Trial Outcomes & Findings for Study to Evaluate Ospemifene in Patients With Moderate to Severe Vaginal Dryness Due to Menopause (NCT NCT02638337)

NCT ID: NCT02638337

Last Updated: 2019-04-02

Results Overview

Parabasal cells are immature squamous cells in the lining of the vagina. A predominance of parabasal cells indicates absence of estrogenic stimulation and vaginal atrophy. Vaginal smear samples were taken from the middle third of the lateral vaginal wall and were evaluated at a central laboratory by a qualified pathologist. A decrease in parabasal cells indicates improvement in vaginal atrophy. To calculate least squares (LS) means, a mixed-effects model for repeated measures (MMRM) model was used.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 631 participants
• Primary outcome timeframe: Baseline and Week 12
• Results posted on: 2019-04-02

Participant Flow

Participants were randomized at 68 sites in the United States.

After a screening period of up to 4 weeks, participants who met all eligibility criteria were randomized in a 1:1 ratio to receive either ospemifene 60 mg once daily or matching placebo for 12 weeks. Randomization was stratified by severity of most bothersome symptom of vaginal dryness on Day 1 and by the presence or absence of the uterus.

Participant milestones

Measure	Ospemifene Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Overall Study STARTED	316	315
Overall Study Received Treatment	313	315
Overall Study COMPLETED	283	279
Overall Study NOT COMPLETED	33	36

Reasons for withdrawal

Measure	Ospemifene Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Overall Study Adverse Event	6	10
Overall Study Protocol Violation	3	0
Overall Study Withdrawal by Subject	13	16
Overall Study Lost to Follow-up	7	7
Overall Study Other - Miscellaneous	4	3

