Pharmacokinetics and Pharmacodynamics of Repository Corticotropin Injection Compared With Synthetic ACTH1-24 Depot and Methylprednisolone in Healthy Subjects. 2022

Nagaraju Poola, and Bryan Due, and Dale Wright, and Leah R Brooks, and Fahima Zaman
Mallinckrodt Pharmaceuticals, Hampton, New Jersey, USA.

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 IU 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.

UI MeSH Term Description Entries
D008775 Methylprednisolone A PREDNISOLONE derivative with similar anti-inflammatory action. 6-Methylprednisolone,Medrol,Metipred,Urbason,6 Methylprednisolone
D003366 Cosyntropin A synthetic peptide that is identical to the 24-amino acid segment at the N-terminal of ADRENOCORTICOTROPIC HORMONE. ACTH (1-24), a segment similar in all species, contains the biological activity that stimulates production of CORTICOSTEROIDS in the ADRENAL CORTEX. ACTH (1-24),Tetracosactide,Tetracosactrin,1-24-ACTH,1-24-Corticotropin,ACTH 1-24,Corticotropin (1-24)-Peptide,Corticotropin (1-24)-Tetracosapeptide,Cortosyn,Cortrosyn,Synthetic ACTH,Tetracosapeptide,ACTH, Synthetic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006854 Hydrocortisone The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol
D000324 Adrenocorticotropic Hormone An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP). ACTH,Adrenocorticotropin,Corticotropin,1-39 ACTH,ACTH (1-39),Adrenocorticotrophic Hormone,Corticotrophin,Corticotrophin (1-39),Corticotropin (1-39),Hormone, Adrenocorticotrophic,Hormone, Adrenocorticotropic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D064368 Healthy Volunteers Persons with no known significant health problems who are recruited to participate in research to test a new drug, device, or intervention as controls for a patient group. (from http://clinicalcenter.nih.gov/recruit/volunteers.html, accessed 2/14/2013) Healthy Participants,Healthy Subjects,Human Volunteers,Normal Volunteers,Healthy Participant,Healthy Subject,Healthy Volunteer,Human Volunteer,Normal Volunteer,Participant, Healthy,Participants, Healthy,Subject, Healthy,Subjects, Healthy,Volunteer, Healthy,Volunteer, Human,Volunteer, Normal,Volunteers, Human,Volunteers, Normal

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