Comparison of Steroidogenic Exposure Following the Administration of Repository Corticotropin Injection With a Synthetic ACTH<sub>1‐24</sub> Depot and Methylprednisolone in Healthy Subjects
Bibliographic record
Abstract
Abstract 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".