Baseline Characteristics

Participants in the intent-to-treat population with available data

Baseline characteristics by cohort

Measure	Ospemifene n=313 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=314 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.	Total n=627 Participants Total of all reporting groups
Age, Continuous	59.7 years STANDARD_DEVIATION 6.6 • n=313 Participants	59.8 years STANDARD_DEVIATION 7.2 • n=314 Participants	59.7 years STANDARD_DEVIATION 6.9 • n=627 Participants
Age, Customized >= 40 to < 45 years	3 Participants n=313 Participants	7 Participants n=314 Participants	10 Participants n=627 Participants
Age, Customized >= 45 to < 55 years	66 Participants n=313 Participants	58 Participants n=314 Participants	124 Participants n=627 Participants
Age, Customized >= 55 to < 65 years	171 Participants n=313 Participants	174 Participants n=314 Participants	345 Participants n=627 Participants
Age, Customized >= 65 years	73 Participants n=313 Participants	75 Participants n=314 Participants	148 Participants n=627 Participants
Sex: Female, Male Female	313 Participants n=313 Participants	314 Participants n=314 Participants	627 Participants n=627 Participants
Sex: Female, Male Male	0 Participants n=313 Participants	0 Participants n=314 Participants	0 Participants n=627 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	84 Participants n=313 Participants	79 Participants n=314 Participants	163 Participants n=627 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	228 Participants n=313 Participants	234 Participants n=314 Participants	462 Participants n=627 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=313 Participants	1 Participants n=314 Participants	2 Participants n=627 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=313 Participants	7 Participants n=314 Participants	7 Participants n=627 Participants
Race/Ethnicity, Customized Asian	1 Participants n=313 Participants	3 Participants n=314 Participants	4 Participants n=627 Participants
Race/Ethnicity, Customized Black or African American	38 Participants n=313 Participants	32 Participants n=314 Participants	70 Participants n=627 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=313 Participants	0 Participants n=314 Participants	0 Participants n=627 Participants
Race/Ethnicity, Customized White	273 Participants n=313 Participants	266 Participants n=314 Participants	539 Participants n=627 Participants
Race/Ethnicity, Customized Other	1 Participants n=313 Participants	6 Participants n=314 Participants	7 Participants n=627 Participants
Presence of Uterus Yes	128 Participants n=313 Participants	132 Participants n=314 Participants	260 Participants n=627 Participants
Presence of Uterus No	185 Participants n=313 Participants	182 Participants n=314 Participants	367 Participants n=627 Participants
Current Hot Flashes Yes	26 Participants n=313 Participants	28 Participants n=314 Participants	54 Participants n=627 Participants
Current Hot Flashes No	287 Participants n=313 Participants	286 Participants n=314 Participants	573 Participants n=627 Participants
Previous Hormone Treatment as Prior Treatment None	305 Participants n=313 Participants	307 Participants n=314 Participants	612 Participants n=627 Participants
Previous Hormone Treatment as Prior Treatment Oral	5 Participants n=313 Participants	5 Participants n=314 Participants	10 Participants n=627 Participants
Previous Hormone Treatment as Prior Treatment Transdermal	0 Participants n=313 Participants	0 Participants n=314 Participants	0 Participants n=627 Participants
Previous Hormone Treatment as Prior Treatment Vaginal	4 Participants n=313 Participants	3 Participants n=314 Participants	7 Participants n=627 Participants
Previous Hormone Treatment as Prior Treatment Other	0 Participants n=313 Participants	0 Participants n=314 Participants	0 Participants n=627 Participants
Duration of Vulvovaginal Atrophy (VVA)	8.36 years STANDARD_DEVIATION 6.92 • n=313 Participants	8.98 years STANDARD_DEVIATION 7.79 • n=314 Participants	8.67 years STANDARD_DEVIATION 7.37 • n=627 Participants
Percentage of Parabasal Cells in the Vaginal Squamous Epithelium:	25.8 percentage of cells STANDARD_DEVIATION 33.3 • n=306 Participants • Participants in the intent-to-treat population with available data	28.3 percentage of cells STANDARD_DEVIATION 33.1 • n=308 Participants • Participants in the intent-to-treat population with available data	27.0 percentage of cells STANDARD_DEVIATION 33.2 • n=614 Participants • Participants in the intent-to-treat population with available data
Percentage of Superficial Cells in the Vaginal Squamous Epithelium	3.0 percentage of cells STANDARD_DEVIATION 7.6 • n=306 Participants • Participants in the intent-to-treat population with available data	2.8 percentage of cells STANDARD_DEVIATION 6.9 • n=308 Participants • Participants in the intent-to-treat population with available data	2.9 percentage of cells STANDARD_DEVIATION 7.2 • n=614 Participants • Participants in the intent-to-treat population with available data
Vaginal pH	6.11 pH STANDARD_DEVIATION 0.70 • n=313 Participants	6.14 pH STANDARD_DEVIATION 0.73 • n=314 Participants	6.12 pH STANDARD_DEVIATION 0.71 • n=627 Participants
Mean Severity of Most Bothersome Symptom of Vaginal Dryness	2.53 units on a scale STANDARD_DEVIATION 0.50 • n=313 Participants	2.54 units on a scale STANDARD_DEVIATION 0.50 • n=314 Participants	2.54 units on a scale STANDARD_DEVIATION 0.5 • n=627 Participants
Severity of Most Bothersome Symptom of Vaginal Dryness None	0 Participants n=313 Participants	0 Participants n=314 Participants	0 Participants n=627 Participants
Severity of Most Bothersome Symptom of Vaginal Dryness Mild	0 Participants n=313 Participants	0 Participants n=314 Participants	0 Participants n=627 Participants
Severity of Most Bothersome Symptom of Vaginal Dryness Moderate	148 Participants n=313 Participants	143 Participants n=314 Participants	291 Participants n=627 Participants
Severity of Most Bothersome Symptom of Vaginal Dryness Severe	165 Participants n=313 Participants	171 Participants n=314 Participants	336 Participants n=627 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available baseline data

Parabasal cells are immature squamous cells in the lining of the vagina. A predominance of parabasal cells indicates absence of estrogenic stimulation and vaginal atrophy.

Vaginal smear samples were taken from the middle third of the lateral vaginal wall and were evaluated at a central laboratory by a qualified pathologist.

A decrease in parabasal cells indicates improvement in vaginal atrophy. To calculate least squares (LS) means, a mixed-effects model for repeated measures (MMRM) model was used.

Outcome measures

Measure	Ospemifene n=306 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=308 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in the Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear at Week 12	-23.7 percentage of cells Standard Error 1.4	-1.9 percentage of cells Standard Error 1.4

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available baseline data

Superficial cells are mature squamous cells in the lining of the vagina that can decrease in number after menopause resulting in vulvovaginal atrophy.

Vaginal smear samples were taken from the middle third of the lateral vaginal wall and were evaluated at a central laboratory by a qualified pathologist.

An increase in the number of superficial cells indicates improvement in atrophy.

