Patent SG-11201907854V-A (SG)
Title: Concomitant administration of glucocorticoid receptor modulators and cyp3a inhibitors
Inventor: BELANOFF JOSEPH K
IPC: A61K31/497
Filed: 2018-02-28
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 07 September 2018 (07.09.2018) WIP0 I PCT omit VIII °nolo VIII ioo im mown° oimIE (10) International Publication Number WO 2018/160775 Al (51) International Patent Classification: A61K 31/56 (2006.01) A61P 43/00 (2006.01) A61K 31/497 (2006.01) (21) International Application Number: PCT/US2018/020336 (22) International Filing Date: 28 February 2018 (28.02.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/465,772 01 March 2017 (01.03.2017) US 62/466,867 03 March 2017 (03.03.2017) US (71) Applicant: CORCEPT THERAPEUTICS, INC. [US/US]; 149 Commonwealth Drive, Menlo Park, Califor- nia 94025 (US). (72) Inventor: BELANOFF, Joseph K.; 149 Commonwealth Drive, Menlo Park, California 94025 (US). (74) Agent: WEBER, Kenneth A. et al.; Kilpatrick Townsend & Stockton LLP, Mailstop: IP Docketing - 22, 1100 Peachtree Street, Suite 2800, Atlanta, Georgia 30309 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (54) Title: CONCOMITANT ADMINISTRATION OF GLUCOCORTICOID RECEPTOR MODULATORS AND CYP3A INHIBI- TORS 3000 Ana ly te Plasma Concen tra t ion ( ng lm L) — e— Mifepristone — o— RU42633 —v— RU42698 RU42848 2500 - 2000 - 1500 - 1000 - 500 - N N O 00 O C llllllll I I I 14 21 28 Study Day FIG. 1 (57) : Applicant provides methods of treating diseases including Cushing's syndrome and hormone-sensitive cancers by con- comitant administration of a glucocorticoid receptor modulator (GRM) and steroidogenesis inhibitors, and by concomitant administra- tion of a GRM and CYP3A inhibitors. The GRM may be, e.g., mifepristone; the CYP3A inhibitors or steroidogenesis inhibitors (col- lectively \"inhibitors\") may be, e.g., ketoconazole or itraconazole. Inhibitors may cause toxicity or other serious adverse reactions; con- comitant administration of inhibitors with other drugs may increase the risk of such toxicity and adverse reactions due to the inhibitors and/or the other drugs. Applicant has surprisingly found that GRMs may be administered to subjects receiving inhibitors without in- creasing the risk of adverse reactions; for example, Applicant has found that mifepristone may be concomitantly administered with ke- toconazole or itraconazole, providing safe concomitant administration of the GRM and ketoconazole or itraconazole. In embodiments, [Continued on next page] WO 2018/160775 Al MIDEDIMOMOIDEIREEMOMOHINNEMOIMEN OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: — with international search report (Art. 21(3)) the GRM dose may be reduced during concomitant administration of the GRM with inhibitors.