Modified-release Hydrocortisone Therapy as a Treatment for CAH

改良释放氢化可的松疗法治疗 CAH

• 批准号: 10266528
• 负责人: Deborah Merke
• 金额: $ 0.2万
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10266528
• 关键词: 21-hydroxylase deficiency; Adrenal Cortex Diseases; Adrenal Glands; Adult; Aldosterone; Androgens; Body Composition; Body mass index; Circadian Rhythms; Clinical; Data Analyses; Dexamethasone; Dose; Failure; Fatty acid glycerol esters; Female; Formulation; Glucocorticoids; Growth; Hormone replacement therapy; Hydrocortisone; Infertility; International; Metabolic syndrome; Multicenter Studies; Obesity; Osteoporosis; Patient-Focused Outcomes; Patients; Phase; Phase III Clinical Trials; Physiological; Prednisone; Thinness; Virilism; conventional therapy; design; improved; male; novel; pharmacokinetics and pharmacodynamics; phase 2 study; phase 3 study

A Phase 2, crossover pharmacokinetic and pharmacodynamic study in 16 adults (8 females) with classic CAH, comparing a newly-developed modifed-release formulation of hydrocortisone with conventional hydrocortisone, was completed. This newly developed formulation of hydrocortisone, Chronocort, was designed to mimic the normal cortisol circadian rhythm. Twice daily Chronocort was found to approximate physiologic cortisol secretion. Compared to conventional therapy at baseline, Chronocort at 6 months showed improved androgen levels throughout the day and this lowering of androgens was achieved with a lower or similar average daily glucocorticoid dose. Although there were no significant changes in body mass index, studies of body composition showed an increase in lean mass (females) and a decrease in fat mass (males). This novel hydrocortisone formulation represents a potential new treatment approach for patients with CAH and is currently being studied in an international multi-center phase 3 clinical trial. The phase 3 study is now completed and data analysis is underway.

对 16 名患有经典 CAH 的成年人（8 名女性）进行的 2 期交叉药代动力学和药效学研究已完成，该研究将新开发的氢化可的松缓释制剂与传统氢化可的松进行比较。 这种新开发的氢化可的松制剂 Chronocort 旨在模仿正常的皮质醇昼夜节律。每天两次 Chronocort 被发现接近生理皮质醇分泌。 与基线时的常规治疗相比，Chronocort 在 6 个月时表现出全天雄激素水平的改善，并且雄激素的降低是通过较低或相似的平均每日糖皮质激素剂量实现的。尽管体重指数没有显着变化，但身体成分研究显示去脂体重（女性）增加，脂肪量（男性）减少。 这种新型氢化可的松制剂代表了 CAH 患者的一种潜在的新治疗方法，目前正在一项国际多中心 3 期临床试验中进行研究。第三阶段研究现已完成，数据分析正在进行中。