SR-16234, a Novel Selective Estrogen Receptor Modulator for Pain Symptoms with Endometriosis: An Open-label Clinical Trial

Abstract

Background: SR-16234 is a selective estrogen receptor modulator (SERM) structurally different from approved SERM and has been reported to have estrogen receptor (ER) α antagonistic activity and strong affinity with a weak partial agonistic activity to ERβ receptor. SR-16234 showed strong inhibitory effects on transplanted endometrial cysts in the endometriosis model of rat and mouse. In this clinical trial, efficacy and safety of SR-16234 have been evaluated in endometriosis patients.

Methods: This trial was an open-label single arm clinical trial. Ten patients with dysmenorrhea and pelvic pain associated with endometriosis and adenomyosis were enrolled in this trial, and received 40 mg of SR-16234 once daily for 12 weeks. The primary endpoint was the visual analogue scale (VAS) of pelvic pain. The secondary endpoints included dysmenorrhea score, pelvic pain score, objective observations (stiffness of Douglas' pouch, limitation of uterine movement, size of ovarian chocolate cysts, thickness of endometrium, and serum CA125 concentration) and safety.

Results: After oral administration of SR-16234 40 mg for 12 weeks, there were statistically significant decreases in pelvic pain VAS, total pelvic pain score, total dysmenorrhea score, stiffness of Douglas' pouch, limitation of uterine movement compared with the baseline values.

Conclusion: The present trial suggested that a selective estrogen receptor modulator could be used for treatment of pain associated with endometriosis for the first time.

Keywords: endometriosis; estrogen receptor; open clinical trial; pelvic pain; selective estrogen receptor modulator.

Fig. 1.

Effects of SR-16234 on pelvic pain VAS in endometriosis patients. Differences in the changes of VAS were analyzed with the paired t-test. Data are represented as mean ± standard deviation. (n = 10, ** P < 0.01, ***P < 0.001) VAS, visual analogue scale.

Fig. 2.

Effects of SR-16234 on total pelvic pain score in endometriosis patients. Differences in the changes of score were analyzed with the paired t-test. Data are represented as mean ± standard deviation. (n = 10, ** P < 0.01, *** P < 0.001)

Fig. 3.

Effects of SR-16234 on total dysmenorrhea score in endometriosis patients. Differences in the changes of score were analyzed with the paired t-test. Data are represented as mean ± standard deviation. (n = 10, *** P < 0.001)

Fig. 4.

Effects of SR-16234 and dienogest on pelvic pain score (VAS) in endometriosis patients. Data of dienogest and placebo were derived from common technical document (CTD).