| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Hypoactive sexual desire disorder |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10020933 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
1) To assess the efficacy of 300 mcg/day TTS in naturally menopausal women receiving approved transdermal estrogen or oral non-CEE with or without transdermal or oral progestogen. The primary efficacy endpoint will be measured by the change from Week 0 (baseline) to Week 24 in 4-week frequency of total satisfying episodes (intercourse and non-intercourse), as reported on the Sexual Activity Log (SAL).
2) To assess the safety of 300 mcg/day TTS as measured by collection of AEs (including androgenic AEs), androgenic assessments, lipid/lipoprotein and carbohydrate profiles, and other safety parameters. Serum concentrations of free and total testosterone, total estradiol, and SHBG will be determined. |
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| E.2.2 | Secondary objectives of the trial |
1) To assess the efficacy of 300 mcg/day TTS in naturally menopausal women not receiving hormone replacement therapy or receiving approved transdermal estrogen or oral non-CEE with or without transdermal or oral progestogen as measured by the following parameters:
- change from Week 0 (baseline) to Week 12 in 4-week frequency of total satisfying episodes (intercourse and non-intercourse), as reported on the SAL;
- change from Week 0 (baseline) to Week 12 and Week 24 in Sexual Desire as measured by Profile of Female Sexual Function (PFSF);
- change from Week 0 (baseline) to Week 12 and Week 24 in Personal Distress as measured by the Personal Distress Scale (PDS);
- change from Week 0 (baseline) to Week 12 and Week 24 in the other domains of the PFSF; and
- change from Week 0 (baseline) to Week 12 and Week 24 in the other total SAL endpoints (frequency of total sexual episodes and the frequency of orgasms from total sexual episodes).
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Women will be screened for study participation according to the following inclusion criteria at Week –4. Eligible women must:
a) be 40 to 70 years old and in general good health based on medical history, physical examination, and laboratory evaluation;
b) have no spontaneous menstrual periods for 1 year (if post-hysterectomy, the woman must have at least 1 ovary. For hysterectomised women < 50 years of age, a screening follicle stimulating hormone [FSH] level > 30 IU/L is required to confirm
menopausal status (a previously documented FSH level in the clinical notes of
> 30 IU/L confirming the menopausal transition will also be acceptable);
c) be receiving a stable dose of an approved systemic transdermal estrogen or oral non-CEE (estrogen implants are not acceptable), if hysterectomised, or an approved
continuous systemic transdermal estrogen or oral non-CEE plus transdermal or oral
progestogen, if not hysterectomised, for at least 12 weeks prior to screening with the intention of maintaining that regimen throughout the study or not currently receiving any hormone replacement therapy (having stopped hormone replacement therapy at least 12 weeks before screening) with the intention of not starting hormone replacement therapy during the study;
d) have a clinically acceptable screening bilateral mammogram (no evidence of malignancy) as determined by a local radiologist. A clinically acceptable mammogram is one in which the report requests a follow-up in the standard timeframe. A documented result of a previous mammogram done up to 1 year prior to screening is acceptable; for clinical sites in Germany, a screening bilateral mammogram by a local radiologist will not be performed; only documented results from a previous mammogram done up to 1 year prior to screening will be used to assess eligibility;
e) have a clinically acceptable Pap smear (no evidence of malignancy or squamous intraepithelial lesions) if the cervix is present. A Pap smear at study entry may be performed on patients without a cervix at the discretion of the investigator;
f) be, in their own judgment, in a stable monogamous sexual relationship that is perceived to be secure and communicative, for at least 1 year prior to study entry. The relationship must be with the same partner who is sexually functional, both psychologically and physically; and is expected to be physically present (i.e., available for sexual activity at some time during a 24-hour day) at least 50% of each month during the 4-week pretreatment and 24-week efficacy treatment period of the study;
g) be able and willing to participate in the study as evidenced by providing written informed consent;
h) answer affirmatively to ALL of the following questions:
