Safety, Tolerability, and Pharmacokinetics of a Novel Anti-obesity Agent, S-309309, in Healthy Adults with or Without Obesity.

Background: Anti-obesity medications are recommended for patients who do not achieve and maintain weight loss despite lifestyle interventions. S-309309 is a novel oral inhibitor of monoacylglycerol O-acyltransferase 2 being developed as a treatment for obesity.

Objective: The objective of the study was to investigate the safety, clinical pharmacology, pharmacokinetics and pharmacodynamic biomarker of S-309309.

Generation of multi-photon Fock states at telecommunication wavelength using picosecond pulsed light.

Multi-photon Fock states have diverse applications such as optical quantum information processing. For the implementation of quantum information processing, Fock states should be generated within the telecommunication wavelength band, particularly in the C-band (1530-1565 nm). This is because mature optical communication technologies can be leveraged for transmission, manipulation, and detection.

Treatment with ensitrelvir for COVID-19 in hospitalized patients of very advanced age: Case series.

Introduction: Ensitrelvir fumaric acid (ensitrelvir) is an orally active 3C-like protease inhibitor used to treat severe acute respiratory syndrome coronavirus 2 infection. Ensitrelvir was granted an emergency use authorization in Japan in 2022, but reports on the effectiveness and safety of ensitrelvir in actual clinical settings are limited.

Methods: Here, we report a case series of 9 patients with laboratory-confirmed symptomatic coronavirus disease of 2019 (COVID-19) who completed a 5-day course of ensitrelvir at Tomita Hospital from November 2022 to April 2023.

Prevention of post COVID-19 condition by early treatment with ensitrelvir in the phase 3 SCORPIO-SR trial.

This exploratory analysis of the double-blind, phase 3, SCORPIO-SR trial assessed the effect of ensitrelvir in preventing post coronavirus disease 2019 (COVID-19) condition (PCC). Patients with mild-to-moderate COVID-19 were randomized (1:1:1) within 120 h of symptom onset; received 5-day oral ensitrelvir 125 mg (375 mg on day 1), 250 mg (750 mg on day 1), or a matching placebo once daily; and were assessed for the severity of typical PCC symptoms using a self-administered questionnaire. In total, 341, 317, and 333 patients were assessed in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively (mean age, 35.

A SARS-CoV-2 recombinant spike protein vaccine (S-268019-b) for COVID-19 prevention during the Omicron-dominant period: A phase 3, randomised, placebo-controlled clinical trial.

Clinical trials of new vaccines based on existing variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are often impacted by the emergence of new virus variants. We evaluated the efficacy, immunogenicity, and safety of S-268019-b, a recombinant spike protein subunit vaccine based on the ancestral strain, for preventing symptomatic coronavirus disease 2019 (COVID-19) during the Omicron (BA.2)-dominant period in Vietnam.

A phase 3 randomized controlled trial of a COVID-19 recombinant vaccine S-268019-b versus ChAdOx1 nCoV-19 in Japanese adults.

We assessed S-268019-b, a recombinant spike protein vaccine with a squalene-based adjuvant, for superiority in its immunogenicity over ChAdOx1 nCoV-19 vaccine among adults in Japan. In this multicenter, randomized, observer-blinded, phase 3 study, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naïve participants (aged ≥ 18 years, without prior infection or vaccination against SARS-CoV-2) were randomized (1:1) to receive either S-268019-b or ChAdOx1 nCoV-19 as two intramuscular injections given 28 days apart. Participants who provided consent for a booster administration received S-268019-b at Day 211.

Ensitrelvir in patients with SARS-CoV-2: A retrospective chart review.

Antivirals with proven effectiveness against the Omicron SARS-CoV-2 variant are required for COVID-19 treatment in hospitalized patients, particularly those with severe underlying conditions. Ensitrelvir, a 3C-like protease inhibitor, received emergency approval in Japan in November 2022, based on evidence of rapid symptom resolution in non-hospitalized patients, but confirmation of its effectiveness in hospitalized patients is lacking. This retrospective chart review reports outcomes for all patients who received ensitrelvir whilst hospitalized with SARS-CoV-2 infection at Rinku General Medical Center, Japan (November 2022-April 2023).

Efficacy and Safety of 5-Day Oral Ensitrelvir for Patients With Mild to Moderate COVID-19: The SCORPIO-SR Randomized Clinical Trial.

Importance: Treatment options for COVID-19 are warranted irrespective of the presence of risk factors for severe disease.

Objective: To assess the efficacy and safety of ensitrelvir in patients with mild to moderate COVID-19.

Design, Setting, And Participants: This phase 3 part of a phase 2/3, double-blind, placebo-controlled randomized clinical trial was conducted from February 10 to July 10, 2022, with a 28-day follow-up period, at 92 institutions in Japan, Vietnam, and South Korea.

[Tetrodotoxin Content of the Small Gastropod Nassarius sufflatus].

Severe tetrodotoxin (TTX) poisoning due to small gastropods has been documented in Japan. In this study, we investigated the TTX content of the muscles and viscera of Nassarius sufflatus collected off the coast of Futaoi Island, Shimonoseki, Yamaguchi Prefecture, Japan, to prevent the occurrence of TTX poisoning caused by this small gastropod. Live specimens were obtained, and their muscles and viscera were collected.

Monitoring for adverse drug events of high-risk medications with a computerized clinical decision support system: a prospective cohort study.

Monitoring is recommended to prevent severe adverse drug events, but such examinations are often missed. To increase the number of monitoring that should be ordered for high-risk medications, we introduced a clinical decision support system (CDSS) that alerts and orders the monitoring for high-risk medications in an outpatient setting. We conducted a 2-year prospective cohort study at a tertiary care teaching hospital before (phase 1) and after (phase 2) the activation of a CDSS.