To calculate least squares (LS) means, a mixed-effects model for repeated measures (MMRM) model was used.

Outcome measures

Measure	Ospemifene n=306 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=308 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in the Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear at Week 12	7.8 percentage of cells Standard Error 0.7	0.6 percentage of cells Standard Error 0.7

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available baseline data

The pH scale ranges from 0 to 14. A pH of 7 is neutral, less than 7 is acidic, and greater than 7 is basic. A typical vaginal pH in women of reproductive age is between 3.5 and 4.5, increasing to > 4.5 after menopause.

Vaginal pH was measured by the investigator using a pH indicator strip at the middle third of the vaginal wall.

To calculate least squares (LS) means, a mixed-effects model for repeated measures (MMRM) model was used.

Outcome measures

Measure	Ospemifene n=313 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=314 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in the Vaginal pH at Week 12	-1.01 pH Standard Error 0.04	-0.29 pH Standard Error 0.04

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available baseline data

The severity of the most bothersome symptom of vaginal dryness was assessed by the participant through the VVA questionnaire as none = 0, mild = 1, moderate = 2, and severe = 3.

Outcome measures

Measure	Ospemifene n=313 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=314 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in the Severity of Self-reported Most Bothersome Symptom (MBS) of Vaginal Dryness at Week 12	-1.29 units on a scale Standard Deviation 1.01	-0.91 units on a scale Standard Deviation 0.96

PRIMARY outcome

Timeframe: From the first dose of study drug up to 14 days after the last dose; 14 weeks

Population: Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.

Treatment-related adverse events (AEs) were defined as AEs that were considered by the investigator to be related to investigational medicinal product, for which causal relationship with the study drug could be reasonably explained.

A serious adverse event (SAE) is defined as any AE occurring at any dose that resulted in any of the following outcomes:

• Death
• Life-threatening condition
• Hospitalization or prolongation of existing hospitalization for treatment
• Persistent or significant disability/incapacity
• Congenital anomaly/birth defect
• Other medically important conditions that, based on medical judgment, may jeopardize the participant's health and may require medical intervention to prevent one of the outcomes listed above.

Outcome measures

Measure	Ospemifene n=317 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=310 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Number of Participants With Adverse Events Any adverse event	112 Participants	103 Participants
Number of Participants With Adverse Events Treatment-related adverse events	28 Participants	20 Participants
Number of Participants With Adverse Events Adverse events leading to withdrawal	6 Participants	10 Participants
Number of Participants With Adverse Events Treatment-related AEs leading to withdrawal	5 Participants	3 Participants
Number of Participants With Adverse Events Serious adverse events	5 Participants	3 Participants
Number of Participants With Adverse Events Treatment-related serious adverse events	0 Participants	0 Participants
Number of Participants With Adverse Events Adverse events with outcome of death	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 4 and 8

Population: Intent-to-treat population with baseline data

Parabasal cells are immature squamous cells in the lining of the vagina. A predominance of parabasal cells indicates absence of estrogenic stimulation and vaginal atrophy. Vaginal smear samples were taken from the middle third of the lateral vaginal wall and were evaluated at a central laboratory by a qualified pathologist. A decrease in parabasal cells indicates improvement in vaginal atrophy.

Outcome measures

Measure	Ospemifene n=306 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=308 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in the Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear at Weeks 4 and 8 Week 4	-21.6 percentage of cells Standard Error 1.3	0.0 percentage of cells Standard Error 1.3
Change From Baseline in the Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear at Weeks 4 and 8 Week 8	-23.7 percentage of cells Standard Error 1.3	-1.9 percentage of cells Standard Error 1.3

SECONDARY outcome

Timeframe: Baseline and Weeks 4 and 8

Population: Intent-to-treat population with available baseline data

Superficial cells are mature squamous cells in the lining of the vagina that can decrease in number after menopause resulting in vulvovaginal atrophy. Vaginal smear samples were taken from the middle third of the lateral vaginal wall and were evaluated at a central laboratory by a qualified pathologist. An increase in the number of superficial cells indicates improvement in atrophy.

