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Pharmacokinetics and Pharmacodynamics of Repository Corticotropin Injection Compared With Synthetic ACTH_1-24 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 ACTH_1-24 depot. Methylprednisolone was included to estimate the steroidogenic exposure of RCI and synthetic ACTH_1-24 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 IU subcutaneously twice weekly on study days 1 and 4), synthetic ACTH_1-24 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 ACTH_1-24 depot. The lower endogenous cortisol response of RCI was achieved despite higher observed mean plasma concentrations of N25-deamidated porcine ACTH_1-39 (the pharmacokinetic marker for RCI) than of ACTH_1-24 . The different pharmacodynamic properties demonstrated by RCI and synthetic ACTH_1-24 depot in this study suggest that these products in the ACTH class are not interchangeable.

SUBMITTER: Poola N

PROVIDER: S-EPMC9290342 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Poola Nagaraju N Due Bryan B Wright Dale D Brooks Leah R LR Zaman Fahima F

Clinical pharmacology in drug development 20210915 4

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. ...[more]

PMID: 34528408

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Project description:BACKGROUND:Repository corticotropin injection (RCI) has regulatory approval for many indications, including symptomatic sarcoidosis. This large case series of patients with advanced symptomatic sarcoidosis treated with RCI describes patient characteristics, RCI utilization patterns, concomitant therapies, and physicians' assessments of treatment response. METHODS:Patients ⩾18 years with symptomatic sarcoidosis, treated with RCI in the previous 36 months, who had completed a course of RCI or received RCI for ⩾6 months at the time of data collection were included. RESULTS:The study included 302 patients (mean age, 51 years; 52%, women) with a mean 4.8 years since initial diagnosis of sarcoidosis. Most patients (76%) had extrapulmonary involvement, primarily in the skin (28%), joints (25%), heart (22%), and eyes (22%); 34% had multiple (⩾2) organ involvement. The mean duration of RCI treatment was 32.5 weeks, with 61.6% of patients continuing RCI therapy for ⩾6 months. The RCI utilization pattern indicated an individualized approach to therapy, with a higher starting dose associated with a shorter duration of therapy compared with a lower starting dose. The percentage of patients who used corticosteroids decreased from 61.3% during the 3 months before initiation of RCI to 12.9% 3 months after RCI therapy; the mean daily dose of corticosteroid decreased from 18.2 mg to 9.9 mg. The proportion of patients given <10 mg/day of prednisone increased from 21% before RCI use to 47% 3 months after RCI use. According to physicians' assessments of change in patients' health status after RCI therapy, overall status improved in 95% of patients, overall symptoms in 73%, lung function in 38%, and inflammation in 33%. CONCLUSIONS:The findings suggest that RCI is a viable treatment option for patients with advanced symptomatic sarcoidosis and provide insights on patient characteristics and practice patterns to help clinicians determine appropriate use. The reviews of this paper are available via the supplemental material section.

Dataset Information

Pharmacokinetics and Pharmacodynamics of Repository Corticotropin Injection Compared With Synthetic ACTH_1-24 Depot and Methylprednisolone in Healthy Subjects.

Publications

Pharmacokinetics and Pharmacodynamics of Repository Corticotropin Injection Compared With Synthetic ACTH<sub>1-24</sub> Depot and Methylprednisolone in Healthy Subjects.

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