1. Before your menopause, would you say that in general, your sex life was good and satisfying?
2. Since your menopause, do you feel you have experienced a meaningful loss in your level of desire for sex?
3. Since your menopause, do you feel you have experienced a significant decrease in your sexual activity?
4. Are you concerned about or bothered by your current level of desire for or interest in sex?
5. Would you like to see an increase in your level of interest in or desire for sex and sexual activity?
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| E.4 | Principal exclusion criteria |
Women will be screened for study participation according to the following exclusion criteria at Week –4 or as specified. Eligible women must not:
a) have dyspareunia not alleviated by lubricants, any physical limitations, or sexual trauma that would interfere with normal sexual function;
b) have received marketed or investigational oral, sub-lingual, topical, transdermal injectable, or vaginal androgen therapy at any time during the past 3 months, or investigational implantable androgen therapy at any time during the past 7 months;
c) have received anti-androgen therapy or topical minoxidil for androgenic alopecia within the last 5 years;
d) have used within the last 12 weeks any of the following medications/preparations that may affect sexual function or otherwise interfere with interpretation of the study results: systemic corticosteroids (acute use for less than 7 days is accepted), non-selective and selective serotonin reuptake inhibitors, tricyclic anti-depressants, systemic beta-blockers , anti-adrenergics, spironolactone, apomorphine, PDE5 inhibitors (e.g., Viagra), tibolone, or selective estrogen receptor modulators, including tamoxifen;
e) have occasionally used (averaging more than once a week) in the past 30 days the following preparations that may interfere with interpretation of the study results: dehydroepiandrosterone (DHEA) or other drugs or supplements that may, in the opinion of the Investigator, affect sexual function;
f) have used tablet or powder forms of phytoestrogens for less than 12 weeks prior to Week –4. Stable use of phytoestrogens for 12 weeks or longer is acceptable, but should be maintained during the study period;
g) be experiencing any chronic or acute life stress relating to any major life change, such as recent loss of income or the death of a close family member, that may, in the opinion of the Investigator, significantly interfere with sexual activity;
h) have significant psychiatric disorder (including mild depressive disorder), a significant alcohol or drug dependency and/or be receiving pharmacologic treatment for such illness or disorder. For countries using the Beck Depression Inventory II (BDI-II), patients will be excluded if they have a score equal or larger than 14. For Germany, patients will be excluded if they have a score equal or larger than 10 on the BDI-I;
i) have current severe dermatological problems (e.g., severe or cystic acne), including concomitant skin disease or history of drug-induced contact dermatitis;
j) have a known or suspected hypersensitivity or allergy to any adhesive or any of the constituents of the transdermal systems;
k) have participated in a cumulative irritation test within the past 12 weeks;
l) have participated in a clinical trial or received an investigational medication within 30 days (exception: women participating in non-treatment observational studies may be included);
m) have evidence of clinically significant organic disease on the history and/or physical examination that would, in the opinion of the Investigator, put the patient at risk, prevent the patient from completing the study, or otherwise affect the outcome of the study;
n) have a history of breast cancer or estrogen-dependent neoplasia (e.g., endometrial cancer) or any gynecological cancer at any time before study entry or other cancer (except basal or squamous cell carcinoma) within the last 5 years;
o) have had gynecological or breast surgery within the last 6 months;
p) have acute liver or renal disease, or any other major illness which has occurred within the last 6 months;
q) have diabetes mellitus;
r) have had active gallbladder disease during the last 6 months;
s) have a history of cerebrovascular disease, thrombo-embolic disorders, myocardial infarction, or angina at anytime before study entry or thrombo-phlebitis within the last 5 years;
t) have an abnormal thyroid-stimulating hormone (TSH) value at screening confirmed by a free T4 outside the normal laboratory range (patients with an abnormal TSH, normal free T4, and no clinical signs or symptoms of thyroid disease, with or without replacement treatment, may be admitted to the study);
u) have, in the opinion of the Investigator, clinically significant abnormal pretreatment laboratory parameters (a single, repeat assay will be allowed if an assay result is questionable); or
v) have the following abnormal pretreatment laboratory parameters (a single repeat will be allowed if an assay result is questionable):
- Serum creatinine > 2.5 mg/dL
- Serum total bilirubin > 2 times the upper limit of normal
- Alanine aminotransferase (ALT) or aspartate aminotransferase - more than 3 times the upper limit of normal.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy:
The primary efficacy endpoint will be measured by the change from Week 0 (baseline) to Week 24 in 4-week frequency of total satisfying episodes (intercourse and non-intercourse), as reported on the Sexual Activity Log (SAL).
The SAL captures sexual activity on a weekly basis (Week -4 to Week 0 and Week 1 to Week 24), based on the following parameters:
1. the frequency of sexual intercourse,
2. the frequency of orgasms from episodes of sexual intercourse,
3. the frequency of satisfying episodes of sexual intercourse,
4. the frequency of sexual activity that did not include sexual intercourse,
5. the frequency of orgasms from episodes of sexual activity that did not include sexual intercourse, and
6. the frequency of satisfying episodes of sexual activity that did not include sexual intercourse.
Safety:
The primary safety endpoints wll be measured by collection of AEs (including androgenic AEs), androgenic assessments (Hirsutism, frequency of facial depilation and facial acne vulgaris) , lipid/lipoprotein and carbohydrate profiles, skin appearance at the most recently removed abdominal application sites, physical examination (including breast and pelvic examination). Serum concentrations of free and total testosterone, total estradiol, and SHBG will be determined.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 24 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| The study is considered terminated upon completion of all patient treatments and evaluations. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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