Outcome measures

Measure	Ospemifene n=306 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=308 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in the Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear at Weeks 4 and 8 Week 4	5.6 percentage of cells Standard Error 0.6	-0.2 percentage of cells Standard Error 0.6
Change From Baseline in the Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear at Weeks 4 and 8 Week 8	7.1 percentage of cells Standard Error 0.7	-0.2 percentage of cells Standard Error 0.6

SECONDARY outcome

Timeframe: Baseline and Weeks 4 and 8

Population: Intent-to-treat population with available baseline data

The pH scale ranges from 0 to 14. A pH of 7 is neutral, less than 7 is acidic, and greater than 7 is basic. A typical vaginal pH in women of reproductive age is between 3.5 and 4.5, increasing to > 4.5 after menopause. Vaginal pH was measured by the investigator using a pH indicator strip at the middle third of the vaginal wall.

Outcome measures

Measure	Ospemifene n=313 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=314 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in the Vaginal pH Week 4	-0.81 pH Standard Error 0.04	-0.24 pH Standard Error 0.04
Change From Baseline in the Vaginal pH Week 8	-0.95 pH Standard Error 0.04	-0.32 pH Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline and Weeks 4 and 8

Population: Intent-to-treat population with available data at baseline

The severity of the most bothersome symptom of vaginal dryness was assessed by the participant through the VVA questionnaire as none = 0, mild = 1, moderate = 2, and severe = 3.

Outcome measures

Measure	Ospemifene n=313 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=314 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in the Severity of Self-reported Most Bothersome Symptom (MBS) of Vaginal Dryness at Weeks 4 and 8 Week 4	-0.83 units on a scale Standard Deviation 0.90	-0.62 units on a scale Standard Deviation 0.89
Change From Baseline in the Severity of Self-reported Most Bothersome Symptom (MBS) of Vaginal Dryness at Weeks 4 and 8 Week 8	-1.14 units on a scale Standard Deviation 0.97	-0.84 units on a scale Standard Deviation 0.95

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, and 12

Population: Intent-to-treat population; participants whose baseline values were moderate or severe were included

The severity of vaginal and/or vulvar irritation or itching was assessed by the participant through the VVA questionnaire as none = 0, mild = 1, moderate = 2, and severe = 3.

Outcome measures

Measure	Ospemifene n=130 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=138 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Vaginal and/or Vulvar Irritation or Itching Week 4	-0.93 units on a scale Standard Deviation 1.00	-0.99 units on a scale Standard Deviation 1.02
Change From Baseline in Vaginal and/or Vulvar Irritation or Itching Week 8	-1.17 units on a scale Standard Deviation 1.01	-1.16 units on a scale Standard Deviation 1.04
Change From Baseline in Vaginal and/or Vulvar Irritation or Itching Week 12	-1.38 units on a scale Standard Deviation 1.00	-1.40 units on a scale Standard Deviation 0.96

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, and 12

Population: Intent-to-treat population; participants whose baseline values were moderate or severe were included.

The severity of difficult or painful urination was assessed by the participant through the VVA questionnaire as none = 0, mild = 1, moderate = 2, and severe = 3.

Outcome measures

Measure	Ospemifene n=40 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=37 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Difficult or Painful Urination Week 4	-1.23 units on a scale Standard Deviation 1.01	-1.21 units on a scale Standard Deviation 0.84
Change From Baseline in Difficult or Painful Urination Week 8	-1.42 units on a scale Standard Deviation 0.95	-1.15 units on a scale Standard Deviation 0.97
Change From Baseline in Difficult or Painful Urination Week 12	-1.56 units on a scale Standard Deviation 0.93	-1.38 units on a scale Standard Deviation 0.91

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, and 12

Population: Intent-to-treat population; participants whose baseline values were moderate or severe were included

The severity of vaginal pain associated with sexual activity was assessed by the participant through the VVA questionnaire as none = 0, mild = 1, moderate = 2, and severe = 3.

Outcome measures

Measure	Ospemifene n=201 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=203 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Vaginal Pain Associated With Sexual Activity Week 4	-1.24 units on a scale Standard Deviation 1.11	-0.99 units on a scale Standard Deviation 1.11
Change From Baseline in Vaginal Pain Associated With Sexual Activity Week 8	-1.41 units on a scale Standard Deviation 1.08	-1.26 units on a scale Standard Deviation 1.13
Change From Baseline in Vaginal Pain Associated With Sexual Activity Week 12	-1.55 units on a scale Standard Deviation 1.05	-1.21 units on a scale Standard Deviation 1.07

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, and 12

Population: Intent-to-treat population; participants whose baseline values were moderate or severe were included

The severity of vaginal bleeding associated with sexual activity was assessed by the participant through the VVA questionnaire as none = 0, mild = 1, moderate = 2, and severe = 3.

