A Phase 1/2, Open-label, Parallel Group Study to Evaluate the Preliminary Efficacy and Usability DARE-HRT1 (80 g Estradiol/4 mg Progesterone and 160 g Estradiol/8 mg Progesterone Intravaginal Rings) Over 12 Weeks in Healthy Postmenopausal Women

Objectives: The exploratory objectives of this study were to evaluate the usability and acceptability and to conduct a preliminary evaluation of the efficacy of DARE-HRT1. DARE-HRT1 is an intravaginal ring (IVR) that releases 17 beta 2estradiol (E-2) with progesterone (P-4) over 28 days. It is the first combination E2 and P4 IVR being developed for the treatment of vasomotor symptoms (VMS) in healthy postmenopausal women with an intact uterus. Methods: This was a randomized, open-label, 2-arm, parallel group study in 21 healthy postmenopausal women. Women were randomized (1:1) to either DARE-HRT1 IVR1 (E2 80 mu g/d with P-4 4 mg/d) or DARE-HRT1 IVR2 (E-2 160 mu g/d with P-4 8 mg/d). They used the assigned IVR for three 28-day cycles, inserting a new IVR monthly. Preliminary genitourinary syndrome of menopause (GSM) treatment efficacy was estimated by measuring changes from baseline in vaginal pH, vaginal maturation index (VMI), and changes in the severity of GSM symptoms. Preliminary systemic VMS efficacy was measured by changes in responses to the Menopause-Specific Quality of Life (MENQOL) questionnaire. Acceptability was assessed by product experience surveys. Results: Preliminary local GSM treatment efficacy was supported by significant decreases in vaginal pH and % parabasal cells, and significant increases in the overall VMI and % superficial cells for both IVR groups (all P values <0.01). PreliminaryVMS efficacywas supported by significant decreases in all domains of theMENQOL questionnaire from baseline for both dosing groups (all P values <0.01). Conclusions: Data from this study support further development of DARE-HRT1 for the treatment of menopausal symptoms.