# US 2021/0275527 A1 · Methods of Administering Elagolix > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0275527 A1 - Document ID: US20210275527A1 - Status: Published application - Kind: A1 - Application number: 17/004,817 - Filed: 2020-08-27 - Published: 2021-09-09 - Earliest claimed: 2020-03-05 - Assignees: AbbVie Inc. - Applicants: AbbVie Inc. - Inventors: Farah N. Ali; Sheetal P. Dharia; Nael M. Mostafa; Ahmed Nader; Akshanth R. Polepally; Mohamad Shebley - Web page: https://patentgrep.com/patent/US20210275527A1 ## CPC - A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 31/565: not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol - A61K 31/57: substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone - 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) ## Abstract The present disclosure relates to the use of GnRH receptor antagonists for the treatment of endometriosis, uterine fibroids, polycystic ovary syndrome (PCOS), or adenomyosis. In particular, the present disclosure describes methods for treating such gynecological disorders, where the methods involve administration of elagolix and may further involve co-administration of a CYP2B6 substrate (e.g., bupropion) or a CYP2C19 substrate (e.g., omeprazole). ## Claims ### Claim 1 A method for treating a gynecological disorder, the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein the patient concomitantly receives bupropion, wherein the bupropion is administered without an adjustment to a recommended bupropion dosing schedule. ### Claim 2 (depends on 1) The method of claim 1, wherein the recommended bupropion dosing schedule comprises (i) a 100 mg dose administered twice per day, (ii) a 100 mg dose administered three times per day, and/or (iii) a 150 mg dose administered three times per day for an immediate-release bupropion formulation. ### Claim 3 (depends on 1) The method of claim 1, wherein the recommended bupropion dosing schedule comprises (i) a 150 mg dose administered once per day, and/or (ii) a 200 mg dose administered once per day for an extended-release bupropion formulation. ### Claim 4 A method for treating a gynecological disorder, the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein the patient concomitantly receives omeprazole, wherein the omeprazole is administered without an adjustment to a recommended omeprazole dosing schedule. ### Claim 5 (depends on 4) The method of claim 4, wherein the recommended omeprazole dosing schedule comprises (i) a 20 mg dose administered once per day and/or (ii) a 40 mg dose administered once per day. ### Claim 6 A method for treating a gynecological disorder, the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein the patient concomitantly receives omeprazole for a pathologic hypersecretory condition, wherein the omeprazole is administered according to a modified omeprazole dosing schedule, such modified omeprazole dosing schedule comprising a reduced omeprazole dose and/or a reduced frequency of omeprazole administration relative to a recommended omeprazole dosing schedule for pathologic hypersecretory conditions. ### Claim 7 (depends on 6) The method of claim 6, wherein the recommended omeprazole dosing schedule for pathologic hypersecretory conditions comprises (i) a 60 mg dose administered once per day and/or (ii) a 120 mg dose administered three times per day. ### Claim 8 (depends on 6) The method of claim 6, wherein the modified omeprazole dosing schedule provides (i) an omeprazole AUCinf ratio comparing (A) omeprazole AUCinf when co-administered with elagolix to (B) omeprazole AUCinf when administered alone between about 0.5 and about 2.0 and/or (ii) an omeprazole Cmax ratio comparing (A) omeprazole Cmax when co-administered with elagolix to (B) omeprazole Cmax when administered alone between about 0.5 and about 2.0. ### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8) The method of any one of claims 1-8, wherein the gynecological disorder is endometriosis and the method is for the management of moderate to severe pain associated with endometriosis. ### Claim 10 (depends on 9) The method of claim 9, wherein elagolix sodium is administered in an amount equivalent to 150 mg of elagolix free acid once daily or elagolix sodium is administered in an amount equivalent to 200 mg of elagolix free acid twice daily. ### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8) The method of any one of claims 1-8, wherein the gynecological disorder is uterine leiomyomas (fibroids) and the method is for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids). ### Claim 12 (depends on 11) The method of claim 11, wherein elagolix sodium is administered in an amount equivalent to 300 mg of elagolix free acid twice daily. ### Claim 13 (depends on 12) The method of claim 12, wherein elagolix sodium is administered with an estrogen and progestin combination. ### Claim 14 (depends on 13) The method of claim 13, wherein the estrogen and progestin combination comprises estradiol and norethindrone acetate. ### Claim 15 A method for management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids), the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein elagolix sodium is administered in an amount equivalent to 300 mg of elagolix free acid twice daily; wherein the patient receives a dose of 150 mg of bupropion; and wherein: (i) a bupropion Cmax ratio, which compares (A) bupropion Cmax when co-administered