This clinical trial is being performed to evaluate the efficacy of a single dose of TBS-2 on the occurence of orgasm. This study will explore the effect of TBS-2 on inducing an orgasm following sexual stimuli in anorgasmic female subjects at four…
ID
Source
Brief title
Condition
- Sexual dysfunctions, disturbances and gender identity disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary end-point:
- To evaluate the effect of a single dose of TBS-2 (1.2 mg) on the occurrence
of orgasm at 0.5, 2.0, 4.0 and 8.0 hours post-dose in females suffering from
primary or secondary anorgasmia .
The study will evaluate the occurrence of orgasm following vibrotactile
stimulation and visual sexual stimulation (VTS/VSS). The occurrence of orgasm
will be evaluated based on subject self-report. The subject is required to
press a button to indicate orgasm start.
Secondary outcome
Secondary end-points:
a) To evaluate the effect of a single dose of TBS-2 (1.2 mg) on time to orgasm
(TTO) at 0.5, 2.0, 4.0 and 8.0 hours post-dose in female subjects with primary
or secondary anorgasmia .
TTO will be recorded as the time from onset of VTS/VSS stimulation until the
start of orgasm at which time the subject will press a button so that TTO will
be automatically recorded by the computer program.
b) To evaluate the effect of a single dose of TBS-2 (1.2 mg) on quality of
orgasm at 0.5, 2.0, 4.0 and 8.0 hours post-dose in female subjects with primary
or secondary anorgasmia .
Quality of orgasm will be assessed by Quality of Orgasm
Questionnaire
c) To assess the safety of TBS-2.
The following close-out parameters will be compared to the baseline results:
- Vital Signs: blood pressure, body temperature, respiratory rate, heart rate.
- Hematology: CBC, hemoglobin and hematocrit values.
- Clinical Chemistry Profile - Na/K, glucose, urea, creatinine, calcium,
phosphate, uric acid, total bilirubin, albumin, AST, ALT, ALP, GGT, CK, LDL,
HDL, triglycerides.
- Thyroid panel - TSH, total and free tri-iodothyronine, total and free
thyroxine.
- Hormone Profile - Estradiol, Free Testosterone, Free Testosterone (percent),
Follicle Stimulating Hormone, Luteinizing Hormone, Prolactin, Progesterone, Sex
Hormone Binding Globulin, Total Testosterone, Dehydroepiandrosterone Sulfate
- Urinalysis - Urine specific gravity, glucose, protein, ketone, pH, bilirubin,
urobilinogen, nitrite, erythrocytes and leukocytes.
- Adverse events
Background summary
Anorgasmia is the second most frequently reported women*s sexual problem after
hypoactive sexual desire disorder. The Global Survey of Sexual Attitudes and
Behaviours (Laumann et al., 2005) assessed sexual problems in 9,000 women aged
40-80 years in 29 countries. The prevalence of *inability to reach orgasm*
ranged from 17.7% ( in Northern Europe) to 41.2% (in Southeast Asia).
Anorgasmia is considered to be the persistent or recurrent delay in, or absence
of, orgasm following a normal sexual excitement phase, causing marked distress
or interpersonal difficulty (DSM IV). When a woman has sexual activity that is
not accompanied by good quality orgasmic release, sexual activity may become a
chore or a duty rather than a mutually satisfying, intimate experience. This
may also lead to secondary loss of sexual interest and/or interpersonal
difficulties.
It is hypothesized that testosterone has central and peripheral effects on
sexual function. Testosterone, the primary circulation androgen in women, is a
naturally occurring steroid secreted by the ovaries and the adrenal glands.
Contrary to the sudden drop in oestrogen during menopause, serum levels of
androgens fall gradually as women age primarily due to a decrease in the
production of adrenal androgen precursors (Goldstat, 2003). Testosterone plays
a role in mood, body composition, bone mineral density and has central and
peripheral effects on sexual function (Davis 1999, Goldstat 2003). In the
periphery, testosterone is required for nitric oxide to stimulate
vasocongestion for the engorgement of clitoral tissue and vaginal lubrication
during sexual arousal.
Central effects are less well characterized. Testosterone stimulates dopamine
release in various brain structures implicated in motivation and reward
systems, including sexual desire. Testosterone was found to stimulate dopamine
release in the medial preoptic area of the anterior hypothalamus under basal
conditions and with sexual stimulation in rats (Halaris 2003). An fMRI study
in healthy women of different ages showed a testosterone level dependent
modulation of amygdala activity, suggesting that an age-related decline in
androgen levels contribute to the decrease in amygdala reactivity. Decreased
amygdala reactivity in older women could be restored to levels of young women
with intranasal exogenous testosterone (van Wingen et al, 2009). Exogenous
intranasal testosterone thus may enhance healthy sexual functioning through
complex brain mechanisms.