Outcome measures

Measure	Ospemifene n=51 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=37 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Vaginal Bleeding Associated With Sexual Activity Week 4	-1.17 units on a scale Standard Deviation 1.09	-1.33 units on a scale Standard Deviation 1.14
Change From Baseline in Vaginal Bleeding Associated With Sexual Activity Week 8	-1.47 units on a scale Standard Deviation 0.92	-1.58 units on a scale Standard Deviation 1.09
Change From Baseline in Vaginal Bleeding Associated With Sexual Activity Week 12	-1.55 units on a scale Standard Deviation 0.79	-1.61 units on a scale Standard Deviation 1.06

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, and 12

Population: Intent-to-treat population with available data at each time point

The maturation value is an indicator of the level of maturation attained by the vaginal epithelium.

Vaginal smear samples were taken from the middle third of the lateral vaginal wall and were evaluated at the central laboratory by a qualified pathologist. Parabasal cells (P), intermediary cells (I), and superficial cells (S) were counted and results were expressed as the maturation value (MV), whereby superficial cells were assigned a point value of 1.0, intermediate cells were assigned a point value of 0.5, and parabasal cells were assigned a point value of 0. The maturation value (MV) was defined as:

(percentage of superficial cells * 1) + (percentage of intermediate cells * 0.5) + (percentage of parabasal calls * 0).

Lower MV indicates lower estrogen effect.

Outcome measures

Measure	Ospemifene n=306 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=308 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Maturation Value Week 4	13.33 units on a scale Standard Error 0.79	-0.65 units on a scale Standard Error 0.75
Change From Baseline in Maturation Value Week 8	15.34 units on a scale Standard Error 0.82	0.61 units on a scale Standard Error 0.78
Change From Baseline in Maturation Value Week 12	16.19 units on a scale Standard Error 0.87	1.28 units on a scale Standard Error 0.83

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, and 12

Population: Intent-to-treat population with available data at each time point

A participant was defined as a responder if all the following conditions were met::

• Increase from baseline in maturation value of at least 10
• Decrease from baseline in vaginal pH of at least 0.5
• Improvement from baseline (decrease in severity) of at least 1 point in the most bothersome symptom of vaginal dryness

Outcome measures

Measure	Ospemifene n=313 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=314 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Percentage of Participants Who Were Responders at Week 4, Week 8, and Week 12 Week 4	19.2 percentage of participants	2.6 percentage of participants
Percentage of Participants Who Were Responders at Week 4, Week 8, and Week 12 Week 8	27.9 percentage of participants	4.4 percentage of participants
Percentage of Participants Who Were Responders at Week 4, Week 8, and Week 12 Week 12	31.5 percentage of participants	6.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, and 12

Population: Intent-to-treat population with available data at each time point

The investigator performed an evaluation of the vagina, assessing overall elasticity, fluid secretion, pH, condition of epithelial mucosa, and moisture. The severity of each characteristic was assessed using a 5-grade scale from 1 (worst) to 5 (best). The total score was calculated as the sum of the 5 individual scores and ranges from 5 to 25, where higher scores indicate better vaginal health

Outcome measures

Measure	Ospemifene n=312 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=312 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Vaginal Health Index Week 4	3.9 units on a scale Standard Error 0.2	1.5 units on a scale Standard Error 0.2
Change From Baseline in Vaginal Health Index Week 8	5.0 units on a scale Standard Error 0.2	2.1 units on a scale Standard Error 0.2
Change From Baseline in Vaginal Health Index Week 12	5.2 units on a scale Standard Error 0.2	2.3 units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, and 12

Population: Intent-to-treat population with available data at each timepoint

The investigator performed a visual examination of the vulva, assessing the labia majora, labia minora, clitoris, introitus appearance and elasticity, color, discomfort and pain, and presence of other findings (eg, petechiae, excoriations, ulcers, etc). The severity of each characteristic was assessed on a 4-point scale as 0 = normal, 1 = mild, 2 = moderate, and 3 = severe. The total score was calculated by adding the 7 individual scores and ranges from 0 to 21, where lower scores indicate better vulvar health. A negative change from baseline indicates improvement.

