The objective of this study is to evaluate the clinical efficacy and safety of Zestra(TM) in women with acquired mixed desire/interest/arousal/orgasm disorders under conditions of home usage. The primary efficacy hypothesis will compare the effect of Zestra versus placebo on the incidence of "successful and satisfactory" sexual encounters.

Condition	Intervention	Phase
Hypoactive Sexual Desire Disorder Sexual Arousal Disorder Orgasmic Disorder	Drug: Non-prescription Zestra (TM): patented formulation	Phase III

Further Study Details: 

Primary Outcomes: Safety: adverse events, physical examinations, clinical laboratory evaluations; Efficacy: incidence of "successful and satisfactory" sexual encounters as measured from the FSEP©
Secondary Outcomes: 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
Expected Total Enrollment:  200

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.

Ages Eligible for Study:  21 Years   -   65 Years,  Genders Eligible for Study:  Female

Criteria

Inclusion Criteria:

• Female 21 to 65 years of age.
• Have been previously “functional” or experienced sexual desire/arousal/orgasm for several years in the past.
• Postmenopausal (no menses for one year and appropriate elevation of FSH), or using hormonal contraception for at least 3 months prior to study entry, or have had a tubal ligation at least 3 months prior to study entry or confining all sexual intercourse to a vasectomized partner.
• Provide written informed consent.
• Have a stable heterosexual relationship with a male partner for at least 1 year. Partner must attend screening visit and also sign a separate informed consent form.
• Have a partner score of "not impotent" or "minimally impotent" on the Single Question Assessment of Erectile Dysfunction. The subject will determine the partner score privately.
• Willing to engage in sexual activities with intent to attain orgasm at least 2 times per week.
• Meet the diagnostic criteria for one or more of the following acquired disorders: *Women’s sexual interest/desire disorder; *Subjective sexual arousal disorder; *Combined genital and subjective arousal disorder; *Genital sexual arousal disorder; *Women’s orgasmic disorder.
• Have a score of > 15 on the FSDS .
• Willing and able to understand and comply with all study requirements.

Exclusion Criteria:

• Evidence of unresolved sexual trauma or abuse.
• Primary anorgasmia, vaginismus, sexual pain disorder, sexual aversion disorder, or persistent sexual arousal disorder.
• Female sexual dysfunction caused by untreated endocrine disease, e.g., hypopituitarism, hypothyroidism, diabetes mellitus.
• Pregnant or nursing.
• Sensitivity to any of the ingredients in Zestra for Women(TM).
• Chronic or complicated urinary tract or vaginal infections within previous 12 months.
• Pelvic inflammatory disease within previous 12 months.
• Currently active sexually transmitted disease.
• Chronic dyspareunia not attributable to vaginal dryness within previous 12 months.
• Currently active moderate to severe vaginitis.
• Cervical dysplasia within previous 12 months.
• Significant cervicitis as manifested by mucopurulent discharge from the cervix.
• Significant gynecologic conditions such as uterine fibroids, vulvar vestibulitis, or vaginismus that may (in the investigator’s opinion) interfere with the subject’s ability to comply with study procedures.
• Psychoses and bipolar disorder.
• Use of neuroleptics or lithium within previous 3 months.
• Unwillingness to forego any medications, herbal treatments, or dietary supplements intended to enhance sexual function during the course of the study.
• History of myocardial infarction within previous 6 months.
• History or evidence of significant renal or hepatic disease within previous 6 months.
• Significant central nervous system diseases within the last 6 months, i.e., stroke, spinal cord injury, multiple sclerosis, etc.
• Unwillingness to omit cunnilingus from sexual activities during the study. No post-coital fellatio allowed.
• Any condition which, in the Investigator’s opinion, would interfere with the subject’s ability to provide informed consent, to comply with study instructions, or which might confound the interpretation of the study results.
• Any condition which would endanger the participant if she participated in this trial.

Please refer to this study by ClinicalTrials.gov identifier  NCT00118495

David M Ferguson, PhD, MD      218-388-0304    ferguson@boreal.org

California
      West Coast Clinical Research, Tarzana,  California,  91356,  United States
      South Orange County Medical Research Center, Laguna Hills,  California,  92637,  United States
Colorado
      Urology Research Options, Aurora,  Colorado,  80012,  United States
Florida
      South Florida Medical Research, Aventura,  Florida,  33180,  United States
Indiana
      Kinsey Institute, Bloomington,  Indiana,  47405-7686,  United States
      Northeast Indiana Research, Fort Wayne,  Indiana,  46825,  United States
Maryland
      Sexual Wellness Center, Annapolis,  Maryland,  21401,  United States
Massachusetts
      Lahey Clinic, Peabody,  Massachusetts,  01960,  United States
New Jersey
      UMDNJ-Robert Wood Johnson Medical School, New Brunswick,  New Jersey,  08901,  United States
New York
      Columbia-Presbyterian Medical Center, New York,  New York,  10032,  United States
      Accumed Research Associates, Garden City,  New York,  11530,  United States
      Hudson Valley Urology, PC, Poughkeepsie,  New York,  12601,  United States
Ohio
      MetroHealth Medical Center, Cleveland,  Ohio,  44109,  United States
Pennsylvania
      The Pelvic and Sexual Health Institute, Philadelphia,  Pennsylvania,  19146,  United States
Texas
      Urology San Antonio Research, PA, San Antonio,  Texas,  78229,  United States
Wisconsin
      Midwest Research Specialists, LLC, Milwaukee,  Wisconsin,  53209,  United States

Study chairs or principal investigators

David M Ferguson, PhD, MD, FACCP,  Study Director,  Clinical Research Services Consulting   
Julia R Heiman, PhD,  Principal Investigator,  Kinsey Institute for Research in Sex, Gender and Reproduction   

Study ID Numbers:  Z-04
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 8, 2005
ClinicalTrials.gov Identifier:  NCT00118495
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-07-26