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

Female Orgasmic Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01607658
• Other study ID #: TBS-2-AMB-2012-01
• Status: Completed
• Phase: Phase 2
• Start date: May 2012
• Est. completion date: May 2014

Study information

• Verified date: August 2018
• Source: Acerus Pharmaceuticals Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 253
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Disease
• Female Orgasmic Disorder
• Sexual Dysfunctions, Psychological

Intervention

Drug:
• Placebo
placebo intranasal gel administered prn, 2-8 hours before a planned sexual event
• Low dose TBS-2
Low dose testosterone intranasal gel administered prn 2-8 hrs before a planned sexual event
• Medium dose TBS-2
Medium dose testosterone intranasal gel administered prn 2-8 hrs before a planned sexual event
• High dose TBS-2
High dose testosterone intranasal gel administered prn 2-8 hrs before a planned sexual event

Locations

Country	Name	City	State
Australia	Monash University	Melbourne
Australia	Keogh Institute for Medical Research	Nedlands
Australia	The Robinson Institute University of Adelaide	North Adelaide
Australia	Barbara Gross Research Unit	Randwick
Canada	Gain Medical Centre	Coquitlam	British Columbia
Canada	Alta Clinical Research Inc.	Edmonton	Alberta
Canada	Manna Research	Toronto	Ontario
Canada	Discovery Clinical Services, Ltd	Victoria	British Columbia
Canada	Victoria Clinical Research Inc	Victoria	British Columbia
Canada	Manitoba Clinic	Winnipeg	Manitoba
United States	Radiant Research	Akron	Ohio
United States	Center for Marital and Sexual Health Inc.	Beachwood	Ohio
United States	Montana Health Research Institute	Billings	Montana
United States	QUEST Research Institute	Bingham Farms	Michigan
United States	Radiant Research	Birmingham	Alabama
United States	Women's Health Practice	Champaign	Illinois
United States	Radiant Research Inc.	Chandler	Arizona
United States	University of Virginia Center for Psychiatric Clinical Research	Charlottesville	Virginia
United States	Radiant Research Inc.	Chicago	Illinois
United States	Tampa Bay Medical Research Inc.	Clearwater	Florida
United States	Columbus Center for Women's Health Research	Columbus	Ohio
United States	Clinical Research of South Florida	Coral Gables	Florida
United States	Radiant Research Inc.	Dallas	Texas
United States	Downtown Women's Health Care	Denver	Colorado
United States	Radiant Research Inc.	Denver	Colorado
United States	Radiant Research Inc.	Edina	Minnesota
United States	Lillestol Research LLC	Fargo	North Dakota
United States	Clinical Physiology Associates	Fort Myers	Florida
United States	Thameside OB/GYN Centre	Groton	Connecticut
United States	Greater Hartford Women's Health Associates	Hartford	Connecticut
United States	Medical Affiliated Research Center Inc.	Huntsville	Alabama
United States	University of Florida - Jacksonville	Jacksonville	Florida
United States	Womens Clinic of Lincoln P.C.	Lincoln	Nebraska
United States	Maryland Center for Sexual Health	Lutherville	Maryland
United States	University Hospitals Case Medical Center	Mayfield Heights	Ohio
United States	Virginia Research Center	Midlothian	Virginia
United States	Clinical Research Associates, Inc	Nashville	Tennessee
United States	Columbia University School of Nursing	New York	New York
United States	Tidewater Physicians for Women	Norfolk	Virginia
United States	Radiant Reseach	Overland Park	Kansas
United States	Compass Research East LLC	Oviedo	Florida
United States	Clinical Research of Philadelphia LLC	Philadelphia	Pennsylvania
United States	Wake Research Associates LLC	Raleigh	North Carolina
United States	Atlanta North Gynecology, PC	Roswell	Georgia
United States	Texas Diabetes and Endocrinology	Round Rock	Texas
United States	Radiant Research Inc.	San Antonio	Texas
United States	San Antonio Psychiatric Research Center Dba Croft Group Research Center	San Antonio	Texas
United States	Medical Center for Clinical Research	San Diego	California
United States	San Diego Sexual Medicine	San Diego	California
United States	Women's Clincial Research Center	Seattle	Washington
United States	Quality of Life Medical Research Center	Tucson	Arizona
United States	Cincinnati Urogynecology Associates (TRIHEALTH)	West Chester	Ohio
United States	Center for Marital and Sexual Health of South Florida	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Acerus Pharmaceuticals Corporation

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Orgasms Over an 84 Day Period Compared to Placebo Over the Entire Treatment Period		84 days
Secondary	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)
Secondary	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
Secondary	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