Methods of treating heavy menstrual bleeding

Abstract

The present invention relates to the method of treating heavy menstrual bleeding in a subject with or without uterine fibroids and in need of treatment by administering an effective amount of 4-((R)-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino)-butyric acid or a pharmaceutically acceptable salt thereof, in combination with estrogens and progestogens.

What is claimed is: 
     
         1 . A method of managing moderate to severe pain associated with endometriosis in a premenopausal adult human female patient, the method comprising:
 oral administration to the patient of 150 mg of 4-((R)-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino)-butyric acid, administered as a sodium salt (“elagolix”), and   continuing said oral administration once daily for a time period as needed to manage the moderate to severe pain associated with endometriosis;   wherein the method does not comprise administration of add-back therapy.   
     
     
         2 . The method of  claim 1 , wherein the time period does not exceed 24 months. 
     
     
         3 . The method of  claim 1 , wherein the method reduces dysmenorrhea and non-menstrual pelvic pain in the patient. 
     
     
         4 . The method of  claim 1 , wherein the method reduces dysmenorrhea and non-menstrual pelvic pain in the patient without an increase in use of a concomitant medication for the treatment of endometriosis-related pain by the patient. 
     
     
         5 . The method of  claim 4 , wherein the concomitant medication for the treatment of endometriosis-related pain is an analgesic. 
     
     
         6 . The method of  claim 5 , wherein the analgesic is an anti-inflammatory drug or an opioid. 
     
     
         7 . The method of  claim 1 , wherein the patient does not have osteoporosis. 
     
     
         8 . A method of managing moderate to severe pain associated with endometriosis in a premenopausal adult human female patient, the method comprising:
 providing a dosage form comprising 150 mg or 200 mg of 4-((R)-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino)-butyric acid as a sodium salt,   selecting a dosing regimen suitable to mitigate decreases in bone mineral density (BMD) in the patient, wherein the selected dosing regimen comprises once daily oral administration to the patient of the dosage form comprising 150 mg of 4-((R)-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino)-butyric acid as a sodium salt (“elagolix”) and wherein the selected dosing regimen does not comprise administration of add-back therapy, and   orally administering elagolix to the patient according to the selected dosing regimen for a time period as needed to manage the moderate to severe pain associated with endometriosis.   
     
     
         9 . The method of  claim 8 , wherein the time period does not exceed 24 months. 
     
     
         10 . The method of  claim 8 , wherein the method reduces dysmenorrhea and non-menstrual pelvic pain in the patient. 
     
     
         11 . The method of  claim 8 , wherein the method reduces dysmenorrhea and non-menstrual pelvic pain in the patient without an increase in use of a concomitant medication for the treatment of endometriosis-related pain by the patient. 
     
     
         12 . The method of  claim 11 , wherein the concomitant medication for the treatment of endometriosis-related pain is an analgesic. 
     
     
         13 . The method of  claim 12 , wherein the analgesic is an anti-inflammatory drug or an opioid. 
     
     
         14 . The method of  claim 8 , wherein the patient has a history of low-trauma fractures or a history of a condition associated with a decrease in BMD. 
     
     
         15 . The method of  claim 8 , wherein the method further comprises administration of supplementary calcium, vitamin D, or a combination thereof.