Safety, Tolerability, Pharmacokinetics and Initial Pharmacodynamics of a Subcommissural Organ-Spondin-Derived Peptide:A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose First-in-Human Study

Introduction This randomized, double-blind, placebo-controlled study in healthy volunteers assessed the safety, tolerability, and pharmacokinetics of single ascending doses of intravenously administered NX210-a linear peptide derived from subcommissural organ-spondin-and explored the effects on blood/urine biomarkers and cerebral activity. Methods Participants in five cohorts (n = 8 each) were randomized to receive a single intravenous dose of NX210 (n = 6 each) (0.4, 1.25, 2.5, 5, and 10 mg/kg) or placebo (n = 2 each); in total, 10 and 29 participants received placebo and NX210, respectively. Blood samples were collected for pharmacokinetics within 180 min post dosing. Plasma and urine were collected from participants (cohorts: 2.5, 5, and 10 mg/kg) for biomarker analysis and electroencephalography (EEG) recordings within 48 h post dosing. Safety/tolerability and pharmacokinetic data were assessed before ascending to the next dose. Results The study included 39 participants. All dosages were safe and well tolerated. All treatment-emergent adverse events (n = 17) were of mild severity and resolved spontaneously (except one with unknown outcome). Twelve treatment-emergent adverse events (70.6%) were deemed drug related; seven of those (58.3%) concerned nervous system disorders (dizziness, headache, and somnolence). The pharmacokinetic analysis indicated a short half-life in plasma (6-20 min), high apparent volume of distribution (1870-4120 L), and rapid clearance (7440-16,400 L/h). In plasma, tryptophan and homocysteine showed dose-related increase and decrease, respectively. No drug dose effect was found for the glutamate or glutamine plasma biomarkers. Nevertheless, decreased blood glutamate and increased glutamine were observed in participants treated with NX210 versus placebo. EEG showed a statistically significant decrease in beta and gamma bands and a dose-dependent increasing trend in alpha bands. Pharmacodynamics effects were sustained for several hours (plasma) or 48 h (urine and EEG). Conclusion NX210 is safe and well tolerated and may exert beneficial effects on the central nervous system, particularly in terms of cognitive processing

Different phenotypes and factors associated with atopic dermatitis in the young adult Singaporean Chinese population: A cross-sectional study

Background: Atopic dermatitis (AD) is a chronic allergic disease typically accompanied by atopy and thus, a tendency to develop allergic diseases such as allergic rhinitis, asthma or food allergies. Currently, individuals with AD are classified into those presenting with AD alone and those presenting with AD along with other allergic diseases (AD+). It is important to identify the various endophenotypes of AD using anthropometric, environmental, socio-economic, and disease history data in order to improve disease management. To characterize the phenotypic differences among Singaporean Chinese individuals with AD alone and AD+, and identify the socioeconomic, lifestyle, and environmental factors associated with these different presentations. Methods: Based on data collected via a standardized/validated questionnaire, 4604 participants (mean age: 22.1 years) were classified into three groups: 1) AD alone group; 2) AD with other allergic diseases group (AD+); and 3) Control group. Results: Participants were less sensitized to common inhalant allergens in the AD alone group versus the Control group (67% vs. 72%, respectively; p  23) was associated with the disease and the difference was more pronounced in the AD alone group compared to the AD+ group (Odds Ratio: 1.38; 95% Confidence Interval: 1.4–1.67; p < 0.001). No major differences in habits were observed between the AD alone and AD+ groups. Conclusions: The two presentations of AD may have different underlying pathogenesis and associated risk factors. Keywords: Atopic dermatitis, Allergy, Singaporean Chinese population, Phenotypes, Risk factor