Phase 2, double-blind, randomized, placebo-controlled study of the safety and efficacy of elagolix in women with polycystic ovary syndrome

OBJECTIVE: Evaluate the efficacy and safety of elagolix, a GnRH antagonist, to treat polycystic ovarian syndrome (PCOS). DESIGN: A phase 2, multicenter, double-blind, randomized, placebo-controlled trial. SETTING: Outpatient and academic medical centers. PATIENT(S): One hundred fourteen women with PCOS (aged 18–35 years, body mass index 18.5–38 kg/m(2)). INTERVENTION(S): Patients were randomized 2:2:2:2:2:3 to elagolix (25 mg twice daily, 50 mg once daily, 75 mg twice daily, 150 mg once daily, and 300 mg twice daily) or placebo. MAIN OUTCOME MEASURE(S): The primary endpoint was menstrual cycle normalization (defined as 2 menstrual cycles 21–35 days in length during the 4-month treatment period). The secondary endpoint was change from baseline to week 1 in the area under the luteinizing hormone (LH) serum concentration-time curve (AUC). Additional endpoints included change from baseline in serum hormone levels. RESULT(S): No significant improvement in restoring normal menstrual cycles was observed in treated subjects; 3 of 114 patients met the primary endpoint. Six patients experienced progesterone elevations indicative of ovulation. The LH levels decreased from baseline to week 16, and LH AUC was significantly reduced from baseline to week 1 in all elagolix treatment groups (P<.1 vs placebo). Follicle-stimulating hormone (FSH) levels generally remained stable through week 16, with no significant differences in FSH AUCs. Serum estradiol and testosterone concentrations were consistently reduced from baseline in all elagolix dose groups compared with placebo. Adverse event rates were similar across treatment groups. CONCLUSION(S): Elagolix treatment did not normalize the ovulatory cycle in patients with PCOS. CLINICAL TRIAL REGISTRATION NUMBER: NCT03951077