Comparison Of Steroidogenic Exposure Following The Administration Of Repository Corticotropin Injection With A Synthetic Acth(1-24) Depot And Methylprednisolone In Healthy Subjects

The pharmacokinetics (PK) and pharmacodynamics (PD) of clinically relevant doses of repository corticotropin injection (Acthar Gel) and synthetic ACTH(1-24) depot have not been fully characterized. We compared the steroidogenic exposure of repository corticotropin injection and synthetic ACTH(1-24) depot in healthy adults at therapeutic doses using data from 2 separate phase 1 studies. Subjects were randomly assigned to repository corticotropin injection 40 or 80 IU subcutaneously twice weekly or 80 IU subcutaneously 3 times weekly for 15 days or to daily synthetic ACTH(1-24) depot doses of 0.5 mg subcutaneously, 0.75 mg subcutaneously, 1 mg subcutaneously, or 1 mg intramuscularly for 5 days. A population PK/PD model was developed to simulate the free cortisol exposure of a clinically relevant dose of synthetic ACTH(1-24) depot (1 mg subcutaneously twice weekly). Study drug doses were converted to methylprednisolone-equivalent doses using the steroidogenic exposure of methylprednisolone 16 mg daily as a conversion factor. Doses were also converted to prednisone equivalents using a coefficient of 1.25. These analyses revealed that the steroidogenic exposure of repository corticotropin injection at clinically relevant doses was substantially lower than that for synthetic ACTH(1-24) depot. The 3 repository corticotropin injection regimens were equivalent to approximately 5, 8, and 16 mg of daily prednisone, respectively. On the basis of simulated free cortisol exposure, synthetic ACTH(1-24) depot 1 mg subcutaneously twice weekly was comparable to 57 mg of daily prednisone. These results suggest that repository corticotropin injection has pharmacological effects that cannot be considered identical to synthetic ACTH(1-24) depot.