Efficacy and Safety of TBS-2 Testosterone Gel in Women With Acquired Female Orgasmic Disorder

Study Overview
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Brief Summary
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The purpose of this study is to assess and compare the effects of 3 dose strengths of TBS-2 intranasal testosterone gel to placebo on the occurrence of orgasm.

Official Title
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A Placebo-Controlled, Randomized, Double-Blind, Parallel-Group, Dose-Finding Trial to Evaluate the Efficacy and Safety of TBS-2 Intranasal Testosterone Gel in Women With Acquired Female Orgasmic Disorder

Conditions
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Female Orgasmic Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: Low dose TBS-2
* Drug: Medium dose TBS-2
* Drug: High dose TBS-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subjects who meet the following criteria may be included in the study: At Visit 1:≤ Be a generally healthy female aged 18 years and older, inclusive, who has no physical impediment to sexual function Have a diagnosis of acquired female orgasmic disorder defined as absence of orgasm during the past 6 months and according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria. Subtype should be generalized and not due to etiological factors that would be unlikely to be related to hormone function (eg, depression, relationship discord, alcoholism, surgery, injury). Hypoactive sexual desire disorder as a co-morbid disorder is allowed only if it began after the female orgasmic disorder diagnosis; Have a score of >15 with a score of ≥2 for question #15 on the FSDS DAO at Screening Visit; Be a sexually active, hetero- or homosexual woman in a steady relationship for at least 6 months and agree to have at least 4 sexual events over 28-day period of time. The subject's partner should not have any untreated sexual dysfunctions; Be on a reliable birth control method (ie, stable systemic hormonal contraception for the whole duration of the study and 30 days after study completion [for at least 3 months prior to study], IUD, barrier method) or not engaging in heterosexual intercourse. Birth control method used by subject at screening is not to be changed during the course of the study; Have a normal ENT examination; Have a body mass index ≤35; Have a clinically acceptable pelvic examination and Pap smear as read by a licensed laboratory facility (no evidence of malignancy) within the 2 years prior to Randomization; Have a clinically acceptable mammogram; Be able to complete a web-based questionnaire within 24 hours of each sexual event; Be able to read English and provide written informed consent; and At Visit 2: Have at least 4 sexual events and an absence of orgasm during the 28 day Screening/Baseline Period as determined by MONASH WHP FSSQ. Exclusion Criteria Subjects who meet any of the following criteria will not be eligible to participate in the study: Have a known history of hypersensitivity to testosterone or any component of the study drug; Have a history of any clinically relevant psychiatric disorder that could impact sexual functioning, contribute to increased risk for patient safety, or significantly compromise participation in the study (eg, bipolar disorders, psychotic disorders, severe anxiety, eating disorders, borderline personality disorder, untreated Major Depressive Disorder); Have a score of ≥14 on the Beck Depression Inventory II at Screening Visit. Subjects with a score of ≥14 and ≤19 at Screening may be eligible to participate in the study if a specialist (psychologist or psychiatrist) concludes that the subject is not clinically depressed; Have other concurrent female sexual dysfunction disorders as defined by DSM-IV criteria, eg, Sexual Aversion Disorder, Substance-Induced sexual dysfunction, dyspareunia (not caused by inadequate foreplay stimulation or alleviated by lubricants), vaginismus, Gender Identity Disorder, paraphilia, or sexual dysfunction due to a general medical condition; Be experiencing relational discord; Have a history of dementia or other neurodegenerative diseases, organic brain disease, stroke, transient ischemic attacks, brain surgery, significant brain trauma, multiple sclerosis, spinal cord injury, peripheral neuropathy, and epilepsy (febrile seizures limited to childhood do not exclude patients); Be currently receiving treatment with selective norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) and/or medications that interfere with the metabolism of testosterone (eg, anastrozole, clomiphene, testolactone, ketoconazole, spironolactone, histamine 2 [H2 receptor blockers, etc.]); Have a history of, or current evidence of, abuse of alcohol or any drug substance, licit or illicit, or be a regular drinker of more than 3 units of alcohol daily (1 unit = 300 mL beer, 1 glass wine, 1 measure spirit); Have a history of cancer other than nonmelanotic skin cancer; Have a history of deep venous thrombosis or coagulation disorders; Have a significant medical condition (eg, hepatic, renal cardiovascular, endocrine including diabetes mellitus). Subjects with treated hypertension, treated hyperlipidemia, or treated thyroid disease will not be excluded provided they have been