Hypoactive Sexual Desire Disorder
Conditions
Keywords
Natural Menopause
Brief summary
This study is designed to evaluate the endometrial safety of a testosterone patch as treatment for low libido in naturally postmenopausal women.
Detailed description
Naturally postmenopausal women with hypoactive sexual desire disorder (HSDD) will be randomized into a 52-week, multicenter, double-blind (DB), parallel-group, placebo-controlled study. Patients will be stratified based on whether they use concomitant estrogen/progestin therapy and then randomized in a 4:1 ration to receive either testosterone transdermal system (300 mcg/day) or placebo. Patients using estrogen/progestin at the start of the study should maintain this therapy throughout the study; patients not using estrogen/progestin at the start of the study should not initiate estrogen/progestin therapy throughout the study. Endometrial biopsies and transvaginal ultrasounds will be collected/performed at screening and study exit for all patients. Safety will be assessed by adverse events, reports of vaginal bleeding, lipids, serum chemistry, and hematology. Physical exams, pap smears, and mammograms will be monitored.
Interventions
Testosterone patch, 300 mcg/day, change patch twice a week for 52 weeks
DRUGPlacebo patch
placebo patch, changed twice a week for 52 weeks
Sponsors
Warner Chilcott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Women will be screened for study participation and must be at least one year post menopausal, 45-70 years old, in general good health, and may or may not be on hormone therapy, and must have low sexual desire which causes distress.
Exclusion criteria
* Women will be screened for study participation and must not be using androgen therapy or have any medical, physical, psychological, or pharmacological condition that could make participation unsafe or confound the safety evaluation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Endometrial Hyperplasia in Naturally Postmenopausal Women With Hypoactive Sexual Desire Disorder (HSDD) Not Using Concomitant Estrogen and Progestin, Year 1 | 52 weeks | Incidence measured is number of patients with endometrial hyperplasia/number of patients with evaluable biopsies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Endometrial Hyperplasia in Naturally Postmenopausal Women With HSDD Using Concomitant Estrogen and Progestin, Year 1 | 52 weeks | Incidence measured is number of patients with endometrial hyperplasia/number of patients with evaluable biopsies |
| Incidence Endometrial Hyperplasia in Naturally Postmenopausal Women With HSDD Using Concomitant Estrogen & Progestin Combined With Those Not Using Estrogen & Progestin Therapy, Year 1 | 52 weeks | Incidence measured is number of patients with endometrial hyperplasia/number of patients with evaluable biopsies |
Countries
United States
Participant flow
Recruitment details
Screening began 14 May 2007
Pre-assignment details
Randomized 1127 women not using concomitant estrogen & progestin (E&P) therapy. An additional 134 women using concomitant estrogen & progestin therapy were randomized. Subjects were stratified by using or not using E&P by site and then randomized 4:1 300 mcg/d TTS or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo patch | 251 |
| Testosterone Testosterone patch, 300 mcg/day, change patch twice a week for 52 weeks | 1,020 |
| Total | 1,271 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 24 | 90 |
| Overall Study | Lost to Follow-up | 14 | 34 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 7 |
| Overall Study | Site Closed | 2 | 1 |
| Overall Study | Withdrawal by Subject | 34 | 108 |
Baseline characteristics
| Characteristic | Placebo | Testosterone | Total |
|---|---|---|---|
| Age Continuous | 55.5 years STANDARD_DEVIATION 4.8 | 55.8 years STANDARD_DEVIATION 4.9 | 55.7 years STANDARD_DEVIATION 4.9 |
| Age, Customized 40-49 years old | 21 Participants | 95 Participants | 116 Participants |
| Age, Customized 50-59 years old | 182 Participants | 700 Participants | 882 Participants |
| Age, Customized 60-65 years old | 39 Participants | 189 Participants | 228 Participants |
| Age, Customized 66 + years old | 9 Participants | 35 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 50 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 237 Participants | 969 Participants | 1206 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian (Oriental) | 3 Participants | 6 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 9 Participants | 82 Participants | 91 Participants |
| Race/Ethnicity, Customized Caucasian | 231 Participants | 920 Participants | 1151 Participants |
