# US 11,992,479 B2 · R-fadrozole for use in the treatment of aldostonerism > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,992,479 B2 - Document ID: US11992479B2 - Status: Granted - Kind: B2 - Application number: 17/052,359 - Filed: 2019-05-02 - Published: 2021-06-10 - Granted: 2024-05-28 - Earliest claimed: 2018-05-03 - Assignees: Damian Pharma AG - Applicants: Damian Pharma AG - Inventors: Ronald Edward Steele; Christoph Schumacher - Web page: https://patentgrep.com/patent/US11992479B2 ## CPC - A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline - A61K 9/2004: {Excipients; Inactive ingredients} - A61P 5/00: Drugs for disorders of the endocrine system - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 9/12: Antihypertensives - A61P 13/12: of the kidneys - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to a composition for use in the treatment of a disease or disorder, wherein said disease or disorder is preferably a disease or disorder in which aldosterone overexposure contributes to the symptoms of said disease or disorder, said composition comprises a compound which is (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine or a pharmaceutically acceptable salt thereof, wherein preferably said compound is (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazolium[1,5-a]pyridine dihydrogen phosphate, and wherein said compound has an enantiomeric excess (ee) of the (R) form higher than or equal to 97%, and wherein said composition is administered once daily to a subject in need thereof. The invention further relates to a pharmaceutical composition comprising a daily dosage of said compound in a fixed-unit dosage form and to a combination comprising (i) said pharmaceutical composition or said compound; and (ii) instructions for administration of said pharmaceutical composition or said compound once per day. ## Claims ### Claim 1 A method of treating a disease or disorder selected from primary aldosteronism and secondary aldosteronism in human a subject in need thereof, the method comprising orally administering once daily to said subject a therapeutically effective amount of a composition comprising 4 mg or 8 mg of a compound which is R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine dihydrogen phosphate, wherein said compound has an enantiomeric excess (ee) of the (R) form higher than or equal to 99%. ### Claim 2 (depends on 1) The method according to claim 1, wherein an elimination half-life (T1/2) of said compound upon administration of one 4mg or 8mg daily dose to the subject is longer than 8h, as measured in a blood sample of the subject obtained at 8, 12, 16 or 24 hours post-dose. ### Claim 3 (depends on 1) The method according to claim 1, wherein said (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazolium[1,5-a]pyridine dihydrogen phosphate is a crystalline form I of (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazolium [1,5-a]pyridine dihydrogen phosphate, wherein said crystalline form I has an X-ray powder diffraction pattern comprising the following 20 values measured using CuKα radiation: 19.504; 21.919 and 24.159, wherein each peak may vary by ±0.5. ### Claim 4 (depends on 1) The method according to claim 1, wherein said disease or disorder is primary aldosteronism. ### Claim 5 (depends on 1) The method of claim 1, wherein said disease or disorder is secondary aldosteronism. ### Claim 6 (depends on 1) The method according to claim 1, wherein said compound has an enantiomeric excess (ee) of the (R) form higher than or equal to 99.5%. ### Claim 7 (depends on 1) The method according to claim 1, wherein said compound has an enantiomeric excess (ee) of the (R) form higher than or equal to 99.8%. ### Claim 8 (depends on 1) The method according to claim 1, wherein said compound has an enantiomeric excess (ee) of the (R) form higher than or equal to 99.9%. ### Claim 9 (depends on 1) The method according to claim 1, wherein said disease or disorder is primary aldosteronism, and wherein said composition comprises 8 mg of the compound. ### Claim 10 (depends on 1) The method according to claim 1, wherein said disease or disorder is secondary aldosteronism, and wherein said composition comprises 8 mg of the compound. ### Claim 11 (depends on 1) The method according to claim 1, wherein said disease or disorder is primary aldosteronism, and wherein said composition comprises 4 mg of the compound. ### Claim 12 (depends on 1) The method according to claim 1, wherein said disease or disorder is secondary aldosteronism, and wherein said composition comprises 4 mg of the compound. ### Claim 13 A method of treating primary aldosteronism in a human subject in need thereof, the method comprising orally administering to the subject 4 mg of the compound (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazolium[1,5-a]pyridine dihydrogen phosphate, once daily, wherein said compound has an enantiomeric excess (ee) of the (R) form higher than or equal to 99%. ### Claim 14 A method of treating primary aldosteronism in a human subject in need thereof, the method comprising orally administering to the subject 8 mg of the compound (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazolium[1,5-a]pyridine dihydrogen phosphate, once daily, wherein said compound has an enantiomeric excess (ee) of the (R) form higher than or equal to 99%. ### Claim 15 (depends on 13) The method of claim 13, wherein the human subject is a pediatric patient. ### Claim 16 (depends on 13) The method of claim 13, wherein the human subject is a woman of child bearing potential. ### Claim 17 (depends on 14) The method of claim 14, wherein the human subject is a pediatric patient. ### Claim 18 (depends on 14) The method of claim 14, wherein the human subject is a woman of child bearing potential.