Efficacy and Safety of TBS-2 Testosterone Gel in Women With Acquired Female Orgasmic Disorder
Condition: Female Orgasmic Disorder
MeSH terms: Sexual Dysfunctions, Psychological
Intervention: Placebo; Low dose TBS-2; Medium dose TBS-2; High dose TBS-2
Intervention description: placebo intranasal gel administered prn, 2-8 hours before a planned sexual event; Low dose testosterone intranasal gel administered prn 2-8 hrs before a planned sexual event; Medium dose testosterone intranasal gel administered prn 2-8 hrs before a planned sexual event; High dose testosterone intranasal gel administered prn 2-8 hrs before a planned sexual event
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 253.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Testosterone

Summary:

      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.
    

Eligibility criteria:

        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.