Outcome measures

Measure	Ospemifene n=308 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=308 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Vulvar Health Index Week 4	-2.2 units on a scale Standard Error 0.2	-1.4 units on a scale Standard Error 0.2
Change From Baseline in Vulvar Health Index Week 8	-2.8 units on a scale Standard Error 0.2	-1.7 units on a scale Standard Error 0.2
Change From Baseline in Vulvar Health Index week 12	-2.8 units on a scale Standard Error 0.2	-1.6 units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population; participants who agreed to participate in the optional vaginal imaging, and with available data at both time points were included.

Vulvovaginal imaging was performed by trained site personnel following a standard procedure. Photographs were assessed by an Independent Panel Review (IPR) in a blinded fashion. Nine parameters (labia majora, labia minora, clitoris, urethra, introitus and elasticity, color, erythema, moisture, and other findings (petechiae, excoriation, ulceration, etc.)) were evaluated on a scale from 0 (normal/none) to 3 (severe). The total score was calculated from the sum of the 9 individual scores and ranged from 0 to 27 with lower values indicating better vulvovaginal health; a negative change from baseline indicates improvement.

Outcome measures

Measure	Ospemifene n=135 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=141 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Vulvovaginal Imaging Total Score at Week 12	-1.1 units on a scale Standard Error 0.3	-0.1 units on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, and 12

Population: Intent-to-treat population with available data at each time point

The Female Sexual Function Index consists of 19 questions organized into 6 domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) answered by the participant on a 5-point scale from 1 to 5. Where relevant, some questions also include an option of 0 if a question is not applicable due to no sexual activity. Each domain score was calculated by adding the scores of each item in the domain and multiplying by a domain factor. The total score was calculated by summing each domain score and ranges from 2 to 36, with higher values indicating better sexual function.

Outcome measures

Measure	Ospemifene n=303 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=308 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Female Sexual Function Index Total Score Week 4	4.13 units on a scale Standard Error 0.43	4.11 units on a scale Standard Error 0.43
Change From Baseline in Female Sexual Function Index Total Score Week 8	4.70 units on a scale Standard Error 0.49	4.51 units on a scale Standard Error 0.49
Change From Baseline in Female Sexual Function Index Total Score Week 12	5.71 units on a scale Standard Error 0.55	4.13 units on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available baseline and Week 12 data

The Female Sexual Function Index consists of 19 questions, organized into 6 domains (desire, arousal, lubrication, orgasm, satisfaction, and pain), answered by the participant on a scale from 1 to 5. Where relevant, some questions also include an option of 0 if not applicable due to no sexual activity. Each domain score was calculated by adding the scores of each item in the domain and multiplying by a domain factor. For all domains, higher values indicate better sexual function, according to the following:

Desire (2 questions): domain score ranges from 1.2 to 6; Arousal (4 questions): domain score ranges from 0 to 6; Lubrication (4 questions): domain score ranges from 0 to 6; Orgasm (3 questions): domain score ranges from 0 to 6; Satisfaction (3 questions): domain score ranges from 0.8 to 6; Pain (3 questions): domain score ranges from 0 to 6.

Outcome measures

Measure	Ospemifene n=303 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=308 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Female Sexual Function Index Domain Scores at Week 12 Desire	0.56 units on a scale Standard Error 0.07	0.39 units on a scale Standard Error 0.06
Change From Baseline in Female Sexual Function Index Domain Scores at Week 12 Arousal	0.64 units on a scale Standard Error 0.11	0.44 units on a scale Standard Error 0.11
Change From Baseline in Female Sexual Function Index Domain Scores at Week 12 Lubrication	1.29 units on a scale Standard Error 0.12	0.89 units on a scale Standard Error 0.12
Change From Baseline in Female Sexual Function Index Domain Scores at Week 12 Orgasm	0.78 units on a scale Standard Error 0.12	0.63 units on a scale Standard Error 0.11
Change From Baseline in Female Sexual Function Index Domain Scores at Week 12 Satisfaction	0.78 units on a scale Standard Error 0.09	0.62 units on a scale Standard Error 0.09
Change From Baseline in Female Sexual Function Index Domain Scores at Week 12 Pain	1.47 units on a scale Standard Error 0.12	1.01 units on a scale Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, and 12

Population: Intent-to-treat population with available data at each time point

The presence or absence of urinary symptoms was assessed using the Urinary Distress Inventory (UDI)-6. The symptoms include frequent urination, urine leakage related to the feeling of urgency, urine leakage related to physical activity, coughing, or sneezing, small amounts of urine leakage, difficulty emptying bladder, and pain and discomfort in the lower abdominal or genital area. If a symptom was present, participants were asked to assess the degree to which they were bothered by it on the following 4-point scale:

1. = present but doesn't bother her at all;

2. = present and bothers her slightly;

3. = present and bothers her moderately;

4. = present and bothers her greatly. The total score was calculated by adding the 6 scores together (Absent = 0), and ranges from 0 to 24, with lower values indicating less urinary distress.

