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

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.