Efficacy and Safety of Elagolix Versus Dienogest for Treatment of Moderate-to-Severe Endometriosis Pain: A Phase III, Multicentric, Double-Blind, Active-Controlled, Non-Inferiority Study.

OBJECTIVE

To compare the efficacy, safety and tolerability of elagolix with dienogest in women with moderate-to-severe endometriosis-associated pain.

DESIGN

A multicentre, double-blind, double-dummy, randomised, parallel-group, active-controlled, non-inferiority phase III study.

SETTING

Nineteen clinical centres across India.

STUDY POPULATION: Women (18-49 years) diagnosed with endometriosis and experiencing moderate-to-severe pain.

METHODS

Participants were randomised (1:1) to receive oral elagolix (150 mg once daily) or dienogest (2 mg once daily) for 24 weeks.

OUTCOME MEASURES: The primary outcome was change in endometriosis-related pain (Numeric Rating Scale [NRS]) from baseline to Day 85. Secondary outcomes included changes in NRS (Day 169), dysmenorrhoea, non-menstrual pelvic pain (NMPP) scores (Days 85 and 169), rescue medication use, patient global impression of change (PGIC), adverse events and bone mineral density.

RESULTS

Of 340 patients screened, 230 were randomised (115 per group). At Day 85, both arms showed similar reductions in NRS pain scores with a treatment difference of 0.04 (95% CI: -0.3, 0.37) [p = 0.9747] demonstrating non-inferiority as upper 95% CI was below pre-specified margin of 1.5. At Day 169, both arms showed comparable improvements in overall pain, dysmenorrhoea and NMPP from baseline (p = 0.9372, p = 0.8884, and p = 0.9616, respectively). Rescue medication use and PGIC were comparable between treatment arms. Adverse event incidence was similar (elagolix: 14.8%; dienogest: 19.1%), with no serious TEAEs or discontinuations. No significant bone mineral density changes were observed.

CONCLUSIONS

Elagolix demonstrated non-inferiority to dienogest with an acceptable safety and tolerability profile, supporting its use in managing endometriosis-associated pain.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: CTRI/2023/01/049292.