| Race/Ethnicity, Customized Hawaiian / Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Indian (American) | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Indian (Asian) | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Latino | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Mexican | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Multi-Racial | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Spanish | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 251 participants | 1020 participants | 1271 participants |
| Sex: Female, Male Female | 251 Participants | 1020 Participants | 1271 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 125 / 251 | 472 / 1,019 |
| serious Total, serious adverse events | 10 / 251 | 33 / 1,019 |
Outcome results
Primary
Incidence of Endometrial Hyperplasia in Naturally Postmenopausal Women With Hypoactive Sexual Desire Disorder (HSDD) Not Using Concomitant Estrogen and Progestin, Year 1
Incidence measured is number of patients with endometrial hyperplasia/number of patients with evaluable biopsies
Time frame: 52 weeks
Population: Subjects with evaluable endometrial biopsies.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of Endometrial Hyperplasia in Naturally Postmenopausal Women With Hypoactive Sexual Desire Disorder (HSDD) Not Using Concomitant Estrogen and Progestin, Year 1 | 0 # Endometrial Hyperplasia/Evaluable Biop |
| Testosterone | Incidence of Endometrial Hyperplasia in Naturally Postmenopausal Women With Hypoactive Sexual Desire Disorder (HSDD) Not Using Concomitant Estrogen and Progestin, Year 1 | 0 # Endometrial Hyperplasia/Evaluable Biop |
Comparison: 1000 naturally postmenopausal women not on concomitant E+P therapy at baseline were to be randomized (800 TTS; 200 placebo). It was assumed 60% would complete 1 year and 80% of these would have evaluable biopsies. Of the 800 randomized to TTS approximately 380 were expected to have evaluable biopsies at 1 year. 380 patients on TTS with evaluable biopsies at 1 year would provide 90% power to rule out an incidence of hyperplasia of 2% using the upper bound of a 2-sided 95% CI.p-value: 1Fisher Exact
Secondary
Incidence Endometrial Hyperplasia in Naturally Postmenopausal Women With HSDD Using Concomitant Estrogen & Progestin Combined With Those Not Using Estrogen & Progestin Therapy, Year 1
Incidence measured is number of patients with endometrial hyperplasia/number of patients with evaluable biopsies
Time frame: 52 weeks
Population: Subjects with evaluable endometrial biopsies.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence Endometrial Hyperplasia in Naturally Postmenopausal Women With HSDD Using Concomitant Estrogen & Progestin Combined With Those Not Using Estrogen & Progestin Therapy, Year 1 | 0 # Endometrial Hyperplasia/Evaluable Biop |
| Testosterone | Incidence Endometrial Hyperplasia in Naturally Postmenopausal Women With HSDD Using Concomitant Estrogen & Progestin Combined With Those Not Using Estrogen & Progestin Therapy, Year 1 | 0 # Endometrial Hyperplasia/Evaluable Biop |
Comparison: 1000 naturally postmenopausal women not on concomitant E+P therapy at baseline were to be randomized (800 TTS; 200 placebo). It was assumed 60% would complete 1 year and 80% of these would have evaluable biopsies. Of the 800 randomized to TTS approximately 380 were expected to have evaluable biopsies at 1 year. 380 patients on TTS with evaluable biopsies at 1 year would provide 90% power to rule out an incidence of hyperplasia of 2% using the upper bound of a 2-sided 95% CI.p-value: 1Fisher Exact
Secondary
Incidence of Endometrial Hyperplasia in Naturally Postmenopausal Women With HSDD Using Concomitant Estrogen and Progestin, Year 1
Incidence measured is number of patients with endometrial hyperplasia/number of patients with evaluable biopsies
Time frame: 52 weeks
Population: Subjects with evaluable endometrial biopsies.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of Endometrial Hyperplasia in Naturally Postmenopausal Women With HSDD Using Concomitant Estrogen and Progestin, Year 1 | 0 # Endometrial Hyperplasia/Evaluable Biop |
| Testosterone | Incidence of Endometrial Hyperplasia in Naturally Postmenopausal Women With HSDD Using Concomitant Estrogen and Progestin, Year 1 | 0 # Endometrial Hyperplasia/Evaluable Biop |
Comparison: 1000 naturally postmenopausal women not on concomitant E+P therapy at baseline were to be randomized (800 TTS; 200 placebo). It was assumed 60% would complete 1 year and 80% of these would have evaluable biopsies. Of the 800 randomized to TTS approximately 380 were expected to have evaluable biopsies at 1 year. 380 patients on TTS with evaluable biopsies at 1 year would provide 90% power to rule out an incidence of hyperplasia of 2% using the upper bound of a 2-sided 95% CI.p-value: 1Fisher Exact