O-209: A randomized, multicenter, double-blind, placebo-controlled trial to evaluate the efficacy and safety of synthetic conjugated estrogens, B (SCE-B [Enjuvia ™]) 0.3 mg tablets for the treatment of vulvovaginal atrophy in healthy postmenopausal women

Abstract

The primary objective of this study was to evaluate the safety and efficacy of oral daily SCE-B 0.3 mg tablets for the treatment of vulvovaginal atrophy in symptomatic postmenopausal women. This was a prospective, randomized, multicenter, double-blind, placebo-controlled trial. 310 postmenopausal women aged 30 through 80 years (mean age 58.6 y) who had at least one symptom of vaginal atrophy rated as moderate or severe, were randomized to a daily dose of either SCE-B 0.3mg (n=154) or matching placebo (n=156) for 12 weeks. Mean changes in vaginal maturation index (VMI), vaginal pH, and severity of the ”most bothersome symptom“ ([MBS]-defined by the patient at baseline as the moderate or severe self-assessed symptom considered most bothersome) were determined from baseline to the end of treatment. Six symptoms were considered for determination of the MBS: vaginal dryness, vaginal irritation/itching, vaginal soreness, difficulty passing urine, pain during intercourse, and bleeding after intercourse. For the VMI, additional evaluation was performed on the mean changes in the percentage of parabasal and superficial cells. Mean change in the three endpoints (VMI, pH, and MBS) between baseline and Days 14, 21, 28, 56, and 84 was also assessed. Safety and tolerability were evaluated by comparison between treatment groups of adverse events, clinical findings, and laboratory results. Patients who received at least one dose of study medication, met the study protocol requirements at baseline for all three efficacy inclusion criteria (VMI, pH, and MBS), and had at least one post-randomization assessment of vaginal atrophy consisting of all three endpoints, served as the primary cohort for inferences regarding efficacy (SCE-B, n=125; placebo, n=123). The SCE-B group exhibited significantly greater differences in VMI (p<.0001) and vaginal pH (p<.0001) from baseline to the end of treatment, compared with placebo. Consistent with the changes in the VMI, a significant increase was seen in the percentage of superficial cells (p<.0001) with a corresponding significant decrease in the percentage of parabasal cells (p<.0001) for the SCE-B group compared with placebo. The breakdown of symptoms chosen as most bothersome at baseline was comparable across treatment groups, with most patients selecting vaginal dryness (44.4%) or pain during intercourse (30.2%) as most bothersome. There was a statistically significant mean reduction in the severity of the MBS for the SCE-B group compared with placebo (p<0.0001); this mean reduction in MBS severity was more than twice that observed for placebo. The incidence of adverse events was comparable for both groups and there were no clinically significant differences observed between the groups in laboratory parameters or other clinical findings related to safety. No serious adverse events were reported in the SCE-B group. SCE-B, at a dose of 0.3mg/day was shown to be effective in treating vulvovaginal atrophy in symptomatic postmenopausal women compared with placebo. A significant increase in the VMI and significant decrease in vaginal pH were observed in the SCE-B group following up to 12 weeks of treatment. A significant reduction in the severity of the MBS was also observed from baseline to the end of treatment for those women treated with SCE-B.