Acadia Pharmaceuticals (United States)

Trofinetide is an approved treatment in the USA and Canada for Rett syndrome in patients aged ≥ 2years. Trofinetide is currently supplied as a ready-to-use oral solution (TOS). A new trofinetide powder for oral solution (TPOS) offers potential advantages: smaller configuration of unit-dose packs; excludes preservatives, synthetic red dye, and maltitol; can be dissolved in a range of volumes in cold/room temperature water or water-based beverages; does not require refrigeration. To ensure that the formulation change does not impact trofinetide pharmacokinetics, a bioequivalence study assessed trofinetide pharmacokinetics after single 12,000-mg oral trofinetide doses administered as TOS and TPOS and the impact of a reduced constitution volume on trofinetide bioavailability. In this randomized, open-label, three-period, three-treatment design study, 38healthy adults each received one 12,000-mg trofinetide dose of TOS (60mL [200mg/mL]; treatmentA), TPOS constituted in 60mL of water (200mg/mL; treatmentB), and TPOS constituted in 25mL of water (480mg/mL; treatmentC) in sequence ABC or BAC. Bioequivalence for each treatment comparison was confirmed if the 90% confidence interval (CI) of the geometric mean ratio (GMR) for the maximum observed drug concentration (Cmax), area under the concentration-time curve from time0 to time t (AUC0-t), and AUC from time0 to infinity (AUC0-∞) fell within 80-125%. The criteria for bioequivalence were met for AUC0-t (GMR 99.62%; CI 96.52-102.83), AUC0-∞ (GMR 99.50%; CI 96.44-102.66), and Cmax (GMR 99.52%; CI 94.99-104.27) between treatmentB and treatmentA. All other treatment comparisons (C vs A and B vs C) also met the bioequivalence criteria. The most frequent treatment-emergent adverse event was diarrhea (n = 6 [15.8%]). No serious or unexpected adverse events occurred during the study. The bioequivalence demonstrated in this study supports the clinical interchangeability of TPOS and TOS and shows that TPOS can be constituted using adjustable volumes of water without affecting bioavailability. There were no unexpected adverse events reported with trofinetide when administered as TPOS and TOS.

BackgroundPimavanserin is approved by the US Food and Drug Administration for the treatment of hallucinations and delusions associated with Parkinson’s disease. We analyzed the effect of pimavanserin on psychosis in patients with Lewy body dementia, including Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB), from the phase 3 HARMONY trial.MethodsThis subgroup analysis included patients with PDD or DLB from HARMONY, a previously completed, multicenter, randomized, discontinuation study of pimavanserin for dementia-related psychosis. Patients with moderate to severe psychosis received pimavanserin 34 mg once daily for 12 weeks (open-label treatment). Those who achieved a sustained response at weeks 8 and 12 were randomized to continue treatment with pimavanserin or discontinue treatment and receive placebo for up to 26 weeks in the double-blind period. The primary endpoint was the time to psychosis relapse as defined by prespecified criteria. Safety was evaluated by adverse events; effects on motor symptoms and cognitive abilities were also assessed.ResultsOverall, 392 patients were enrolled in HARMONY; 49 patients with PDD and 27 patients with DLB were included in the open-label safety analysis, of whom 46 met response criteria and were randomized to receive pimavanserin (n = 22) or placebo (n = 24) during the double-blind period. Psychosis relapse risk was significantly lower with pimavanserin vs. placebo (hazard ratio, 0.031; 95% CI, 0.010–0.103; 2-sided nominal P < 0.0001). Fewer than 50% of patients experienced an adverse event in either treatment period; pimavanserin did not negatively affect motor or cognitive function.ConclusionsPsychosis relapse risk was significantly lower with pimavanserin vs. placebo in patients with Lewy body dementia. Pimavanserin was also well tolerated and did not worsen motor or cognitive function. Results should be interpreted cautiously since this study is a post hoc analysis of a previous trial that was not originally designed or powered to draw clinical conclusions based on dementia subgroups.Trial registrationClinicalTrials.gov Identifier: NCT03325556 (registered 18 October 2017).

As verminoses permanecem como um desafio relevante para a saúde pública no Brasil, especialmente em áreas com baixa renda e serviços básicos precários. Essas doenças parasitárias afetam principalmente crianças em idade escolar, prejudicando seu desenvolvimento físico, cognitivo e social. Para combatê-las de forma eficaz, é fundamental adotar uma abordagem integrada, que vá além do tratamento medicamentoso e trate as condições que favorecem a transmissão dos parasitas. Isso inclui a união de esforços entre os setores de saúde, educação, saneamento e assistência social. A realização regular de campanhas de desparasitação, a melhoria do acesso ao saneamento e a promoção de ações educativas têm se mostrado eficazes quando implementadas de maneira coordenada. Este estudo visa analisar essas estratégias, destacando exemplos bem-sucedidos e os desafios na sua execução.

held in-person at the Department of Earth Sciences, Memorial University, on February 27 and 28.However, oral presentations were also available to be viewed virtually.This year the meeting kicked off on Thursday morning with introductory remarks from the GAC-NL President, Roderick Smith.The rest of the conference was taken up by presentations on a wide range of geoscience topics.

Arctic biodiversity is under threat from both climate-induced environmental change and anthropogenic activity. However, the rapid rate of change and the challenging conditions for studying Arctic environments mean that many research questions must be answered before we can strategically allocate resources for management. Addressing threats to biodiversity in the Arctic is further complicated by the region's complex geopolitics, as eight countries claim jurisdiction over the area, with multiple local considerations such as Indigenous sovereignty and resource rights. Here, we identify research priorities to serve as a starting point for addressing the most pressing threats to Arctic biodiversity. We began by collecting pressing research questions about Arctic biodiversity, thematizing them as either threats or actions, and then categorizing them further into 18 groups. Then, drawing on cross-disciplinary and global expertise of professionals in Arctic science, management, and policy, we considered the barriers to answering these questions and proposed potential solutions that could be implemented if barriers were overcome. Overall, our horizon scan provides an expert assessment of threats (e.g., species’ responses to climate change) and actions (e.g., a lack of fundamental information regarding Arctic biodiversity) needing attention and is intended to guide future conservation action within the Arctic.