Trial results for the long-term safety study of elagolix in combination with estradiol/norethindrone acetate for heavy menstrual bleeding associated with uterine fibroids were posted on ClinicalTrials.gov on 2025-07-22. The study reported that 203 participants in the active treatment group experienced adverse events, compared to 83 participants in the placebo group for one measurement of adverse events.
Background
Elagolix, marketed as Orilissa and Oriahnn (when combined with estradiol and norethindrone acetate), is used for the management of conditions like heavy menstrual bleeding associated with uterine fibroids. This specific study investigated the long-term safety profile of the combination therapy in premenopausal women.
Trial design
The study (NCT03271489) was a Phase 3b, randomized, multicenter trial that enrolled 478 participants. It evaluated the long-term safety of elagolix in combination with estradiol/norethindrone acetate (E2/NETA) for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. The study design included a double-blind period for the first 12 months, followed by an open-label period for an additional 36 months. The primary focus of the study was to evaluate safety.
Key results
The trial results reported on the number of participants experiencing adverse events and bone mineral density recovery. For the outcome of "Number of Participants With Adverse Events (AEs)":
- In one measurement, 203 participants in the Elagolix Plus Estradiol (E2)/Norethindrone Acetate (NETA) group experienced adverse events, compared to 83 participants in the Placebo group.
- In another measurement, 124 participants in the Elagolix Plus Estradiol (E2)/Norethindrone Acetate (NETA) group experienced adverse events, compared to 59 participants in the Placebo group.
- A third measurement showed 22 participants in the Elagolix Plus Estradiol (E2)/Norethindrone Acetate (NETA) group experienced adverse events, compared to 6 participants in the Placebo group.
For the outcome of "Bone Mineral Density (BMD) Recovery After up to 48 Months of Treatment":
- In one measurement, 24 participants in the Elagolix Plus Estradiol (E2)/Norethindrone Acetate (NETA) group showed BMD recovery, compared to 10 participants in the Placebo group.
- In another measurement, 8 participants in the Elagolix Plus Estradiol (E2)/Norethindrone Acetate (NETA) group showed BMD recovery, compared to 2 participants in the Placebo group.
- A third measurement showed 3 participants in the Elagolix Plus Estradiol (E2)/Norethindrone Acetate (NETA) group showed BMD recovery, compared to 2 participants in the Placebo group.
What this means
The results from this long-term safety study provide data on the adverse event profile and bone mineral density recovery for elagolix combination therapy in premenopausal women with heavy menstrual bleeding associated with uterine fibroids. The reported participant counts indicate that adverse events were observed in both the active treatment and placebo groups, with a higher number of participants experiencing adverse events in the elagolix combination group across various measurements. Data on bone mineral density recovery was also collected over the study period.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03271489, titled "Long-Term Safety Study of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women," were posted on 2025-07-22 on clinicaltrials.gov.