics, speech, and anterior tooth size. Recent ontogenetic studies have indicated that the spatial position of internally forming anterior teeth partially constrains adult mandibular symphyseal morphology. The present study therefore preliminarily examined the size and placement of developing anterior teeth in immature Neanderthal mandibles of Dederiyeh 1 and 2, compared with similarly-aged modern humans (N = 16) and chimpanzees (N = 7) whose incisors are comparatively small and large among extant hominids, respectively.

Spatial relationship between the mental foramen and mandibular developing teeth in modern humans, chimpanzees, and hamadryas baboons.

The mental foramen (MF) of adult human mandibles is characterized by its high position and posterosuperior opening orientation, compared with that of nonhuman primates. In this study, to examine when and how such interspecies variations in MF position/orientation are manifested in the context of dental development, positional relationships between the MF and nearby forming teeth (dc, dm1, C, P3) were assessed using CT-scanned growth-series mandibles of the following three species with various MF positions and anterior dental sizes: modern humans, chimpanzees, and hamadryas baboons. Results showed that modern humans have more antero-superiorly located MF and dc than the two nonhuman samples during growth, whereas the MF and dm1 of hamadryas baboons are the most inferiorly positioned.

Comparative analysis of facial morphology between Okinawa Islanders and mainland Japanese using three-dimensional images.

Objectives: Differences in facial height and breadth between Okinawa Islanders and mainland Japanese have been reported in previous craniometric and somatometric studies. This study using three-dimensional (3D) images aimed to identify more detailed characteristics of facial morphology in each population.

Methods: Using a hand-held 3D scanner, we obtained 60 facial surface images each from Okinawa Islanders and mainland Japanese.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of apixaban in healthy Japanese male subjects.

Objective: This was a randomized, placebo-controlled, double-blind, sequential, ascending-dose study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of apixaban in healthy Japanese male subjects.

Methods: The study was conducted using three sequential dose panels: apixaban 2.5 mg, 5 mg, and 10 mg given twice daily.

Comparison of levocetirizine pharmacokinetics after single doses of levocetirizine oral solution and cetirizine dry syrup in healthy Japanese male subjects.

Objective: Levocetirizine, the R-enantiomer of cetirizine, is classified as a second generation antihistamine used for the treatment of allergic disorders. This study aimed to compare exposure to levocetirizine when given as levocetirizine oral solution (OS) 5 mg to that when given as cetirizine dry syrup (DS) 10 mg, which contains equal proportions of levocetirizine and dextrocetirizine, in healthy Japanese male subjects.

Methods: The study was conducted in an open-label, single dose, randomized and two-way cross-over design.

Pharmacokinetics of a Single 150-mg Intravenous Infusion of Fosaprepitant: Effects of Concentration and Infusion Time in Healthy Japanese Men.

Purpose: Fosaprepitant dimeglumine (Proemend® for Injection; formerly ONO-7847) is a phosphorylated prodrug that is rapidly converted to aprepitant, an oral selective neurokinin-1 receptor antagonist approved for the prevention of chemotherapy-induced nausea and vomiting. This Phase 1 study evaluated the pharmacokinetics, safety, and tolerability of fosaprepitant after a single intravenous dose in healthy Japanese men.

Methods: All fosaprepitant- or placebo-treated subjects were assessed for the occurrence of adverse events.

Geographic variation in body form of prehistoric Jomon males in the Japanese archipelago: its ecogeographic implications.

Diversity of human body size and shape is often biogeographically interpreted in association with climatic conditions. According to Bergmann's and Allen's rules, populations in regions with a cold climate are expected to display an overall larger body and smaller/shorter extremities than those in warm/hot environments. In the present study, the skeletal limb size and proportions of prehistoric Jomon hunter-gatherers, who extensively inhabited subarctic to subtropical areas in the ancient Japanese archipelago, were examined to evaluate whether or not the inter-regional differences follow such ecogeographic patterns.

Assessment of the immunogenicity and safety of varying doses of an MF59®-adjuvanted cell culture-derived A/H1N1 pandemic influenza vaccine in Japanese paediatric, adult and elderly subjects.

Introduction: Effective vaccination strategies are required to combat future influenza pandemics. Here we report the results of three independent clinical trials performed in Japan to assess the immunogenicity, tolerability and safety of varying doses of a cell culture-derived MF59(®)-adjuvanted A/H1N1 pandemic vaccine in healthy Japanese paediatric, adult and elderly subjects.

Methods: One hundred and twenty-three children (6 months-18 years), and 200 adults (19-60 years) were randomly assigned in a 1:1 ratio to receive two doses of vaccine containing either 7.

Interspecies difference in placement of developing teeth and its relationship with cross-sectional geometry of the mandibular symphysis in four primate species including modern humans.

The form of the anthropoid mandibular symphysis has recently been addressed in association with spatial requirements for the forming anterior teeth. To evaluate potential relationships between the symphyseal shape and teeth further, the growth patterns of the symphyseal region and the positioning of the tooth crypts were examined using CT data, comparing four primate species (modern humans, chimpanzees, Japanese monkeys, and hamadryas baboons) with varied symphyseal curvature and tooth size. First, results showed that interspecies differences in overall mandibular shape including symphyseal inclination and bicanine width are consistently expressed throughout postnatal ontogeny, although local symphyseal configurations related to the superior transverse torus (STT) tended to change considerably during growth in chimpanzees.