on stable therapy for at least 3 months; Had any major surgical procedure within the past 6 months including hysterectomy, hysterectomy with bilateral salpingo oophorectomy, or vaginal incontinence surgery Are receiving treatment with systemic glucocorticosteroids, sex steroid hormones such as androgens (eg, dehydroepiandrosterone [DHEA]) or gestagens (eg, anabolic steroids) and using any post menopausal hormone therapy; Have a history of severe or multiple drug allergies, severe adverse drug reaction or drug-related leucopenia; Have a history of nasal disorders (eg, atrophic rhinitis, polyposis, abuse of nasal decongestants, clinically relevant nasal septum deviation, recurrent epistaxis), sinus disease or nasal surgery and/or seasonal or perennial allergic rhinitis in the active phase; Be using any form of chronic intranasal medication delivery, specifically nasal corticosteroids or decongestants; Have a diagnosis of sleep apnea and be using a continuous positive airway pressure/automatic positive airway device; Have a history of diagnosed hirsutism, alopecia or clinically significant acne; Have a history of diagnosed polycystic ovarian syndrome; Have pelvic inflammatory disease, chronic urinary tract, vaginal, or cervical infections, interstitial cystitis, vulvodynia, or significant symptomatic vaginal atrophy; Are currently pregnant, by history or positive serum pregnancy test at Screening Visit or have been pregnant within the 12 months prior to Screening Visit; Is breast feeding or have breast fed within the 6 months prior to Screening Visit; Are positive for hepatitis B-surface antigen, hepatitis C, or Human Immunodeficiency Virus (HIV); Have abnormal thyroid stimulating hormone level; For pre-menopausal women, have SHBG value <18 86 nmol/L; For post-menopausal women, have SHBG value >160 nmol/L Have any medical or psychiatric condition, physical examination finding, or laboratory result which, in the opinion of the principal investigator, would put the subject at additional medical risk or make her unlikely to be able to comply with study requirements; or Have received any drug as part of a research study within 30 days prior to the Screening Visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo intranasal gel administered prn, 2-8 hours before a planned sexual event | Drug: Placebo<br>* placebo intranasal gel administered prn, 2-8 hours before a planned sexual event<br>|
| Experimental: Experimental 1<br>Low dose TBS-2 (0.6 mg) testosterone intranasal gel administered prn | Drug: Low dose TBS-2<br>* Low dose testosterone intranasal gel administered prn 2-8 hrs before a planned sexual event<br>|
| Experimental: Experimental 2<br>Medium dose TBS-2 (1.2 mg) testosterone intranasal gel administered prn | Drug: Medium dose TBS-2<br>* Medium dose testosterone intranasal gel administered prn 2-8 hrs before a planned sexual event<br>|
| Experimental: Experimental 3<br>High dose TBS-2 (1.8 mg) testosterone intranasal gel administered prn | Drug: High dose TBS-2<br>* High dose testosterone intranasal gel administered prn 2-8 hrs before a planned sexual event<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Orgasms Over an 84 Day Period Compared to Placebo Over the Entire Treatment Period |  | 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Sexual Event Satisfaction Over a 28-day Period (Day 57 to Day 84) Compared to Baseline (Day -28 to Day 0) | as measured by Monash Women's Health Program Female Sexual Satisfaction Questionnaire (MONASH WHP FSSQ) question 11. MONASH WHP FSSQ question 11 asks participants to comment on how satisfying they found the sex to be from Not at all to Very much so. The lowest score is 1 and the highest is 9. All scores for each 28-day period were averaged. Change from baseline was obtained by subtracting baseline 28-day average from the 28-day period at the end of the study (Day 57 to 84). | Baseline (Day -28 to Day 0) and End of Study (Day 57 to 84) | 
| Change in Distress Due to Female Orgasmic Disorder From Day 0 Baseline to Day 84 | as measured by Female Sexual Distress Scale (FSDS-DAO) Question #15 on Day 0 and 84, respectively. Question #15 evaluates the level of distress related to problems with orgasm. It is rated on a 5-point Likert scale (from 0 to 4, i.e. never [0], rarely [1], occasionally [2], frequently [3], or always [4]). Higher scores indicate more distress. | Day 0 and Day 84 | 
| Change in Global Sexual Functioning From Day 0 to Day 84 | as measured by Female Sexual Function Index (FSFI) on Day 0 and 84, respectively. The FSFI, a 19-item questionnaire, has been developed as a brief, multidimensional self-report instrument for assessing the key dimensions of sexual frustration in women. The questionnaire provides scores on 6 domains of sexual function (desire, arousal, lubrication, orgasm, satisfaction, and pain) as well as a total score. Fifteen items are rated on a 6-point Likert scale (from 0 to 5) and 4 items on a 5-point Likert scale (from 1 to 5). The scores are added and converted using a conversion factor so that the maximum score for each domain is 6. The overall FSFI score can range from 2 to 36. Higher scores indicate better or higher sexual function. | Day 0 and Day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Testosterone