Pharmaceutical formulations containing relacorilant, a heteroaryl-ketone fused azadecalin compound

Patent metadata

Field	Value
Publication number	US-11925626-B2
Application number	US-202217950902-A
Country	US
Kind code	B2
Filing date	Sep 22, 2022
Priority date	Dec 19, 2018
Publication date	Mar 12, 2024
Grant date	Mar 12, 2024

Abstract

Disclosed herein are novel formulations containing relacorilant ((R)-(1-(4-fluorophenyl)-6-(1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone) that are suitable for administration, including oral administration, to patients suffering from disorders amenable to treatment by glucocorticoid receptor modulators (GRMs). Single unit dosage forms comprise softgel capsules containing these formulations. Such softgel capsules may contain, e.g., relacorilant formulations containing 25 milligrams (mg), 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, or other amounts of relacorilant. These novel formulations and single unit dosage forms may be used to treat diseases and disorders including Cushing's syndrome, Cushing's Disease, and other disorders.

First claim

We claim:

1. A formulation for oral administration of relacorilant, (R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone, which has the following structure:

the formulation comprising:
about 18 to 22% relacorilant;
about 56% to 64% surfactant, wherein said surfactant is lauroyl polyoxyl glyceride, and
about 18% to 22% solubilizer, wherein said solubilizer is propylene glycol monocaprylate,
wherein said percentages are weight percent.

2. The formulation of claim 1 , further including the antioxidant selected from butylated hydroxytoluene (BHT).

3. The formulation of claim 2 , wherein the formulation comprises about 0.02% antioxidant by weight of the formulation.

4. The formulation of claim 2 , consisting of 20% relacorilant, 59.98% surfactant, 20% solubilizer, and 0.02% antioxidant.

5. The formulation of claim 4 , consisting of 25 mg relacorilant, 74.975 mg surfactant, 25 mg solubilizer, and 0.025 mg antioxidant.

6. The formulation of claim 4 , consisting of 50 mg relacorilant, 149.95 mg surfactant, 50 mg solubilizer, and 0.05 mg antioxidant.

7. The formulation of claim 4 , consisting of 100 mg relacorilant, 299.9 mg surfactant, 100 mg solubilizer, and 0.1 mg antioxidant.

8. The formulation of claim 4 , consisting of 150 mg relacorilant, 349.85 mg surfactant, 150 mg solubilizer, and 0.15 mg antioxidant.

9. The formulation of claim 4 , consisting of 200 mg relacorilant, 599.8 mg surfactant, 200 mg solubilizer, and 0.2 mg antioxidant.

10. The formulation of claim 4 , consisting of 300 mg relacorilant, 899.7 mg surfactant, 300 mg solubilizer, and 0.3 mg antioxidant.

11. The formulation of claim 4 , consisting of 400 mg relacorilant, 1199.6 mg surfactant, 400 mg solibilizer, and 0.4 mg antioxidant.

12. The formulation of claim 4 , consisting of 500 mg relacorilant, 1499.5 mg surfactant, 500 mg solubilizer, and 0.5 mg antioxidant.

13. consisting essentially of a softgel capsule containing a relacorilant formulation consisting of 20% relacorilant, 59 .98% surfactant, wherein said surfactant is lauroyl polyoxyl glyceride, and 20% solubilizer, wherein said solubilizer is propylene glycol monocaprylate, and 0.02% antioxidant, wherein said antioxidant is butylated hydroxytoluene (BHT), wherein said percentages are weight percentages.

14. The unit dose for oral administration of relacorilant of claim 13 , said softgel capsule containing a relacorilant formulation consisting of 25 mg relacorilant, 74.975 mg surfactant, 25 mg solubilizer, and 0.025 mg antioxidant.

15. The unit dose for oral administration of relacorilant of claim 13 , said softgel capsule containing a relacorilant formulation consisting of 50 mg relacorilant, 149.95 mg surfactant, 50 mg solubilizer, and 0.05 mg antioxidant.

16. The unit dose for oral administration of relacorilant of claim 13 , said softgel capsule containing a relacorilant formulation consisting of 100 mg relacorilant, 299.9 mg surfactant, 100 mg solubilizer, and 0.1 mg antioxidant.

17. The unit dose for oral administration of relacorilant of claim 13 , said softgel capsule containing a relacorilant formulation consisting of 150 mg relacorilant, 349.85 mg surfactant, 150 mg solubilizer, and 0.15 mg antioxidant.

18. The unit dose for oral administration of relacorilant of claim 13 , said softgel capsule containing a relacorilant formulation consisting of 200 mg relacorilant, 599.8 mg surfactant, 200 mg solubilizer, and 0.2 mg antioxidant.

19. The unit dose for oral administration of relacorilant of claim 13 , said softgel capsule containing a relacorilant formulation consisting of 300 mg relacorilant, 899.7 mg surfactant, 300 mg solubilizer, and 0.3 mg antioxidant.

20. The unit dose for oral administration of relacorilant of claim 13 , said softgel capsule containing a relacorilant formulation consisting of 400 mg relacorilant, 1199.6 mg surfactant, 400 mg solubilizer, and 0.4 mg antioxidant.

21. The unit dose for oral administration of relacorilant of claim 13 , said softgel capsule containing a relacorilant formulation consisting of 500 mg relacorilant, 1499.5 mg surfactant, 500 mg solubilizer, and 0.5 mg antioxidant.

Assignees

• Corcept Therapeutics Inc

Inventors

• Scott Ian
• Lemons Travis
• Chia Yip-Fong

Classifications

• A61K31/437 Primary

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K9/4808

  characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release (capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084) · CPC title

• A61K9/4866

  Organic macromolecular compounds · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title