BACKGROUND: Endometriosis is a chronic, estrogen-dependent condition that causes 
dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, 
gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly 
full estrogen suppression in previous studies.
METHODS: We performed two similar, double-blind, randomized, 6-month phase 3 
trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects 
of two doses of elagolix - 150 mg once daily (lower-dose group) and 200 mg twice 
daily (higher-dose group) - as compared with placebo in women with surgically 
diagnosed endometriosis and moderate or severe endometriosis-associated pain. 
The two primary efficacy end points were the proportion of women who had a 
clinical response with respect to dysmenorrhea and the proportion who had a 
clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of 
these end points was measured as a clinically meaningful reduction in the pain 
score and a decreased or stable use of rescue analgesic agents, as recorded in a 
daily electronic diary.
RESULTS: A total of 872 women underwent randomization in Elaris EM-I and 817 in 
Elaris EM-II; of these women, 653 (74.9%) and 632 (77.4%), respectively, 
completed the intervention. At 3 months, a significantly greater proportion of 
women who received each elagolix dose met the clinical response criteria for the 
two primary end points than did those who received placebo. In Elaris EM-I, the 
percentage of women who had a clinical response with respect to dysmenorrhea was 
46.4% in the lower-dose elagolix group and 75.8% in the higher-dose elagolix 
group, as compared with 19.6% in the placebo group; in Elaris EM-II, the 
corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P<0.001 
for all comparisons). In Elaris EM-I, the percentage of women who had a clinical 
response with respect to nonmenstrual pelvic pain was 50.4% in the lower-dose 
elagolix group and 54.5% in the higher-dose elagolix group, as compared with 
36.5% in the placebo group (P<0.001 for all comparisons); in Elaris EM-II, the 
corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P=0.003 
and P<0.001, respectively). The responses with respect to dysmenorrhea and 
nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix 
had higher rates of hot flushes (mostly mild or moderate), higher levels of 
serum lipids, and greater decreases from baseline in bone mineral density than 
did those who received placebo; there were no adverse endometrial findings.
CONCLUSIONS: Both higher and lower doses of elagolix were effective in improving 
dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women with 
endometriosis-associated pain. The two doses of elagolix were associated with 
hypoestrogenic adverse effects. (Funded by AbbVie; Elaris EM-I and EM-II 
ClinicalTrials.gov numbers, NCT01620528 and NCT01931670 .).