Atrophy, Vaginal Diseases
Conditions
Keywords
Urogenital atrophy, Menopausal symptoms, Vulvar and vaginal atrophy in postmenopausal women, Vaginal atrophy
Brief summary
The purpose of this study is to determine the efficacy and long-term safety of 60mg ospemifene in the treatment of VVA in postmenopausal women with intact uterus.
Interventions
DRUGOspemifene 60 mg
60 mg/day (QD) dose of ospemifene (1 tablet) will be taken for 52 weeks - from Visit 2 (Randomization, Day 1) to Visit 6 (End of Therapy or Early Discontinuation, Week 52). Dosing will be oral and the ospemifene 60 mg tablet will be taken once daily, in the morning, with food.
DRUGPlacebo
Dosing will be oral and placebo will be taken once daily, in the morning, with food for 52 weeks - from Visit 2 (Randomization, Day 1) to Visit 6 (End of Therapy or Early Discontinuation, Week 52)
Sponsors
Hormos Medical
QuatRx Pharmaceuticals
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Naturally or surgically menopausal * Intact uterus * Vaginal pH greater than 5.0 * 5% or fewer superficial cells in maturation index of vaginal smear
Exclusion criteria
* Evidence of endometrial hyperplasia, cancer or other pathology * Abnormal Pap smear * Uterine bleeding of unknown origin or uterine polyps * Current vaginal infection requiring medication * Use of hormonal medications * Clinically significant abnormal gynecological findings other than signs of vaginal atrophy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Change From Baseline in Percentage of Parabasal Cells in Maturation Index of Vaginal Smear | 12 weeks |
| Mean Change From Baseline in Percentage of Superficial Cells in Maturation Index of Vaginal Smear | 12 weeks |
| Mean Change From Baseline in Vaginal pH | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Sex Hormone Binding Globulin Levels | 52 weeks |
| Change From Baseline in Estradiol Levels | 52 weeks |
| Visual Evaluation of the Vagina (Baseline & Week 52) | 52 weeks |
| Change From Baseline in Luteinizing Hormone Levels | 52 weeks |
| Change From Baseline in Follicle Stimulating Hormone Levels | 52 weeks |
Participant flow
Recruitment details
This was a multicenter study conducted at 23 centers in Belgium, Denmark, Finland, and Sweden. First subject was screened on Nov. 26, 2007 and last subjected completed the study on June 26, 2009
Participants by arm
| Arm | Count |
|---|---|
| Subjects on Ospemifene 60 mg/Day (Baseline) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks. | 363 |
| Subjects on Placebo (Baseline) Placebo was taken orally, once daily, in the morning, with food for 52 weeks. | 63 |
| Total | 426 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 48 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other-family problems & doctor's request | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 14 |
Baseline characteristics
| Characteristic | Subjects on Ospemifene 60 mg/Day (Baseline) | Subjects on Placebo (Baseline) | Total |
|---|---|---|---|
| Age, Continuous | 61.7 years | 62.9 years | 62.3 years |
| Alcohol | 2.4 drinks/week STANDARD_DEVIATION 3.4 | 2.3 drinks/week | 2.35 drinks/week STANDARD_DEVIATION 3.33 |
| BMI | 24.65 kg/m^2 | 24.11 kg/m^2 | 24.38 kg/m^2 STANDARD_DEVIATION 2.892 |
| Race/Ethnicity, Customized Asian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Caucasian | 361 participants | 63 participants | 424 participants |
| Region of Enrollment Belgium | 101 Participants | 18 Participants | 119 Participants |
| Region of Enrollment Denmark | 56 Participants | 9 Participants | 65 Participants |
| Region of Enrollment Finland | 177 Participants | 31 Participants | 208 Participants |
| Region of Enrollment Sweden | 29 Participants | 5 Participants | 34 Participants |
| Sex: Female, Male Female | 363 Participants | 63 Participants | 426 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 | 37 / 62 | 252 / 364 |
| serious Total, serious adverse events | 4 / 62 | 18 / 364 |
Outcome results
Primary
Mean Change From Baseline in Percentage of Parabasal Cells in Maturation Index of Vaginal Smear
Time frame: 12 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects on Placebo (Baseline) | Mean Change From Baseline in Percentage of Parabasal Cells in Maturation Index of Vaginal Smear | 5.0 percentage of parabasal cells | Standard Deviation 27.86 |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Mean Change From Baseline in Percentage of Parabasal Cells in Maturation Index of Vaginal Smear | -46.0 percentage of parabasal cells | Standard Deviation 41.96 |
Primary
Mean Change From Baseline in Percentage of Superficial Cells in Maturation Index of Vaginal Smear
Time frame: 12 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects on Placebo (Baseline) | Mean Change From Baseline in Percentage of Superficial Cells in Maturation Index of Vaginal Smear | 1.0 percentage of superficial cells | Standard Deviation 4.36 |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Mean Change From Baseline in Percentage of Superficial Cells in Maturation Index of Vaginal Smear | 10.3 percentage of superficial cells | Standard Deviation 12.53 |
Primary
Mean Change From Baseline in Vaginal pH
Time frame: 12 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects on Placebo (Baseline) | Mean Change From Baseline in Vaginal pH | -0.16 pH | Standard Deviation 0.945 |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Mean Change From Baseline in Vaginal pH | -1.21 pH | Standard Deviation 0.912 |
Secondary
Change From Baseline in Estradiol Levels
Time frame: 52 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects on Placebo (Baseline) | Change From Baseline in Estradiol Levels | 0.004 nmol/L | Standard Deviation 0.012 |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Change From Baseline in Estradiol Levels | 0.004 nmol/L | Standard Deviation 0.0145 |
Secondary
Change From Baseline in Follicle Stimulating Hormone Levels
Time frame: 52 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects on Placebo (Baseline) | Change From Baseline in Follicle Stimulating Hormone Levels | -7.63 U/L | Standard Deviation 17.083 |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Change From Baseline in Follicle Stimulating Hormone Levels | -19.69 U/L | Standard Deviation 18.977 |
Secondary
Change From Baseline in Luteinizing Hormone Levels
