• Safety: adverse events, physical examinations, clinical laboratory evaluations
  
• Female Sexual Function Index domain scores and totals [ Time Frame: Baseline to Visit 6 (12 weeks) ]
  

• Efficacy: incidences for remaining FSEP© questions, FSFI© (all domains), FSDS©, global assessment questions, WITS©, QCTS©, Beck Depression Inventory, Dyadic Adjustment Scale, sexual encounter frequency, drop out rates
  

This Phase 3 study is being conducted to evaluate the efficacy and safety of Zestra(TM) compared to a placebo oil in women diagnosed as having acquired mixed interest/desire/arousal/orgasm disorders with varying presentations of each component in conditions of home use in conjunction with sexual activities. The study is a randomized, placebo-controlled, double-blind, parallel design trial. After subject screening, there is an open-label, placebo run-in period of four weeks, followed by a double-blinded 12 week treatment period. This design is consistent with the Paris 2003 recommendations for female sexual dysfunction (FSD) clinical trials and the Food and Drug Administration (FDA) Guidance on Clinical Development of Products for the Treatment of Female Sexual Dysfunction although the duration of active treatment in this study is 12 weeks rather than the 6 months suggested by the FDA for Phase 3 studies.

Primary efficacy assessment will be the subjects’ assessments of “successful and satisfactory” sexual encounters as recorded in a diary (question 10 in the Female Sexual Encounter Profile [FSEP©]). Secondary evaluations of efficacy will include the other FSEP questions, a subject self-assessment questionnaire (Female Sexual Function Index [FSFI©]), two global assessment questions, a treatment satisfaction questionnaire (WITS©), the Beck Depression Inventory, the Dyadic Adjustment Scale (DAS), a consumer testing survey (QualiLife Consumer Testing Survey [QCTS©]), and a distress scale (Female Sexual Distress Scale [FSDS©]), sexual encounter frequency, and drop-out rates.

The selection of outcome measures in this study is based on the most current information available. The FSEP© has been used in many FSD studies and specifically meets the FDA recommendations for a primary outcome measure. The initial validation study of the FSEP© was presented at the 11th World Congress of the International Society for Sexual and Impotence Research in Buenos Aires in 2004. The FSFI©, the FSDS©, and global assessment questions are routinely used in FSD trials, and the first two have been subjects of ongoing validation for a number of years.

Global assessment questions have historically been used to calculate response rates. The QCTS© is a consumer testing survey which addresses issues ultimately impinging on product marketability. WITS© is a female oriented treatment satisfaction instrument newly developed by Stanley E. Althof, Ph.D., Eric W. Corty, Ph.D., and Miki Wieder, M.A., 2004; the authors’ authorized use of this instrument in this study is part of the ongoing validation for this questionnaire. Since depression can contribute to FSD and FSD can contribute to depression, seriously confounding diagnostic and treatment schema, the commonly used Beck Depression Inventory will be administered at the end of the baseline run-in period and then at the end of the double-blinded treatment period.

Relational factors have the same confounding issues as depression; thus, the participants’ attitudes about their relationships with their partners will be assessed at baseline and end of treatment using the Dyadic Adjustment Scale. Sexual encounter frequency may prove a useful outcome measure since a beneficial effect of treatment may be reinforcing, while lack of efficacy by the placebo may be discouraging. A similar hypothesis is the basis of drop-out analysis.