Efficacy and safety of ospemifene in postmenopausal women with moderate-to-severe vaginal dryness: a phase 3, randomized, double-blind, placebo-controlled, multicenter trial

Abstract

Objective: To evaluate the safety and efficacy of ospemifene for the treatment of moderate to severe vaginal dryness in postmenopausal women with vulvovaginal atrophy (VVA).

Methods: This 12-week, multicenter, double-blind phase 3 study randomized postmenopausal women (aged 40-80 years) with VVA and moderate to severe vaginal dryness as their most bothersome symptom to daily oral ospemifene 60 mg or placebo. Coprimary efficacy endpoints included changes from baseline to week 12 in percentages of vaginal parabasal and superficial cells, vaginal pH, and vaginal dryness severity with ospemifene versus placebo; other secondary endpoints were evaluated (weeks 4, 8, and 12). Safety was assessed by treatment-emergent adverse events (TEAEs) and endometrial biopsies.

Results: Women (n = 631; ospemifene [n = 316], placebo [n = 315]) had a mean age of 59.8 years, a mean body mass index of 27.2 kg/m, and most were white. Ospemifene significantly improved (P < 0.0001) the percentages of parabasal and superficial cells, vaginal pH, and severity of vaginal dryness severity compared with placebo at week 12; significant between-group differences were noted by week 4. Secondary endpoints of dyspareunia (P < 0.001), maturation value (P < 0.0001), and the Female Sexual Function Index (P < 0.05) also significantly improved with ospemifene versus placebo at week 12. Significantly more women responded (31.5% vs 6.0%; P < 0.0001) or were satisfied (49.2% vs 33.8%; P = 0.0007) with ospemifene versus placebo at week 12. No unexpected TEAEs, treatment-related serious TEAEs, thrombotic events, or endometrial hyperplasia or carcinoma were observed.

Conclusions: Ospemifene was effective and well tolerated for the treatment of moderate-to-severe vaginal dryness in postmenopausal women with VVA.

Trial registration: ClinicalTrials.gov NCT02638337.

FIG. 1

Participant disposition. ITT, intent-to-treat; mITT, modified intent-to-treat; PP, per protocol.

FIG. 2

LS mean changes (±SE) from baseline in (A) parabasal cells, (B) superficial cells, and (C) vaginal pH at weeks 4, 8, and 12 in the ITT population. ^∗P < 0.0001 versus placebo. ITT, intent-to-treat; LS, least squares; SE, standard error.

FIG. 3

Changes in points for severity scores of vaginal dryness as the MBS at weeks 4, 8, and 12 in the ITT population (GEE model). GEE, generalized estimating equations; ITT, intent-to-treat; MBS, most bothersome symptom.

FIG. 4

Proportion of responders with ospemifene and placebo at weeks 4, 8, and 12 (ITT population). ^∗P < 0.0001 versus placebo. A responder was a woman who experienced improvements from baseline of 10 points or more in the maturation value, 0.5 points or more in vaginal pH, and 1 point or more in the MBS of vaginal dryness severity. ITT, intent-to-treat; MBS, most bothersome symptom.

FIG. 5

Change from baseline in Female Sexual Function Index total score with ospemifene and placebo at weeks 4, 8, and 12. ^∗P = 0.0392 versus placebo.

FIG. 6

Overall satisfaction with ospemifene and placebo at week 12 (ITT population). ^∗P = 0.0007 versus placebo for overall distribution using Wilcoxon rank-sum test. ITT, intent-to-treat.