为了评估奥伊奥胆酮在库欣病患者中的长期疗效和安全性，进行了多中心、48周的III期LINC 4临床试验，并设有可选的延长期，最初计划延续至96周。患者可以在延长期内继续参与，直到当地获得管理访问计划或其他替代治疗，或在其研究中批准的方案修订规定的要求之一实现，要求患者在96周前的4周内进行治疗终点访视。延长期中评估的研究结果包括：平均尿游离皮质酮（mUFC）反应率；mUFC、血清皮质酮和深夜唾液皮质酮（LNSC）的变化；心血管和代谢相关参数的变化；血压、腰围和体重的变化；库欣病体征的改变；与健康相关生活质量的患者报告结果的变化；肿瘤体积的变化；以及不良事件的情况。结果进行了描述性分析，未进行正式的统计检验。 共有60名进入试验的患者，53名完成了延长期，其中29名患者接受了超过96周的奥伊奥胆酮治疗（奥伊奥胆酮的中位持续时间：87.1周）。在核心试验期间观察到的mUFC正常化患者比例在延长期期间得以维持。在试验结束时，72.4%的患者达到了mUFC正常范围。同时还观察到了血清皮质酮和LNSC的显著降低。在核心试验期间观察到的大多数心血管和代谢相关参数的改善，以及库欣病的体征改善，在延长期内得以维持或继续改善。奥伊奥胆酮耐受性良好，其安全性与先前报告一致。 奥伊奥胆酮提供了长期的皮质酮分泌控制，并伴随临床体征和过度皮质酮症的持续改善。奥伊奥胆酮是库欣病患者的有效长期治疗方法。 ClinicalTrials.gov，编号NCT02180217。 版权所有 © 2023 Gadelha、Snyder、Witek、Bex、Belaya、Turcu、Feelders、Heaney、Paul、Pedroncelli和Auchus。

To evaluate the long-term efficacy and safety of osilodrostat in patients with Cushing's disease.The multicenter, 48-week, Phase III LINC 4 clinical trial had an optional extension period that was initially intended to continue to week 96. Patients could continue in the extension until a managed-access program or alternative treatment became available locally, or until a protocol amendment was approved at their site that specified that patients should come for an end-of-treatment visit within 4 weeks or by week 96, whichever occurred first. Study outcomes assessed in the extension included: mean urinary free cortisol (mUFC) response rates; changes in mUFC, serum cortisol and late-night salivary cortisol (LNSC); changes in cardiovascular and metabolic-related parameters; blood pressure, waist circumference and weight; changes in physical manifestations of Cushing's disease; changes in patient-reported outcomes for health-related quality of life; changes in tumor volume; and adverse events. Results were analyzed descriptively; no formal statistical testing was performed.Of 60 patients who entered, 53 completed the extension, with 29 patients receiving osilodrostat for more than 96 weeks (median osilodrostat duration: 87.1 weeks). The proportion of patients with normalized mUFC observed in the core period was maintained throughout the extension. At their end-of-trial visit, 72.4% of patients had achieved normal mUFC. Substantial reductions in serum cortisol and LNSC were also observed. Improvements in most cardiovascular and metabolic-related parameters, as well as physical manifestations of Cushing's disease, observed in the core period were maintained or continued to improve in the extension. Osilodrostat was generally well tolerated; the safety profile was consistent with previous reports.Osilodrostat provided long-term control of cortisol secretion that was associated with sustained improvements in clinical signs and physical manifestations of hypercortisolism. Osilodrostat is an effective long-term treatment for patients with Cushing's disease.ClinicalTrials.gov, identifier NCT02180217.Copyright © 2023 Gadelha, Snyder, Witek, Bex, Belaya, Turcu, Feelders, Heaney, Paul, Pedroncelli and Auchus.