Outcome measures

Measure	Ospemifene n=311 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=314 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Urinary Distress Inventory (UDI)-6 Total Score Week 4	-0.8 units on a scale Standard Error 0.2	-0.9 units on a scale Standard Error 0.2
Change From Baseline in Urinary Distress Inventory (UDI)-6 Total Score Week 8	-1.0 units on a scale Standard Error 0.2	-1.4 units on a scale Standard Error 0.2
Change From Baseline in Urinary Distress Inventory (UDI)-6 Total Score Week 12	-1.3 units on a scale Standard Error 0.2	-1.6 units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Serum bone sialoprotein (BSP) was measured as a marker of bone resorption.

Outcome measures

Measure	Ospemifene n=264 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=271 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Bone Sialoprotein at Week 12	-24964.3 pg/mL Standard Error 3922.5	-20576.1 pg/mL Standard Error 3871.5

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Type I collagen C-telopeptide was measured as a marker of bone resorption.

Outcome measures

Measure	Ospemifene n=261 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=260 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Type I Collagen C-Telopeptide (CTX) at Week 12	-0.044 ng/mL Standard Error 0.008	0.006 ng/mL Standard Error 0.008

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Deoxypyridinoline was measured as a marker of bone resorption.

Outcome measures

Measure	Ospemifene n=261 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=260 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Deoxypyridinoline at Week 12	0.08 µmol/mol creatinine Standard Error 0.16	0.22 µmol/mol creatinine Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Type I collagen N-telopeptide was measured as a marker of bone resorption.

Outcome measures

Measure	Ospemifene n=265 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=270 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Type I Collagen N-Telopeptide (NTX) at Week 12	-0.10 nmol bone collagen equivalents (BCE)/L Standard Error 0.23	0.65 nmol bone collagen equivalents (BCE)/L Standard Error 0.23

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Tartrate-resistant acid phosphatase 5b was measured as a marker of bone resorption.

Outcome measures

Measure	Ospemifene n=265 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=270 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Tartrate-Resistant Acid Phosphatase 5b at Week 12	-0.28 units/L Standard Error 0.04	-0.06 units/L Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Alkaline phosphatase was measured as a marker of bone formation.

Outcome measures

Measure	Ospemifene n=258 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=261 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Alkaline Phosphatase at Week 12	-4.6 units/L Standard Error 0.7	1.6 units/L Standard Error 0.7

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Bone-specific alkaline phosphatase was measured as a marker of bone formation.

Outcome measures

Measure	Ospemifene n=265 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=270 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Bone-specific Alkaline Phosphatase at Week 12	-0.50 units/L Standard Error 0.36	0.84 units/L Standard Error 0.36

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Osteocalcin was measured as a marker for bone formation.

Outcome measures

Measure	Ospemifene n=265 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=270 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Osteocalcin at Week 12	-1.43 ng/mL Standard Error 0.31	0.62 ng/mL Standard Error 0.31

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Procollagen 1 N-terminal propeptide was measured as a marker of bone formation.

Outcome measures

Measure	Ospemifene n=261 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=260 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Procollagen 1 N-Terminal Propeptide (P1NP) at Week 12	-3.22 ng/mL Standard Error 0.85	2.04 ng/mL Standard Error 0.86

SECONDARY outcome

Timeframe: Week 1 to Week 12

Population: Intent-to-treat population with available data

The mean number of days/week that lubricant was used as documented by participants in an electronic daily diary.

Outcome measures

Measure	Ospemifene n=302 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=304 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Mean Days of Lubricant Use Per Week	0.8 days/week Standard Deviation 1.3	0.8 days/week Standard Deviation 1.2

SECONDARY outcome

Timeframe: Week 1 to Week 12

Population: Intent-to-treat population with available data

The mean number of days/week of intercourse as recorded by participants in an electronic daily diary.

