(123) Preliminary Efficacy of Sildenafil Cream, 3.6% in an Exploratory, Randomized, Placebo-Controlled, Phase 2b Trial for the Treatment of Female Sexual Arousal Disorder

Abstract

Abstract Introduction Female sexual arousal disorder (FSAD) is a persistent or recurrent inability to attain, or to maintain until completion of the sexual activity, an adequate lubrication-swelling response of sexual excitement that causes marked distress or interpersonal difficulty. The biologic mechanisms leading to FSAD are similar to male erectile dysfunction. Objective To test the preliminary efficacy of topical Sildenafil Cream, 3.6% among women with FSAD in a randomized, placebo-controlled, double-blind, exploratory Phase 2b study. To describe, using validated 28-day recall instruments, changes in sexual function with treatment, and to validate exploratory sexual function questionnaires in a placebo-controlled trial. Methods Healthy pre-menopausal women, aged 18-years or older and their sexual partners, if applicable, were screened and provided written informed consent. An individual clinical interview with each volunteer was conducted in order to establish that FSAD was present and was the primary sexual dysfunction concern. Women at risk of pregnancy used effective contraception during the study. Women or their partners were excluded if they had un-controlled hypertension, a history of serious cardiac events (e.g. myocardial infarction, stroke), orthostatic hypotension or other serious medical co-morbidities. The co-primary efficacy endpoints were measured by the arousal sensation domain of the sexual function questionnaire (SFQ28) and question 14 of the female sexual distress scale (FSDS). After a one-month, no drug, run-in period, and a one-month, single-blind placebo, run-in period, 200 eligible women were randomized to receive Sildenafil Cream, 3.6% (n=101) versus placebo cream (n=99). Participants applied 2 grams of the investigational product to the clitoris, vestibule, labia minora and anterior distal vagina 10 – 20 minutes prior to each partnered or un-partnered sexual experience. During the 12-week, double-blind treatment period, participants were seen monthly and completed validated, 28-day recall questionnaires. Efficacy was also measured by a 12-question Arousal Diary (AD), completed within 24 hours of each sexual experience. Results Volunteers (n=833) underwent informed consent in this ethics board (Advarra Pro 00049161) and U.S. Food and Drug Administration approved study (IND 119922), registered at ClinicalTrials.gov (#NCT04948151). There were 1131 Sildenafil and 951 placebo exposed sexual experiences recorded in the AD during the double-blind treatment period. Sildenafil Cream, 3.6% treated women had a higher proportion of satisfactory sexual events than placebo users. At 12-weeks of use, there was improvement in the co-primary endpoint of arousal sensation consistent with how women reported meaningful improvement in an exit interview at the end of the study, although this did not achieve statistical significance. Sildenafil Cream, 3.6% treated women showed improvements in pre-specified exploratory endpoints that evaluated various aspects of the sexual experience including desire (p=0.02), arousal lubrication (p = 0.059) and orgasm (p=0.066) after 8 weeks of product use. Conclusions Data from this exploratory, placebo-controlled study of topical Sildenafil Cream, 3.6% for the treatment of FSAD in healthy premenopausal women support further clinical development of this first potential treatment for FSAD. Disclosure Yes, this is sponsored by industry/sponsor: Dare Bioscience and Strategic Sciences and Technologies (SST), LLC. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Dare Bioscience and SST LLC.