A two part study to a) investigate the reproducibility of the vaginal photoplethysmography (VPP) technique in healthy post-menopausal volunteers and subjects suffering from Female Sexual Arousal Disorder (FSAD) and b) a randomised double blind, placebo controlled 4-way crossover study to investigate the effect of single oral doses (10, 50 and 400mg) of UK-447,841 on vaginal blood flow in post-menopausal subjects suffering from FSAD. - N/A

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2004-001379-20-SE
• Date of registration: 02/08/2004
• Prospective Registration: Yes
• Primary sponsor: Pfizer AB
• Public title: A two part study to a) investigate the reproducibility of the vaginal photoplethysmography (VPP) technique in healthy post-menopausal volunteers and subjects suffering from Female Sexual Arousal Disorder (FSAD) and b) a randomised double blind, placebo controlled 4-way crossover study to investigate the effect of single oral doses (10, 50 and 400mg) of UK-447,841 on vaginal blood flow in post-menopausal subjects suffering from FSAD. - N/A
• Scientific title: A two part study to a) investigate the reproducibility of the vaginal photoplethysmography (VPP) technique in healthy post-menopausal volunteers and subjects suffering from Female Sexual Arousal Disorder (FSAD) and b) a randomised double blind, placebo controlled 4-way crossover study to investigate the effect of single oral doses (10, 50 and 400mg) of UK-447,841 on vaginal blood flow in post-menopausal subjects suffering from FSAD. - N/A
• Date of first enrolment: 28/09/2004
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-001379-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
All subjects
1. Post-menopausal female subjects aged 45-65
2. Post-menopausal status is defined by a documented history of:
a) Naturally amenorrhoeic for > 1 year or
b) A six month history of amenorrhoeic and an FSH level of > 50IU/L and serum estradiol < 20pg/ml or
c) Bilateral oophorectomy ord) Subjects who are surgically menopausal
3. Subjects must personally sign and date the informed consent documentation indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the trial.
4. Subjects must have been taking Hormone Replacement Therapy (HRT) at a stable dose for at least 3 months. This stable dose must be maintained throughout the duration of the study. (The exception is subjects who have already been on systemic HRT and who have switched to a new brand type. They will only need to establish stable use for 1 month). HRT is defined as any estrogenic hormonal medication administered alone or in combination with progesterone/ progestogens and/or androgens. Subjects will only be included if the supplement has been prescribed for an approved indication, the delivery route is approved and a reliable assay is available to ensure resultant hormone levels are not supra-physiologic. Specifically: -Testosterone replacement for libido enhancement, methyl-testosterone supplements and testosterone creams are excluded; Phytestrogens are not considered conventional HRT. Subjects currently using phytestrogens (e.g. Dong Quoi, Evening Primrose, Mexican Yams, Black Cohash, etc.,) may continue their use during the study as long as they maintain the same level of ingestion.
5. Subjects must have been in a stable heterosexual relationship for at least 3 months prior to study start and must remain in a stable relationship throughout the duration of the study.
6. Subjects must be willing and able to comply with scheduled visits, laboratory tests and opther trial procedures. FSAD subject group
7. Subjects must suffer from FSAD that has been present for at least 6 months prior to study entry which may or may not be associated with female orgasmic disorder and/or superficial/introital dyspareunia.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
All subjects
1. Subjects who have an estradiol plasma concentration of less than 40pg/mL. (N.B. those subjects taking HRT in the form of conjugated estrogens are not required to have a minimum estradiol concentration of 40 pg/mL, provided that in the opinion of the investigator they are clinically estradiol replete, e.g. vasomotor symptoms controlled and reversal or absence of vulval / vaginal atrophy).
2. Subjects who have a free plasma testosterone concentration <0.9pg/mL.
3. Subjects who are currently taking a selected estrogen receptor modulator (SERM), such as raloxifen or tamoxifen.
4. Subjects with a recent (past 6 months) history of alcohol or controlled substance abuse.
5. Subjects with recent (past 3 months) exacerbation of pelvic inflammatory disease, a recent untreated vaginal infection, salpingitis, or other severe or chronic gynecologic disease.
6. Subjects who have had previous surgery to the vagina (including that for stress incontinence or vaginal hysterectomy) and those who have any anatomical abnormality of the vagina.
7. Subjects who have a history of gynaecological malignancy or those with recent abnormal cervical cytology suggestive of neoplastic changes.
8. Subjects who drink more than 21 units of alcohol per week. (1 unit = 285mls of beer or 25ml of spirits or 125ml of wine).
9. Subjects with a history of involuntary movement disorders.
10. Subjects with any clinically significant abnormality following review of pre-study laboratory data and full physical examination.
11. Subjects who, in the opinion of the PI, have any medical or psychological condition or social circumstances which would impair their ability to participate reliably in the study, or who may increase the risk to themselves or others by participating.
12. In the opinion of the investigator, a subject who is not likely to complete the study for what ever reason.FSAD subject group
13. Subjects who suffer from HSDD as determined by the SFQ and subsequent semi-structured interview.
14. Subjects whose sexual dysfunction is considered to be situational, i.e. limited to certain types of stimulation, situation or specific partners.
15. Subjects who have significant dyspareunia, which is due to an inflammatory or anatomical condition (e.g. pelvic inflammatory disease, vulvovestibulitis, fibroids).
16. Subjects who have received treatment for any major psychiatric disorder (e.g. psychosis or hospitalization due to major depression) within the past 12 months. Subjects on SSRIs (selective serotonin re-uptake inhibitors), SNRIs (selective noradrenaline reuptake inhibitors), Tricyclic antidepressants as well as buproprion.
17. Subjects who are currently receiving medication known to interact with NEP-inhibitors such as ACE inhibitors. (This criterion will only apply to subjects recruited for Part B of the study.)
18. Subjects who suffers from hypo– or hypertension (treated as well as untreated) or have a resting supine blood pressure below 90/45mmHg or above 140/90 or who show a postural drop in either systolic blood pressure of >20mmHg and diastolic blood pressure of >10mmHg at screening. (This criterion will only apply to subjects recruited for Part B of the study.)
19. Subjects with any other major psychological or sexual disorder, not otherwise listed in the inclusion criteria, which is considered to be the primary diagnosis explaining the sexual dysfunction.
20. Subjects with otherwise treatable causes of FSAD including inadequately controlled diabetes, t

