Clinical Trials

Elagolix: CLINICAL TRIALS IN UTERINE FIBROIDS

The most recent Uterine Fibroids Phase IIb trial was a 24-week, randomized, double-blind, multicenter, placebo-controlled, two cohort design study that evaluated the safety and efficacy of two different elagolix treatment regimens (300 mg BID and 600 mg QD) alone and in combination with two different strengths of add-back therapy (estradiol/norethindrone acetate). It was conducted in approximately 567 premenopausal women, age 18 to 51, with heavy menstrual bleeding associated with uterine fibroids, at approximately 100 sites in the United States, Canada, Puerto Rico, Chile, and the United Kingdom.

Top-line results showed that all of the elagolix treatment arms, with and without add-back therapy, reduced heavy menstrual bleeding as compared to placebo (p<0.001). The study’s primary endpoint was a composite design where subjects had to achieve a menstrual blood loss (MBL) volume of less than 80 mL as well as a 50 percent or greater reduction in MBL volume from baseline at the final study month as measured by the alkaline hematin method.

Among the most common adverse events (AEs) were hot flush, headache, nausea, and vomiting. Some AEs such as hot flush were more frequent in the elagolix only treatment arms as compared to the placebo and elagolix with add-back therapy treatment arms. Reduction in bone mineral density associated with elagolix alone was attenuated when elagolix was co-administered with add-back therapy. Discontinuations due to AEs were slightly greater for the elagolix 600 mg once-daily (QD) treatment arms with and without add-back therapy as compared to elagolix 300mg twice-daily (BID) treatment arms with and without add-back therapy.

The Phase III program began in the first quarter of 2016 and includes two replicate, pivotal, six-month efficacy and safety studies followed by a six-month extension study. The studies will assess two 300 mg twice daily of elagolix both alone and in combination with add-back therapy (estradiol/norethindrone acetate). Each of the studies is expected to enroll 400 women with heavy menstrual bleeding due to uterine fibroids. The primary endpoint in Phase III studies is the same as that employed in the Phase IIb study; percent of subjects with reduction in uterine blood flow as measured by the alkaline hematin method at month six compared to baseline.