Safety, tolerability, and pharmacokinetics of HRS9432(A) injection in healthy Chinese subjects: a phase-I randomized, double-blind, dose escalation, placebo-controlled study.

HRS9432(A) is a long-acting echinocandin antifungal medication primarily used to treat invasive fungal infections, particularly invasive candidiasis. The safety, tolerability, and pharmacokinetic characteristics of HRS9432(A) injection were investigated in a randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose Phase I study involving 56 healthy adult subjects. Doses ranging from 200 to 1200 mg were administered. Safety was continually monitored, including adverse events, clinical laboratory examinations, vital signs, 12-lead electrocardiograms, and physical examinations, while the pharmacokinetic profile within the body was evaluated. The results indicated that concentrations of HRS9432 peaked immediately after infusion, demonstrating essentially linear pharmacokinetic characteristics within the dosage range of 200-1,200 mg. It exhibited a low clearance rate and an extended half-life, with a clearance of approximately 0.2 L/h, a volume of distribution of around 40 L, and a half-life of approximately 140h following a single dose. The accumulation index for AUC0-τ after multiple doses ranged from 1.41 to 1.75. No severe adverse events occurred during the study, and the severity of all adverse events was mild or moderate. Therefore, the intravenous administration of HRS9432(A) in healthy Chinese adult subjects, either as multiple infusions of 200 to 600 mg (once a week, four doses) or as a single infusion of 900-1,200 mg, demonstrated overall good safety and tolerability. The pharmacokinetic exhibited essentially linear characteristics in the body, supporting a weekly dosing frequency for clinical applications and providing additional options for the treatment or prevention of invasive fungal infections. CLINICAL TRIALS: This study is registered with the International Clinical Trials Registry Platform as ChiCTR2300073525.

Use of micafungin as antifungal prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Spain (GETH-MIC) / Profilaxis antifúngica con micafungina en pacientes que reciben un trasplante alogénico de progenitores hematopoyéticos (alo-TPH) en España (GETH-MIC)

INTRODUCTION: The fungal infections remain an important problem in the allogeneic stem cell trasnsplantation (allo-SCT) setting and thus, anti-fungal prophylaxis is commonly used. The antifungal drug should offer activity, at least against Candida and Aspergillus spp., a good safety profile and low probability interactions. Micafungin could theoretically fulfill these requisites. The aim of the study was to describe the experience with micafungin as primary prophylaxis in patients undergoing allo-SCT in a cohort of Spanish centres, and to evaluate its efficacy and tolerability in this population. MATERIAL AND METHODS: Retrospective multicentre observational study including all consecutive adult patients admitted for allo-SCT in participating centres of the Grupo Español de Trasplante Hematopoyético (GETH), from January 2010 to December 2013, who received micafungin as primary prophylaxis during the neutropenic period. RESULTS: A total of 240 patients from 13 centres were identified and 159 patients were included for the analysis. Most patients (95.6%) received 50 mg/day of micafungin. During the follow-up, 7 (4.4%) patients developed breakthrough invasive fungal disease, 1 proven and 6 probable; one patient discontinued the drug because of serious drug interactions. Prophylaxis with micafungin was considered effective in 151 (94.9%) patiens. CONCLUSIONS: According to our experience, micafungin is an appropriate alternative for antifungal prophylaxis in patients undergoing an allo-HSCT, because its efficacy, its low profile of drug interactions and side-effects

INTRODUCCIÓN: Las infecciones fúngicas siguen representando un problema en el trasplante alogénico de progenitores hematopoyéticos (alo-TPH) por lo que es habitual el uso de profilaxis antifúngica en estos PACIENTES: El tratamiento antifúngico debe presentar al menos actividad frente a Candida y Aspergillus spp, un buen perfil de seguridad y baja probabilidad de infecciones, siendo micafungina una de las opciones que podría cumplir todos estos requisitos. El objetivo del estudio fue describir la experiencia con micafungina como profilaxis primaria en pacientes sometidos a alo-TPH en una cohorte de hospitales españoles, y evaluar su eficacia y seguridad en esta población. MATERIAL Y MÉTODOS: Estudio retrospectivo multicéntrico observacional consecutivo de todos los pacientes adultos ingresados para alo-TPH en los centros del Grupo Español de Trasplante Hematopoyético (GETH) desde enero de 2010 a diciembre de 2013 y que recibieron micafungina como profilaxis primaria durante el periodo de neutropenia. RESULTADOS: Se identificaron 240 pacientes de 13 hospitales y 159 fueron incluidos para el análisis. La mayoría (95.6%) de ellos recibieron dosis de 50mg/día de micafungina. Durante el seguimiento, 7 (4.4%) pacientes desarrollaron infecciones de brecha, 1 probada y 6 probables; en un paciente se suspendió el tratamiento por interacciones medicamentosas graves. La profilaxis con micafungina se consideró efectiva en el 94,9% de los pacientes (151 de 159). CONCLUSIONES: En base a nuestros resultados, consideramos que micafungina es una buena alternativa como profilaxis antifúngica en pacientes sometidos a alo-TPH, por su eficacia, el bajo riesgo de interacciones y de efectos adversos