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Female Sexual Arousal Disorder (FSAD)
Classification code 10062641

Intervention(s)

Product Name: N/A
Product Code: UK-447,841
Pharmaceutical Form: Powder for oral solution
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: UK-447.841
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-400
Pharmaceutical form of the placebo: Powder for oral solution
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Part A:
VPA mean change from baseline to mean VSS as measured by VPP.
VPA mean change from baseline to maximum level during VSS as measured by VPP.

Part B:
VPA mean change from pre-dose baseline to mean VSS as measured by VPP.
VPA mean change from pre-dose baseline to maximum level during VSS as measured by VPP.

Main Objective: Part A: Primary: To investigate the reproducibility of the vaginal photoplethysmography (VPP) technique in healthy post-menopausal female volunteers and post-menopausal subjects suffering from FSAD.
Part B: Primary: To investigate the effect of single doses of UK-447,841 on vaginal blood flow (VBF) as measured by VPP in post-menopausal subjects suffering from FSAD.

Secondary Objective: Part A: To assess the degree of undesirable artefacts and fluctuations in the vaginal pulse amplitude (VPA) traces. To assess the variability of subjective feeling of arousal at baseline and during visual sexual stimulation (VSS). To investigate differences in VPA between healthy volunteers and subjects suffering from FSAD.

Part B: To investigate the suitability of this technique in determining sensitivity to change on VBF following dosing with UK-447,841.To assess the correlation between changes in VPA and subjective feeling of arousal during sexual arousal.To investigate the safety and toleration of single oral doses of UK-447,841 in FSAD subjects.To determine plasma concentrations of UK-447,841 in FSAD subjects. To determine the effect of UK-447,841 on levels of plasma biomarkers such as VIP, ANP, big endothelin and cGMP.

Secondary ID(s)

A5031004

N/A