Methods for administering corticosteroids
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Assignees
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Publication Number
US-12220412-B2
Publication Date
2025-02-11
Expiration Date
Abstract
Provided is a method for administering a corticosteroid to a patient in need thereof, comprising: determining a target threshold for the ratio of urinary (tetrahydrocortisol+allotetrahydrocortisol) to urinary tetrahydrocortisone for the patient; and administering an HSD1 inhibitor to the patient. Also provided is a method for reducing or preventing the side effects associated with corticosteroid administration to a patient in need thereof, comprising: determining a target threshold for the ratio of urinary (tetrahydrocortisol+allotetrahydrocortisol) to urinary tetrahydrocortisone for the patient; and administering an HSD1 inhibitor to the patient.
Core Innovation
A method is described for administering a corticosteroid to a patient who is in need thereof while also administering an HSD-1 inhibitor. The method determines a target threshold of 0.2 for the ratio of urinary (tetrahydrocortisol+allotetrahydrocortisol) to urinary tetrahydrocortisone for the patient, and the HSD-1 inhibitor is administered to maintain or reduce the patient’s urinary ratio below the target threshold.
The corticosteroid is not prednisone. The HSD-1 inhibitor includes 4-{5-[1-(4-chloro-2,6-difluorophenoxy)-1-methylethyl]-4-methyl-4H-1,2,4-triazol-3-yl-3-fluorobenzamide (Compound A) or a pharmaceutically acceptable salt thereof, and the first dose is administered for a first time period so that the administration is effective to maintain or reduce the patient’s urinary ratio below the target threshold.
The disclosure further describes maintaining or reducing the urinary ratio using target thresholds and related criteria, including alternatives to urinary ratios in the broader disclosure. It also describes selection among HSD1 inhibitors including Compound A, Compound B, AMG 221, and Xanamem, selection of corticosteroid types and routes, and risk-factor considerations tied to corticosteroid side effects. Clinical and translational evidence is described for Compound A, including urinary ratio reduction, a population PK model, PET-based brain HSD1 occupancy, simulated dosing schemes, and preclinical reversal of corticosteroid-induced behavioral effects.
Claims Coverage
The document includes one independent claim directed to a method of co-administering a non-prednisone corticosteroid with an HSD-1 inhibitor. The independent claim is anchored by a patient-specific urinary ratio target threshold and by administering Compound A at a first dose and first time period to maintain or reduce the urinary ratio below the threshold.
Urinary ratio target threshold for HSD-1 co-administration
Determining a target threshold of 0.2 for the ratio of urinary (tetrahydrocortisol+allotetrahydrocortisol) to urinary tetrahydrocortisone for the patient, and administering an HSD-1 inhibitor to a patient who is being administered a corticosteroid, wherein the administration is effective to maintain or reduce the patient’s urinary ratio below the target threshold.
Non-prednisone corticosteroid with HSD-1 inhibitor
Administering a corticosteroid to a patient in need thereof, wherein the corticosteroid is not prednisone, while administering an HSD-1 inhibitor.
Compound A HSD-1 inhibitor at a first dose and first time period
Administering the HSD-1 inhibitor as 4-{5-[1-(4-chloro-2,6-difluorophenoxy)-1-methylethyl]-4-methyl-4H-1,2,4-triazol-3-yl-3-fluorobenzamide (Compound A) or a pharmaceutically acceptable salt thereof, at a first dose for a first time period so that the administration is effective to maintain or reduce the patient’s urinary ratio below the target threshold.
Overall, the claim coverage centers on co-administering a non-prednisone corticosteroid with an HSD-1 inhibitor where patient monitoring is based on maintaining or reducing a urinary ratio of (tetrahydrocortisol+allotetrahydrocortisol) to tetrahydrocortisone below a specified target threshold, using Compound A or a salt thereof to achieve that ratio control.
Stated Advantages
Maintain or reduce the patient’s urinary ratio of urinary (tetrahydrocortisol+allotetrahydrocortisol) to urinary tetrahydrocortisone at a level below the target threshold.
Reduce or prevent corticosteroid side effects, including HPA suppression and metabolic and other corticosteroid-related adverse effects described in the disclosure.
Documented Applications
Administering the described corticosteroid and HSD-1 inhibitor co-treatment to treat selected diseases or disorders, including multiple specified vasculitides and related conditions such as giant cell arteritis and polymyalgia rheumatica, among others listed in the disclosure.
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