O181 Baseline characteristics of patients enrolled in three phase III North American trials of flibanserin in premenopausal women with hypoactive sexual desire disorder

Introduction Clinical trial design in female sexual dysfunction (FSD) is an evolving science, with some areas of controversy. Aim To develop an evidence-based, expert consensus-report on design of FSD clinical research. Methods Literature review including the Food and Drug Administration (FDA) clinical trial guidelines with critique by six experts from three countries, modified after public presentation and debate. Main Outcome Measure Expert opinion and recommendations were based on grading of evidence based literature, internal committee dialogue, open presentation, and debate. Results Design of clinical research for regulatory approval is driven by FDA guidelines. Diagnostic and Statistical Manual-IV definitions and consideration of comorbidity of sexual disorders may complicate patient selection and outcomes. Measures for study end points include satisfying sexual events utilizing a daily diary, sexual distress, and patient-reported outcomes measures of the construct under study. Currently, trial duration is recommended to be 6 months for efficacy trials to allow for modification of behavioral adaptations to changes in desire. Important issues include safety assessments, generalizability, having a representative study population, stratification by reproductive status, partner assessment, contextual and interpersonal factors, symptom duration and severity, management of placebo response, and drug dosing. Statistical analysis should include assessment of change from baseline to end point between study drug and placebo, determination of statistically significant change vs. clinically meaningful effects, linear mapping of all measures of the same construct, and determination of responders and remitters. Conclusions Future trials should include clear population definitions, direct and indirect measures of the specific FSD construct, and procedures to allow generalizability of diagnosis and treatment to the target population.

Section: Additional Issues In Fsd Trialsmentioning

confidence: 96%

Section: Additional Issues In Fsd Trialsmentioning

confidence: 99%

Section: Regulatory Considerationsmentioning

confidence: 99%

Section: Safety Of Long-term Treatment and Withdrawalmentioning

confidence: 99%

See 2 more Smart Citations

Standards for Clinical Trials in Sexual Dysfunction in Women: Research Designs and Outcomes Assessment

Clayton

Dennerstein

Fisher

et al. 2010

“…T raditionally, treatment outcome research has evaluated the success of treatment in terms of efficacy, the degree to which treatment reduces symptomatology. In recent clinical trials for female sexual dysfunction (FSD) involving Flibanserin, testosterone, and an herbal supplement, the primary and secondary outcome measures were measures of efficacy-daily event logs and/or validated measures of sexual function and distress [1][2][3][4][5][6]. Daily event logs or diaries, which assess the number of satisfactory sexual experiences, are mandated by the Food and Drug Administration (FDA) as a primary end point in FSD trials [7].…”

Section: Introductionmentioning

confidence: 99%

Measuring Women’s Satisfaction with Treatment for Sexual Dysfunction: Development and Initial Validation of the Women’s Inventory of Treatment Satisfaction (WITS-9)

Corty¹,

Althof

Wieder³

2011

Aim To develop a brief, psychometrically sound, measure of satisfaction with treatment for female sexual arousal disorder. Method In Phase 1, women in focus groups generated items measuring satisfaction with treatment for arousal disorder. In Phase 2, expert clinicians/researchers and women with self-reported female sexual arousal disorder (FSAD) assessed the content validity of the items. In Phase 3, women enrolled in a double-blind treatment trial for female sexual dysfunction completed the Women’s Inventory of Treatment Satisfaction (WITS) and the Female Sexual Function Inventory (FSFI) to provide reliability and validity information. Main Outcome Measures WITS and FSFI. Results In Phase 2, 36 items demonstrated adequate content validity. In Phase 3, 20 items correlated with symptom improvement on the FSFI arousal subscale. Factor analysis sorted these items into three dimensions: initiation/receptivity satisfaction, treatment satisfaction, and perceived partner satisfaction. The three items with the highest loadings on each factor formed the WITS-9. Internal consistency (α) reliability coefficients for the total WITS-9 score and the three subscale scores were 0.92, 0.93, 0.92, and 0.79, respectively. Correlations of WITS-9 scores with the FSFI change scores for subgroups with different sexual dysfunctions offer construct validity support that the WITS-9 measures treatment satisfaction for women with a variety of sexual dysfunctions. Conclusions The WITS-9 is a brief, psychometrically sound scale that is useful for assessing treatment satisfaction in women with sexual dysfunctions. While the WITS-9 is promising, further work needs to be done to obtain reliability and validity information in additional samples.

Flibanserin: Initial Evidence of Efficacy on Sexual Dysfunction, in Patients with Major Depressive Disorder

Kennedy

2010

Introduction Flibanserin, a novel 5-HT1A agonist and 5-HT2A antagonist, has the potential to treat sexual dysfunction. Aim Provide historical perspective on the rationale for development of flibanserin to treat sexual dysfunction, based on post hoc analyses of data. Main Outcome Measures The Arizona Sexual Experiences (ASEX) scale and the Hamilton depression rating scale (HAMD) Genital Symptoms item. Methods Sexual function outcomes are presented from four double-blind, randomized controlled studies involving a total of 369 men and 523 women diagnosed with Major Depressive Disorder. Each study had an active treatment arm to confirm assay sensitivity on the primary antidepressive endpoint. Two studies placebo, flibanserin (50 mg bid), or fluoxetine (20 mg qd) for 6 weeks and two involved placebo, flibanserin (50–100 mg bid), or paroxetine (20–40 mg qd) for 8 weeks. Results Individual study completion rates were 77–80%. At baseline, 38% of men and 67% of women reported sexual dysfunction. Assay sensitivity was not demonstrated in the fluoxetine trials and sexual function outcomes were inconsistent. Flibanserin and placebo were associated with low rates of treatment-emergent sexual dysfunction in women during the paroxetine studies. In one study, 70% of flibanserin-treated women with baseline sexual dysfunction reported improvement in sexual function, compared with 30% of placebo-treated women. Mean change from baseline on the HAMD “Genital Symptoms” item in one paroxetine study was significantly better among flibanserin- than placebo-treated women at weeks 4, 6, and 8 (P <0.05). Sexual function adverse events across flibanserin groups were generally comparable to placebo. Conclusions Although these studies were not designed or powered to compare sexual function outcomes, results suggested a potential benefit of flibanserin on sexual function, particularly on female sexual desire, and provided a rationale to evaluate the efficacy of flibanserin as a treatment for female hypoactive sexual desire disorder.