in the presence of elagolix to (B) bupropion Cmax when administered alone, is 1.246 with a 90% confidence interval of 1.104-1.407; and/or (ii) a bupropion AUCinf ratio, which compares (A) bupropion AUCinf when co-administered in the presence of elagolix to (B) bupropion AUCinf when administered alone, is 0.965 with a 90% confidence interval of 0.910-1.023. ### Claim 16 A method for management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids), the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein elagolix sodium is administered in an amount equivalent to 300 mg of elagolix free acid twice daily; wherein the patient receives a dose of 40 mg of omeprazole; and wherein: (i) an omeprazole Cmax ratio, which compares (A) omeprazole Cmax when co-administered in the presence of elagolix to (B) omeprazole Cmax when administered alone, is 1.95 with a 90% confidence interval of 1.50-2.53; and/or (ii) an omeprazole AUCinf ratio, which compares (A) omeprazole AUCinf when co-administered in the presence of elagolix to (B) omeprazole AUCinf when administered alone, is 1.78 with a 90% confidence interval of 1.39-2.27. ### Claim 17 (depends on 15, 16) The method of claim 15 or claim 16, wherein elagolix sodium is administered with an estrogen and progestin combination. ### Claim 18 (depends on 17) The method of claim 17, wherein the estrogen and progestin combination comprises estradiol and norethindrone acetate. ### Claim 19 A method for management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids), the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein elagolix sodium is administered in an amount equivalent to 300 mg of elagolix free acid twice daily; further wherein said patient has a co-morbid Zollinger-Ellison syndrome and said patient receives: (a) a reduced starting daily dose of less than 60 mg of omeprazole administered once a day; (b) a reduced daily dose of less than 80 mg of omeprazole administered once a day, twice a day or three times a day; or (c) a reduced daily dose of less than 120 mg of omeprazole administered three times a day. ### Claim 20 A method for management of moderate to severe pain associated with endometriosis, the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein elagolix sodium is administered in an amount equivalent to 150 mg of elagolix free acid once a day or 200 mg of elagolix free acid twice a day; further wherein said patient has a co-morbid Zollinger-Ellison syndrome and said patient receives: (a) a reduced starting daily dose of less than 60 mg of omeprazole administered once a day; (b) a reduced daily dose of less than 80 mg of omeprazole administered once a day, twice a day or three times a day; or (c) a reduced daily dose of less than 120 mg of omeprazole administered three times a day. ### Claim 21 (depends on 19, 20) The method of any one of the claims 19 or 20, wherein the reduced starting daily dose of less than 60 mg of omeprazole is greater than 10 mg and less than 60 mg of omeprazole administered once a day. ### Claim 22 (depends on 19, 20) The method of any one of the claims 19 or 20, wherein the daily reduced dose of 120 mg of omeprazole three times a day is: (a) 120 mg of omeprazole administered two times a day or 120 mg of omeprazole administered once a day; (b) between 10 mg to less than 120 mg of omeprazole administered three times a day; (c) between 10 mg to less than 120 mg of omeprazole administered two times a day; or (d) between 10 mg to less than 120 mg of omeprazole administered once a day. ### Claim 23 A method for management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids), the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein elagolix sodium is administered in an amount equivalent to 300 mg of elagolix free acid twice daily; further wherein said patient has a co-morbid Zollinger-Ellison syndrome and said patient receives a drug that is metabolized by CYP2C19 pathway, such that said drug is (a) lansoprazole, and the reduced daily dose of lansoprazole is less than 60 mg administered once a day; (b) omeprazole, and the reduced daily dose of omeprazole is between 10 mg to less than 360 mg administered daily; (c) pantoprazole, and the reduced daily dose of pantoprazole is less than 40 mg twice a day; (d) rabeprazole, and the reduced daily dose of rabeprazole is less than 60 mg administered once a day; or esomoprazole, and the reduced daily dose of esomoprazole is less than 40 mg twice a day. ### Claim 24 A method for management of moderate to severe pain associated with endometriosis, the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein elagolix sodium is administered in an amount equivalent to 150 mg of elagolix free acid once a day or 200 mg of elagolix free acid twice a day; further wherein said patient has a co-morbid Zollinger-Ellison syndrome and said patient receives a drug that is metabolized by CYP2C19 pathway, such that said drug is: (a) lansoprazole, and the reduced daily dose of lansoprazole is less than 60 mg administered once a day; (b) omeprazole, and the reduced daily dose of omeprazole is between 10 mg to less than 360 mg administered daily; (c) pantoprazole, and the reduced daily dose of pantoprazole is less than 40 mg twice a day; (d) rabeprazole, and the reduced daily dose of rabeprazole is less than 60 mg administered once a day; or (e) esomoprazole, and the reduced daily dose of esomoprazole is less than 40 mg twice a day.