Using Thermography to Assess the Affects of Sildenafil Cream, 3.6%

Inclusion Criteria:

• Subject must be a premenopausal woman at least 18 years of age.
• Subject must be willing to avoid high protein meals and follow dietary guidanceprovided by the study site staff for the duration of the study.
• Women of childbearing potential must be using an acceptable form of birth control (i.e., intrauterine system [IUS], progestin and/or estrogen-containing hormonalcontraceptives, contraceptive patch, contraceptive implant, contraceptive ring, orcontraceptive injection) or the copper-containing intrauterine device (IUD) and mustbe on a stable dose or have had the insert/implant for at least 1 month withoutcomplication prior to Visit 1 and agree to continue to stay on their birth control forthe duration of the study. Condoms (latex or polyisoprene only) are not considered anacceptable form of birth control but may be used to prevent exposure to sexuallytransmitted infections. An attempt will be made to enroll at least 30% of women whoare using hormonal contraception and at least 30% who are not.
• Subject reports she has viewed heterosexual pornography prior to Visit 1 and issexually aroused from watching heterosexual porn or sexually explicit videos depictingmen and women engaging in sexual activity.
• Subject has a body mass index (BMI) < 38 kg/m². Subjects with a BMI >30 kg/m2will bevisually evaluated to ensure that there will not be physical interference with viewingthe areas of interest by the thermography camera. If the investigator deems thatinterference is likely due to BMI, the subject will be excluded.
• Subject has a normal electrocardiogram at Visit 1.
• Subject is capable of understanding and complying with the protocol and agrees to signthe informed consent document.
• Subject has been sexually active (in the past 4 weeks since Visit 1). Sexual activitycan include caressing, foreplay, masturbation, and vaginal intercourse.
• Subject is fluent in the English language.
• Subject is willing to trim pubic hair (if necessary) to allow for accurate genitaltemperature readings and visualization of the genital regions of interest.
• Subject has had a Pap smear performed within three years prior to Visit 1 and canprovide documentation indicating results that are either normal or atypical squamouscells of undetermined significance (ASCUS) but negative for Human Papilloma Virus (HPV) (based on current guidelines as published by the U.S. Prevention Services TaskForce). If the subject cannot provide documentation, a Pap smear will be performed atVisit 1. Subjects with abnormal findings will be excluded from study participation andbe referred for follow-up medical care as appropriate.
• Subject is in good health for age, as determined by physical and gynecological historyand examination at Visit 1.
• Subject agrees to withhold from smoking tobacco products 24 hours prior to all visits.
• Subject agrees to use compatible condoms (latex or polyisoprene) if she chooses toengage in vaginal or anal intercourse with her partner and abstain from receptive oralsex throughout the Double-Blind Dosing Phase and for seven days following thecompletion of Visit 4 to avoid potential partner exposure to the IP and to helpprevent the transmission of sexually transmitted infections. Condoms should be usedconcurrently with subject's acceptable contraceptive method.
• Subjects must agree to not use vaginal or vulvar lubricants, spermicides, creams orgels, contraceptive foams, or vaginal douche products from Visit 1 until after thefollow-up safety call is completed 7±3 days after Visit 4.

Exclusion Criteria:

• Subject is nursing or pregnant (based on positive urine pregnancy test) or wishes tobecome pregnant during the study period.
• Subject has any disorder or a history of any disorder that may prevent the successfulcompletion of the study in the opinion of the Investigator.
• Subject has used any topical hormone replacement therapy (HRT) applied locally to thegenitals in within three months of Visit 1.
• Subject has a significant cardiovascular, hepatic, metabolic, renal, respiratory,gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic,genitourinary, or psychiatric disease or other unstable medical condition that wouldcontraindicate administration of study medication, interfere with study evaluation,limit study participation, or confound the interpretation of study results in theopinion of the Investigator.
• Subjects with controlled, treated thyroid disease on a stable medication for the past 6 months will be considered eligible. Thyroid Stimulating Hormone (TSH) must be withinnormal range (confirmed by laboratory test).
• Subjects with controlled, treated hypertension on a stable dose of ACE Inhibitors orAngiotensin II Receptor Blockers for the past 6 months will be considered eligible.
• Subject had an active ulcer or clinically significant bleeding disorder.
• Subject is actively menstruating at Visit 1 or has reported abnormal spotting in the 3months preceding Visit 1.
• Subject has a history of myocardial infarction, stroke, or life-threatening arrhythmiawithin 6 months prior to Visit 1; or any history of coronary disease-causing angina;or congestive heart failure requiring medical intervention.
• Subject has retinitis pigmentosa or sickle cell anemia or related anemias, even if thesubject feels clinically well at the time of Visit 1. Subjects with retinitispigmentosa will be identified by specifically asking whether they have the condition,if there are visual signs and symptoms of the condition (including questioningsubjects as to whether they have difficulty seeing at night or in low light, and ifthey have any visual field deficits that indicate a loss of peripheral or centralvision), or if there is a family history.
• Subject has a history of orthostatic hypotension or orthostatic hypotension which ispresent at Visit 1, defined as a drop in systolic blood pressure ≥ 20 mm Hg, a drop indiastolic blood pressure ≥ 10 mm Hg or experiencing lightheadedness or dizziness at 1or 3 minutes after the change in position from supine to standing.
• Subject reports a history of sexual dysfunction (e.g., anorgasmia, vaginismus,hypoactive sexual desire disorder, arousal difficulties etc.).
• Patient has dyspareunia, vulvovaginal infection or inflammation, inflammatorydisorders of the vulva or vagina, vestibulodynia, clitorodynia, Genitourinary Syndromeof Menopause (GSM) or vulvovaginal atrophy.
• Subject has insulin dependent type 1 or type 2 diabetes.
• Subjects who do not demonstrate a greater positive slope for genital temperaturechange over time during the Sexually Explicit Video Session as compared to the NeutralVideo Session during the 'no-cream' familiarization session at Visit 1 will not beeligible to advance into the Double-Blind Dosing Phase of the study. Any positiveslope (i.e., any genital temperature increase, slope>0) during the sexually explicitfile viewed in Visit 1 is considered qualifying for subjects to proceed into thedouble-blind dosing phase.
• Patient has undergone major pelvic surgery or abdominal surgery that may have causednerve damage, including, vulvectomy and vestibulectomy.; neurological impairment dueto diabetes, stroke, pelvic nerve damage secondary to trauma, cancer treatments,myasthenia gravis, multiple sclerosis or spinal cord damage.
• With the exception of anxiety and depression, patient has any current and/orpreviously reported diagnoses of DSM-IV-TR axis I disorders (e.g., schizophrenia,bipolar disorder) including delirium, dementia and amnestic disorders.
• Patients diagnosed with anxiety or depression must be controlled, as determined by theInvestigator, and if on a medication (i.e., SSRIs, SNRIs, buspirone, bupropion andbenzodiazepines), on a stable dose for at least the past 6 months.
• Patients who have any history of antipsychotic therapy within the last year will beexcluded unless given for diagnosis of anxiety and/or depression and on a stable dosefor the past 6 months if taking currently.
• Subject has a history of cancer, other than basal cell carcinoma.
• Subject has any surgical or medical condition that may interfere with the absorption,distribution, metabolism, or excretion of the test article in the opinion of theInvestigator.
• Subject has a history of drug abuse within 1 year prior to Visit 1.
• Subject has a history of alcoholism within 1 year prior to Visit 1, admitted alcoholabuse, average consumption of more than 1 standard unit of alcohol per day (a standardunit equals 12 ounces of beer, 1½ ounces of 80-proof alcohol, or 6 ounces of wine).
• Subject has a history of non-arteritic ischemic optic neuropathy (NAION).
• Subject has had treatment currently or within 1 month (28 days) prior to Visit 1 withany of the following:

1. Dehydroepiandrosterone (DHEA), excluding intravaginal DHEA, testosterone andother androgens, tamoxifen, raloxifene, and other selective estrogen receptormodulators (SERMs)
2. Any antihypertensive (excluding ACE Inhibitors or Angiotensin II ReceptorBlockers), clonidine, alpha blockers or nitrate containing medications.
3. Beta blockers or other drugs that affect the autonomic nervous system and/orcardiovascular system
4. Any approved or experimental medications or treatments used to enhance the sexualresponse (e.g., oral sildenafil, L-arginine)
5. Any drugs or supplements that may alter amino acid or vitamin status, such asdrugs or supplements containing L-arginine or Citrulline.

• Subjects who are currently being treated daily with weak, moderate, and stronginhibitors and inducers of CYP3A4 and CYP2C9 enzymes (e.g., CYP3A4: ketoconazole,clarithromycin, verapamil, diltiazem, St. John's Wort / CYP2C9: fluconazole,oxandrolone, fluvastatin, and metronidazole), Seville oranges, or any prescription,over-the-counter (OTC) medications, or herbal products known to inhibit or induce the 2 enzymes listed above must agree to continue taking the supplement or medication atapproximately the same time each day for the duration of the study period, assumingthe Investigator or subject's provider deems appropriate. If the subject is using thesupplement or medication PRN, that subject must wash out (i.e., 6 half-lives) for theduration of the study period (Visit 1 to Visit 3), assuming the Investigator orsubject's provider deems appropriate. If the subject takes any prescription or OTCdrugs at the direction of a health care provider that are inhibitors or inducers ofCYP3A4 and CYP2C9, that provider should be consulted before medications are stoppedfor the purposes of study participation.
• Subject has positive findings from the urine drug screen (e.g., amphetamines,barbiturates, benzodiazepines, cocaine, methadone, and opiates).
• Subject has positive findings for sexually transmitted infection (gonorrhea,chlamydia, trichomoniasis), or human immunodeficiency virus (HIV) antibodies.
• Subject reports having an outbreak (blisters, warts or vesicles) due to any of thefollowing sexually transmitted diseases: genital herpes or HPV at any time point inthe past three months.
• Subject has participated in any clinical research study evaluating anotherinvestigational drug or therapy within 30 days before Visit 1 (or 6 half-lives of theinvestigational agent, whichever is longer).
• Subject has any abnormal findings on vulvar-vaginal examination performed during thephysical and gynecological exams at Visit 1 (e.g., genital skin breaks, irritation,dermatoses, or lesions).
• Subject has a genital piercing(s) or plans to get a genital piercing(s) during thestudy period which could interfere with thermal camera data collection or studyobjectives, as determined by the Investigator.
• Subject has moderate to severe current vaginitis, a vaginal infection includingbacterial vaginosis (BV) or a yeast infection. The diagnosis of yeast infectionsshould be made by the Investigator based on the physical and gynecological exams; theobjective is to exclude women that are symptomatic. If the woman is not complaining ofsymptoms but the Investigator observes discharge, then a vaginal wet mount test shouldalso be performed to confirm a diagnosis of yeast and Amsel criterion for confirmationof BV infection.
• Subject has a pelvic or urinary tract infection.
• Subject self-reports a known hypersensitivity to any ingredients in theInvestigational Product (IP).
• Subject reports an orthopedic condition (e.g., labral tear, hip osteoarthritis) thatmay interfere with study participation, in the opinion of the Investigator, withregard to the thermography procedure during Visits 1 through 4.