Outcome measures

Measure	Ospemifene n=302 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=304 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Mean Days of Intercourse Per Week	0.9 days/week Standard Deviation 1.0	0.9 days/week Standard Deviation 1.1

SECONDARY outcome

Timeframe: Week 12

Population: Intent-to-treat population with available data

Participants were asked to record their overall satisfaction with treatment in an electronic diary according to the following categories: Very satisfied, Moderately satisfied, About equally satisfied and dissatisfied, Moderately dissatisfied, and Very dissatisfied.

Outcome measures

Measure	Ospemifene n=221 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=198 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Overall Satisfaction With Treatment at Week 12 Very satisfied	83 Participants	54 Participants
Overall Satisfaction With Treatment at Week 12 Moderately satisfied	71 Participants	52 Participants
Overall Satisfaction With Treatment at Week 12 About equally satisfied and dissatisfied	43 Participants	49 Participants
Overall Satisfaction With Treatment at Week 12 Moderately dissatisfied	13 Participants	26 Participants
Overall Satisfaction With Treatment at Week 12 Very dissatisfied	11 Participants	17 Participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Outcome measures

Measure	Ospemifene n=266 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=269 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Estradiol at Week 12	-2.5 pg/mL Standard Deviation 19.6	0.5 pg/mL Standard Deviation 10.3

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Outcome measures

Measure	Ospemifene n=268 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=270 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Follicle-Stimulating Hormone at Week 12	-5.18 IU/L Standard Deviation 12.64	-1.96 IU/L Standard Deviation 11.79

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Outcome measures

Measure	Ospemifene n=266 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=270 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Luteinizing Hormone at Week 12	-1.58 IU/L Standard Deviation 8.54	-0.38 IU/L Standard Deviation 7.59

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Outcome measures

Measure	Ospemifene n=262 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=267 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Sex Hormone-Binding Globulin at Week 12	30.44 nmol/L Standard Deviation 31.89	1.73 nmol/L Standard Deviation 17.61

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Outcome measures

Measure	Ospemifene n=262 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=267 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Testosterone at Week 12	1.1 ng/dL Standard Deviation 9.1	1.2 ng/dL Standard Deviation 20.2

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population with available data

Outcome measures

Measure	Ospemifene n=262 Participants Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=267 Participants Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Change From Baseline in Free Testosterone at Week 12	0.0000 nmol/L Standard Deviation 0.0035	0.0007 nmol/L Standard Deviation 0.0115

Adverse Events

Ospemifene

Serious events: 5 serious events

Other events: 37 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ospemifene n=317 participants at risk Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=310 participants at risk Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Infections and infestations Bronchitis	0.32% 1/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	0.00% 0/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.
Psychiatric disorders Depression	0.32% 1/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	0.00% 0/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.
Nervous system disorders Transient global amnesia	0.00% 0/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	0.32% 1/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.
Cardiac disorders Acute myocardial infarction	0.32% 1/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	0.00% 0/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.32% 1/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	0.00% 0/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.32% 1/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	0.00% 0/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.
Gastrointestinal disorders Enterocolitis	0.00% 0/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	0.32% 1/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.
Injury, poisoning and procedural complications Comminuted fracture	0.00% 0/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	0.32% 1/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.
Injury, poisoning and procedural complications Upper limb fracture	0.32% 1/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	0.00% 0/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.

Other adverse events

Measure	Ospemifene n=317 participants at risk Participants received one tablet of ospemifene 60 mg orally, once a day for 12 weeks.	Placebo n=310 participants at risk Participants received one tablet of matching placebo, orally, once a day for 12 weeks.
Infections and infestations Nasopharyngitis	1.3% 4/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	2.6% 8/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.
Infections and infestations Upper respiratory tract infection	2.2% 7/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	3.5% 11/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.
Infections and infestations Urinary tract infection	2.2% 7/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	3.2% 10/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.
Nervous system disorders Headache	1.6% 5/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	2.3% 7/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.
Vascular disorders Hot flush	6.3% 20/317 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.	2.6% 8/310 • From the first dose of study drug up to 14 days after the last dose; 14 weeks Participants who received at least 1 dose of study drug. Four participants randomized to placebo received ospemifene in error and are counted in the ospemifene group for safety assessments. One participant randomized to placebo who enrolled at 2 different sites at the same time was excluded.

Additional Information

Shionogi Clinical Trials Administrator

Shionogi Inc.

Phone: 800-849-9707

Email: shionogiclintrials-admin@shionogi.co.jp

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.
• Publication restrictions are in place

Restriction type: OTHER