Safety and immunogenicity of a booster dose of S-268019-b: Interim findings of a Phase 3, open-label clinical study in Japan.

Despite the initial success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in prevention of symptomatic and severe diseases, booster vaccination has become increasingly important with the advent of variants with immune-escaping capacity. Herein, we report the safety and immunogenicity of S-268019-b, comprising SARS-CoV-2 spike protein and a squalene-based adjuvant, as a booster dose. We performed an interim analysis of an open-label, Phase 3 study data until Day 29 following S-268019-b booster in Japanese adults (aged 20-64 years) who had completed primary vaccination with mRNA-1273 and in Japanese elderly (aged ≥ 65 years) who had completed primary vaccination with mRNA-1273 or BNT162b2.

A Phase 1 Study of Ensitrelvir Fumaric Acid Tablets Evaluating the Safety, Pharmacokinetics and Food Effect in Healthy Adult Populations.

Background: A reported clinical pharmacokinetics and safety study of suspension formulation of ensitrelvir, a therapeutic agent used in severe acute respiratory syndrome coronavirus 2 infection, demonstrated favorable pharmacokinetics and was well tolerated in healthy male Japanese and White participants. Understanding the safety and pharmacokinetic features of ensitrelvir (using the formulation approved for clinical use) in various populations, and the effect of food, is crucial for optimal clinical use.

Objectives: The objectives of this study were to (1) assess the safety, tolerability, and pharmacokinetics of ensitrelvir following multiple-dose administration of ensitrelvir tablets in populations with different races, ages, and sex; and (2) assess the effect of food on the pharmacokinetics of ensitrelvir tablets in the fasted or fed state.

Evaluation of the Drug-Drug Interaction Potential of Ensitrelvir Fumaric Acid with Cytochrome P450 3A Substrates in Healthy Japanese Adults.

Background: Management of drug-drug interactions (DDIs) for ensitrelvir, a novel 3-chymotrypsin-like protease inhibitor of SARS-CoV-2 infection is crucial. A previous clinical DDI study of ensitrelvir with midazolam, a clinical index cytochrome P450 (CYP) 3A substrate, demonstrated that ensitrelvir given for 5 days orally with a loading/maintenance dose of 750/250 mg acted as a strong CYP3A inhibitor.

Objectives: The objectives of this study were to investigate the effect of ensitrelvir on the pharmacokinetics of CYP3A substrates, dexamethasone, prednisolone and midazolam, and to assess the pharmacokinetics, safety, and tolerability of ensitrelvir following multiple-dose administration of ensitrelvir.

Identification of a novel nonsense NOG mutation in a patient with stapes ankylosis and symphalangism spectrum disorder.

Multiple bone disorders due to mutations in the human noggin (NOG) causes a variety of phenotypes. Hearing impairment due to stapes ankylosis secondary to bony degeneration is also a feature of these syndromes. We describe the case of an individual in a Japanese family with conductive hearing loss due to stapes ankylosis and hyperopia and dactylosymphysis.

Evaluation of Drug-Drug Interactions of Ensitrelvir, a SARS-CoV-2 3CL Protease Inhibitor, With Transporter Substrates Based on In Vitro and Clinical Studies.

Drug-drug interaction potentials of ensitrelvir, a novel oral inhibitor of 3C-like protease of severe acute respiratory syndrome coronavirus 2, for drug transporters were evaluated by in vitro and clinical studies. The target drug transporters assessed were P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2, and multidrug and toxin extrusion 1 and 2K. In vitro study revealed that ensitrelvir is a substrate for P-gp and BCRP and inhibits P-gp, BCRP, OATP1B1, OATP1B3, OCT1, and OAT3.

Bidirectional sex change and plasticity of gonadal phases in the goby Lubricogobius exiguus.

Of the ca. 500 known hermaphroditic fish species, bidirectional sex change and simultaneous hermaphroditism are currently known in 69 and 57 species, respectively. Both bidirectional sex change and simultaneous hermaphroditism are predicted to evolve when mating opportunities are limited, such as in cases of low-density distribution and low mobility of individuals.

Effect of heterojunction structures on photoelectrochemical properties of ZnTe-based photocathodes for water reduction.

Photoelectrochemical (PEC) properties of ZnTe-based photocathodes with various structures were investigated to clarify the effective structure for the water reduction reaction. Samples with n-ZnO/ZnTe/p-ZnTe and n-ZnS/ZnTe/p-ZnTe heterostructures showed superior PCE properties to the samples without a heterojunction. In particular, the n-ZnS/ZnTe/p-ZnTe sample exhibited a large photocurrent even at a low applied potential in an electrolyte containing Eu ion as an electron scavenger.

Effectiveness of Expanded Instantaneous Input Dynamic Range Adjustment on Speech Perception.

Instantaneous input dynamic range (IIDR), as defined by Cochlear Ltd. (Sydney, Australia), refers to the acoustic level of short-term input dynamic range (IDR). Our aim was to evaluate the efficacy of expanding IIDR to improve speech understanding.

Results from a preclinical study in rodents and a Phase 1/2, randomized, double-blind, placebo-controlled, parallel-group study of COVID-19 vaccine S-268019-a in Japanese adults.

Background: In early 2020, developing vaccines was an urgent need for preventing COVID-19 from a contingency perspective.

Methods: S-268019-a is a recombinant protein-based vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprising a modified recombinant spike protein antigen adjuvanted with agatolimod sodium, a Toll-like receptor-9 agonist. In the preclinical phase, it was administered intramuscularly twice at a 2-week interval in 7-week-old mice.