Pharmacokinetics and Pharmacodynamics of Repository Corticotropin Injection Compared With Synthetic ACTH1-24 Depot and Methylprednisolone in Healthy Subjects.

Abstract

Repository corticotropin injection (RCI; Acthar Gel) is a naturally sourced complex mixture of adrenocorticotropic hormone (ACTH) analogs and other pituitary peptides. This phase 1, single-center, open-label, randomized parallel study directly compared the pharmacokinetics and pharmacodynamics of RCI and synthetic ACTH1-24 depot. Methylprednisolone was included to estimate the steroidogenic exposure of RCI and synthetic ACTH1-24 depot when used to treat nephrotic syndrome. A total of 48 healthy subjects aged 18 to 50 years were randomly assigned 1:1:1 to RCI (80\xa0IU subcutaneously twice weekly on study days 1 and 4), synthetic ACTH1-24 depot (1 mg subcutaneously twice weekly on study days 1 and 4), or methylprednisolone (32 mg orally once daily on study days 1 through 6). After 2 doses, RCI induced about 5-fold lower free cortisol exposure and an estimated 4-fold lower steroidogenic exposure than synthetic ACTH1-24 depot. The lower endogenous cortisol response of RCI was achieved despite higher observed mean plasma concentrations of N25-deamidated porcine ACTH1-39 (the pharmacokinetic marker for RCI) than of ACTH1-24 . The different pharmacodynamic properties demonstrated by RCI and synthetic ACTH1-24 depot in this study suggest that these products in the ACTH class are not interchangeable.