Over the two past decades, over 80 studies have been conducted in women showing
benificial effects of testosterone on sexual desire, arousal, frequency of
satisfactory sexual activity, pleasure and responsiveness (Traish (review
2009)).
The product under investigation in this study, TBS-2, is a testosterone
intranasal gel. Contrary to the other routes of administration, administration
of the bioadhesive TBS-2 through the nasal route allows for direct uptake of
testosterone into the brain and rapid absorption into systemic circulation
(Banks et al. 2009). The delivery of testosterone to the brain and systemic
absorption is hypothesized to be effective in enhancing sexual desire and
orgasm. In addition, TBS-2 may prove effective in alleviating anorgasmia in
an "as needed" way, thus avoiding chronic exposure to testosterone.
Study objective
This clinical trial is being performed to evaluate the efficacy of a single
dose of TBS-2 on the occurence of orgasm.
This study will explore the effect of TBS-2 on inducing an orgasm following
sexual stimuli in anorgasmic female subjects at four different time points
post-dose. Pharmacodynamic efficacy will be evaluated using vibrotactile
stimulation (VTS) in combination with visual sexual stimulation (VSS). The
VTS/VSS procedure was tested in a pilot study in women (Laan & van Lunsen,
2002) and showed that VTS in combination with visual sexual stimulation (VSS)
reliably could trigger orgasm in healthy female volunteers with no
self-reported difficulties in achieving orgasm. Time to orgasm (TTO) showed an
acceptable intra-subject variability. In the present study, a similar clitoral
vibrator will be used.
Study design
Single-center randomized, single-blind placebo-controlled five-arm parallel
group study.
This study consists of two parts: Part I - sexual stimulation without
medication and Part II - sexual stimulation with TBS2/Placebo single-dose
treatment. In case subjects did not reach orgasm during the sexual stimulation
in Part I they may continue with Part II. In Part II, subjects will be
randomized to receive a single dose of TBS-2 or Placebo and be subjected to
VTS/VSS 0.5 hour post-dose in placebo arm or 0.5, 2.0, 4.0 or 8.0 hours
post-dose in TBS-2 treatment arms. There will be at least 5-7 days between Part
I and Part II.
Intervention
Subjects receive one dose (1.2 mg) of TBS-2 at visit 3
Study burden and risks
Risks
The risks to female subjects in this study are minimal. Subjects will be
recieving a single dose 0.9 mg of TBS-2.
Testosterone in approved for women in the form of a patch, Intrinsa. Following
48 weeks of administration, common side effects included hirsutism and
reactions at the site of application of the patch (which is not applicable for
our product).
Benefits
The product under investigation in this study, TBS-2, is a testosterone
intranasal gel. Contrary to the other routes of administration, administration
of the bioadhesive TBS-2 through the nasal route allows for direct uptake of
testosterone into the brain and rapid absorption into systemic circulation
(Banks et al. 2009). TBS-2 has been shown to influence the amygdale. The
delivery of testosterone to the brain and systemic absorption is hypothesized
to be effective in enhancing sexual desire and orgasm. In addition, TBS-2 may
prove effective in alleviating anorgasmia in an "as needed" way, thus avoiding
chronic exposure to testosterone.
Suite B, Durants Business Centre, Durant,
Christ Church BB17097
AU
Suite B, Durants Business Centre, Durant,
Christ Church BB17097
AU
Listed location countries
Age
Inclusion criteria
Females aged 18 - 50 years
Anorgasmia
Premenopausal
BMI equal or less than 35
Exclusion criteria
History of any clinically relevant other psychiatric disorder that could impact sexual function
History of Major Depressive Disorder within six (6) months prior to study
Subjects who meet DSM-IV criteria (APA) for Sexual Aversion Disorder, Substance-Induced Sexual Dysfunction, Dyspareunia (not caused by inadequate foreplay stimulation or alleviated by lubricants), Vaginismus, Gender Identity Disorder, Paraphilia, or for Sexual Dysfunction Due to a General Medical Condition.
Patients with pelvic inflammatory disease, urinary tract or vaginal infection
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-023559-27-NL |
| CCMO | NL34768.018.10 |