NXT007 is a bispecific antibody that mimics the cofactor function of activated factor (F)VIII and was engineered by modifying emicizumab. Nonclinical investigations suggested its potential to provide nonhemophilic concentrations of coagulation activity to people with hemophilia A. A first-in-human, single-ascending dose study of NXT007 was conducted in healthy Japanese male adults (part A of the NXTAGE study). To evaluate safety, immunogenicity, pharmacokinetics, and pharmacodynamics of NXT007. Forty participants were enrolled across 5 cohorts and randomized to receive a single subcutaneous injection of NXT007 (n = 6 per cohort; 0.0018, 0.0054, 0.018, 0.054, or 0.18 mg/kg) or placebo (n = 2 per cohort). There were no dose-dependent increases in the incidence of adverse events, and no thrombotic events or injection-site reactions were reported. One serious adverse event of erythema was reported in a participant who received NXT007 0.0054 mg/kg, and its causality to NXT007 could not be ruled out. Nine participants developed anti-NXT007 antibodies; all were considered to be associated with faster clearance of NXT007 without impacting safety. NXT007 exposure increased dose-dependently but less than dose proportionally. The elimination half-life of NXT007 was approximately 10 weeks in antidrug antibody-negative participants. With ex vivo neutralization of endogenous FVIII in plasma samples, activated partial thromboplastin time was shortened, and thrombin generation was promoted in a dose-dependent manner. A single subcutaneous injection of NXT007 was well tolerated without occurrence of thrombotic events. The long half-life, pharmacological effect, and safety profile supported study progression to the subsequent multiple ascending dose parts of the NXTAGE study in people with hemophilia A.

Children with Kawasaki disease are prescribed acetylsalicylic acid powder as an antipyretic analgesic and antiplatelet agent; however, some of it remains in the mouth, leading to a bitter or sour taste. To address this issue, an in-hospital mini-tablet formulation of acetylsalicylic acid was developed. In order to use the mini-tablets safely and effectively, dissolution tests alone are not sufficient. Therefore, an open-label crossover study on six healthy participants was conducted to evaluate comparative pharmacokinetic parameters. The pharmacokinetic parameters of salicylic acid were C_max: 4.80 ± 0.79 mg/L (powder; P), 5.03 ± 0.97 mg/L (mini-tablet; MT), AUC_0–12: 18.0 ± 3.03 mg-h/L (P), 18.9 ± 4.59 mg-h/L (MT), those of acetylsalicylic acid C_max: 0.50 ± 0.20 mg/L (P), 0.41 ± 0.24 mg/L (MT), AUC_0–12: 0.71 ± 0.27 mg-h/L (P), 0.61 ± 0.36 mg-h/L (MT), with no significant differences between the mini-tablet and powder formulations. Although pharmacokinetic results obtained from adults cannot be directly applied to children, the results of this study are important for predicting pharmacokinetics. Furthermore, a formulation that can improve medication adherence in children who have difficulty taking acetylsalicylic acid powder, thus contributing to pediatric drug therapy.

Background/Objective: It is not uncommon for elderly patients to experience difficulties with feeding and swallowing. In the simple suspension method, tablets are dissolved and suspended in warm water without prior crushing or decapsulation, and then administered via a tube. Despite the prevalence of this method, the pharmacokinetics of suspended tablet dosage forms remain poorly understood. Methods: Verapamil was employed in dissolution tests following both the simple suspension and crushing methods. A pharmacokinetics study was conducted on healthy adult males. Results: The resultant dissolution profiles from the two methods exhibited notable dissimilarities. Drug release from the crushed product commenced earlier than that from the simple suspension and intact tablet. Furthermore, the area under the curve for verapamil during the initial 24 h period was 1.7 and 1.3 times greater in the crushed and simple suspension groups, respectively, than in the tablet group. Conclusions: The crushing and simple suspension methods are safe techniques for administering medications to patients with dysphagia, thereby preventing aspiration. Nevertheless, the processing of medications may result in an increased frequency of adverse effects. It is recommended that the processing of medicines prior to administration be avoided.

Background: Patients under cardiopulmonary resuscitation (CPR) are at high risk of aspirating gastric contents. Nasogastric tube insertion (NGTI) after tracheal intubation is usually performed blindly. This sometimes causes laryngopharyngeal mucosal injury (LPMI), leading to severe bleeding. This study clarified the incidence of LPMI due to blind NGTI during CPR. Methods: We retrospectively analyzed 84 patients presenting with cardiopulmonary arrest on arrival, categorized them into a Smooth group (Smooth; blind NGTI was possible within 2 min), and Difficult group (blind NGTI was not possible), and consequently performed video laryngoscope-assisted NGTI. The laryngopharyngeal mucosal condition was recorded using video laryngoscope. Success rates and insertion time for the Smooth group were calculated. Insertion number and LPMI scores were compared between the groups. Each regression line of outcome measurements was obtained using simple regression analysis. We also analyzed the causes of the Difficult group, using recorded video laryngoscope-assisted videos. Results: The success rate was 78.6% (66/84). NGTI time was 48.8 ± 4.0 s in the Smooth group. Insertion number and injury scores in the Smooth group were significantly lower than those in the Difficult group. The severity of LPMI increased with NGT insertion time and insertion number. Conclusions: Whenever blind NGTI is difficult, switching to other methods is essential to prevent unnecessary persistence.

Background/Objectives: Mini-tablets are a novel pediatric dosage form designed to mask drug taste and facilitate easier administration. This study aimed to assess the feasibility and acceptability of uncoated acetylsalicylic acid (ASA) mini-tablets in Japanese children with Kawasaki disease (KD) aged 1 to 4 years. Methods: A retrospective case series study of three pediatric patients with KD treated with ASA mini-tablets (3 mm diameter, 10 mg) was conducted at Showa University Hospital. ASA mini-tablets were administered for up to 68 days. Caregivers recorded daily medication intake and any issues in medication logbooks. Results: All three patients successfully took 100% of the prescribed doses. No adverse events related to mini-tablet ingestion were reported. Patients could take the mini-tablets for extended periods (63–68 days) as part of their KD treatment. Conclusions: ASA mini-tablets showed potential acceptability in this small cohort of pediatric patients with KD. This study represents the first investigation into the acceptability of mini-tablets containing active ingredients in Japanese pediatric patients. Larger studies are needed to confirm these findings and evaluate long-term safety and efficacy.