Time frame: 52 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects on Placebo (Baseline) | Change From Baseline in Luteinizing Hormone Levels | -0.88 U/L | Standard Deviation 7.738 |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Change From Baseline in Luteinizing Hormone Levels | -3.16 U/L | Standard Deviation 8.127 |
Secondary
Change From Baseline in Sex Hormone Binding Globulin Levels
Time frame: 52 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects on Placebo (Baseline) | Change From Baseline in Sex Hormone Binding Globulin Levels | -0.8 nmol/L | Standard Deviation 15.41 |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Change From Baseline in Sex Hormone Binding Globulin Levels | 31.0 nmol/L | Standard Deviation 27.16 |
Secondary
Visual Evaluation of the Vagina (Baseline & Week 52)
Time frame: 52 weeks
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-None | 10 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-Severe | 7 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-Moderate | 32 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-Mild | 18 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-Moderate | 23 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-Mild | 14 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-Severe | 2 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-Mild | 28 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-Moderate | 14 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-Moderate | 19 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-None | 7 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-Mild | 28 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-Severe | 11 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-Severe | 5 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-Moderate | 14 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-Severe | 5 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-None | 10 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-Mild | 31 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-None | 13 participants |
| Subjects on Placebo (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-None | 24 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-None | 22 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-None | 20 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-Mild | 12 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-Moderate | 21 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-None | 13 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-Severe | 5 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-Mild | 12 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-Severe | 5 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-None | 18 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-Mild | 17 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-Moderate | 16 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-Severe | 5 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-None | 17 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-Mild | 21 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-Moderate | 15 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-Severe | 3 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-Severe | 3 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-Mild | 21 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-Moderate | 17 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-Moderate | 17 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-Moderate | 95 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-None | 134 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-Mild | 147 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-Severe | 47 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-None | 76 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-Severe | 23 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-Mild | 118 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-Mild | 164 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-Moderate | 101 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-Moderate | 146 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-Severe | 21 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-None | 47 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-None | 74 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-Severe | 46 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-Moderate | 125 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-Severe | 24 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-None | 46 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-Mild | 110 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-Mild | 120 participants |
| Subjects on Ospemifene 60 mg/Day (Baseline) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-Moderate | 150 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-Mild | 35 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-Moderate | 15 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-Severe | 4 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-Moderate | 17 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-None | 232 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-Severe | 1 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-Severe | 1 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-Mild | 53 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-None | 243 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-None | 219 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-None | 242 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-Severe | 4 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-Moderate | 12 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-Mild | 52 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Pallor-Moderate | 11 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-Severe | 3 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Petechiae-Mild | 39 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal redness in the mucosa-Moderate | 22 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Vaginal dryness in the mucosa-Mild | 39 participants |
| Subjects on Ospemifene 60 mg/Day (Week 52) | Visual Evaluation of the Vagina (Baseline & Week 52) | Friability-None | 241 participants |