A Phase 2, Randomized, Double-blind, Placebo-controlled Proof-of-Concept Study to Evaluate the Efficacy and Safety of Estetrol in Postmenopausal Subjects With Female Sexual Arousal Disorder
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Estetra
- 入组人数
- 82
- 试验地点
- 25
- 主要终点
- Change from Baseline to Week 12 in feeling concerned by difficulties with sexual arousal, assessed by FSDS-DAO Item 14.
研究概览
简要总结
This randomized, double-blind, placebo-controlled clinical trial investigated the effect of once daily oral administration of 20 mg estetrol monohydrate tablet for 12 weeks in postmenopausal women who experienced sexual arousal disorder. Specifically, the main aim was to evaluate whether estetrol (E4) is effective in the treatment of female sexual arousal disorder (FSAD) in women after their menopause.
详细描述
Female Sexual Arousal Disorder (FSAD), a subtype of female sexual dysfunction, is an inability to attain or to maintain an adequate lubrication-swelling response of sexual excitement. FSAD may manifest as a decrease in vaginal lubrication and a decrease in genital sensation related to blood flow and can cause marked distress and/or interpersonal difficulty (Diagnostic and Statistical Manual (DSM) of Mental Disorders, 4th edition [DSMIV]). Estrogen has a role in maintaining genital tissue structural integrity and pelvic nerve-stimulated genital blood flow.
This study was conducted with estetrol (E4), assessing the efficacy and safety of estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, for the treatment of FSAD associated with menopause in hysterectomized postmenopausal women.
The design of this Phase 2, Proof of Concept (POC) study was: randomized, double-blind, placebo-controlled, two-arm parallel group. Eligible subjects were randomized in a 1:1 ratio and received either an oral tablet of E4 20 mg or placebo, once daily for 12 weeks. Placebo tablet looked identical to E4 but had no active ingredient. During the study, participants visited the clinic 7 times and completed a daily e-diary. The results were evaluated regarding the effect of E4 and placebo on the sexual arousal of the participants, using several validated questionnaires.
The primary efficacy endpoints were the change from Baseline to Week 12:
- in feeling concerned by difficulties with sexual arousal, assessed by Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) Item 14;
- in the Sexual Function Questionnaire (SFQ-28) Arousal-Sensation Domain (Questions 6 to 9).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Main Inclusion Criteria:
- •Hysterectomized postmenopausal women, ≥40 up to ≤65 years, diagnosed with Female Sexual Arousal Disorder
排除标准
- •Not willing to stop any hormonal products during their participation in the study
- •History of unresolved sexual trauma or abuse that is contributing to any sexual dysfunction problem
- •Have experienced a recent major life stress or relationship discord that could interfere with sexual activity
- •Clinically significant abnormal gynecological findings
- •History of malignancy, with the exception of basal cell or squamous cell carcinoma of the skin
- •Systolic BP higher than 140 mmHg, diastolic BP higher than 90 mmHg
- •Is judged by the investigator to be unsuitable for any reason
研究组 & 干预措施
Placebo
Matching Placebo, administered orally once daily for up to 12 weeks
干预措施: Placebo (Other)
结局指标
主要结局
Change from Baseline to Week 12 in feeling concerned by difficulties with sexual arousal, assessed by FSDS-DAO Item 14.
时间窗: 12 weeks
FSAD = Female Sexual Arousal Disorder
Change from Baseline to Week 12 in the Sexual Function Questionnaire 28 (SFQ-28) Arousal-Sensation Domain (Questions 6 to 9).
时间窗: 12 weeks
FSDS-DAO = Female Sexual Distress Scale-Desire/Arousal/Orgasm
Change From Baseline to Week 12 in Feeling Concerned by Difficulties With Sexual Arousal, Assessed by Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO), Item 14
时间窗: Baseline, Week 12.
The Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) is a validated 15-item self-assessment where each item is scored from 0 (never) to 4 (always). Higher scores on this scale, which has a total range of 0-60, indicate greater distress. Item 14 assesses how often the subject has felt concerned by difficulties with sexual arousal during the past 30 days.
Change From Baseline to Week 12 in the Sexual Function Questionnaire 28 (SFQ-28) Arousal-Sensation Domain (Questions 6 to 9)
时间窗: Baseline, Week 12.
The 28-item Sexual Function Questionnaire (SFQ-28) is a validated self-assessment tool to assess female sexual function. It has 8 domains, including domains for desire, arousal (sensation/lubrication/cognitive), orgasm, pain, enjoyment, and partner relationship. Questions are scored on a Likert scale (e.g., 0 to 5 or 1 to 5), where lower scores indicate higher levels of dysfunction. Questions 6, 7, 8, and 9 deal with the domain "Arousal-sensation". Score range for this domain is: 4-20 (=sum of Questions 6-9). Total score range is: 24-141 (=sum of all Questions 1-28).
次要结局
- Change from Baseline to Week 12 in sexual function assessed by SFQ-28 - total score.(12 weeks)
- Change from Baseline to Week 12 in severity of sexual arousal disorder as assessed by Patient Global Impression of Severity (PGIS).(12 weeks)
- Change from Baseline to Week 12 in sexual function assessed by Percentage of Satisfying Sexual Events (SSE) - captured in arousal electronic diary (ediary).(12 weeks)
- Change from Baseline to Week 12 in arousal and lubrication assessed by Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction (SexFS) measures (PROMISSexFS Questionnaire).(12 weeks)
- Change from Baseline to Week 12 in sexual function assessed by FSDS-DAO - total score.(12 weeks)
- Change from Baseline to Week 12 in sexual function assessed by PROMIS-SexFS.(12 weeks)
- Patient Global Impression of Change (PGIC) at Week 12.(12 weeks)
- Change From Baseline to Week 12 in Arousal and Lubrication Assessed by Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction (SexFS) Measures (PROMIS-SexFS Questionnaire)(Baseline, Week 12.)
- Change From Baseline to Week 12 in Sexual Function Assessed by FSDS-DAO -- Total Score(Baseline, Week 12.)
- Change From Baseline to Week 12 in Sexual Function Assessed by Percentage of Satisfying Sexual Events (SSE) -- Captured in Arousal Electronic Diary (Ediary)(Baseline, Week 12.)
- Change From Baseline to Week 12 in Sexual Function Assessed by the Sexual Function Questionnaire 28 (SFQ-28) -- Total Score(Baseline, Week 12.)
- Change From Baseline to Week 12 in Sexual Function Assessed by PROMIS-SexFS(Baseline, Week 12.)
- Patient Global Impression of Change (PGIC) at Week 12(Week 12.)
- Change From Baseline to Week 12 in Severity of Sexual Arousal Disorder as Assessed by Patient Global Impression of Severity (PGIS)(Baseline, Week 12.)