A Clinical Study to Evaluate the Efficacy and Safety of Ospemifene in the Treatment of Vulvar and Vaginal Atrophy (VVA) in Postmenopausal Women

• Sponsor: Shionogi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00630539
• Collaborator: Hormos Medical (Industry), QuatRx Pharmaceuticals (Industry)
• Enrollment: 126
• Arms: 4
• Duration (Months): 6

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the efficacy, safety and tolerability of Ospemifene 5 mg, 15 mg, and 30 mg in the treatment of VVA in postmenopausal women to find the minimum effective dose below the lowest dose of 30 mg tested earlier in Phase II.

Condition or Disease	Intervention/Treatment	Phase
Atrophy; Vaginal Diseases	Drug: Placebo; Drug: Ospemifene 5 mg; Drug: Ospemifene 15 mg; Drug: Ospemifene 30 mg	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 126 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Ospemifene in the Treatment of Vulvar and Vaginal Atrophy (VVA) in Postmenopausal Women: A Phase II Dose Ranging, 12-Week, Randomized , Double-Blind, Placebo-Controlled, Parallel-Group Study Comparing Oral Ospemifene 5 mg, 15 mg and 30 mg Daily Doses With Placebo
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Subjects on placebo Subjects will self-administer 1 placebo tablet daily (in the morning with food) for 12 weeks	Drug: Placebo; 1 tablet per day, orally, in the morning, with food for 12 weeks - from Visit 2 (Randomization, Day 1) to Visit 4 (End of therapy, Week 12).
Experimental: Subjects on ospemifene 5 mg/day Subjects will self-administer 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Drug: Ospemifene 5 mg; 1 tablet of ospemifene 5 mg (QD), orally, in the morning, with food for 12 weeks - from Visit 2 (Randomization, Day 1) to Visit 4 (End of therapy, Week 12).
Experimental: Subjects on ospemifene 15 mg/day Subjects will self-administer 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Drug: Ospemifene 15 mg; 1 tablet of ospemifene 15 mg (QD), orally, in the morning, with food for 12 weeks - from Visit 2 (Randomization, Day 1) to Visit 4 (End of therapy, Week 12).
Experimental: Subjects on ospemifene 30 mg/day Subjects will self-administer 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks	Drug: Ospemifene 30 mg; 1 tablet of ospemifene 30 mg (QD), orally, in the morning, with food for 12 weeks - from Visit 2 (Randomization, Day 1) to Visit 4 (End of therapy, Week 12).

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear [12 weeks]

2. Mean Change From Baseline in Percentage of Superficial Cells in Maturation Index of the Vaginal Smear [12 weeks]

3. Mean Change From Baseline in Vaginal pH [12 weeks]

Secondary Outcome Measures

1. Visual Evaluation of Vagina (by Gynecological Examination) [Screening & Week 12]

2. Mean Change From Baseline in Vaginal pH [Week 4]

3. Mean Change From Baseline in Percentage of Superficial Cells in the Maturation Index [Week 4]

4. Mean Change From Baseline in Estradiol Levels [Week 12]

5. Mean Change From Baseline in Luteinizing Hormone Levels [Week 12]

6. Mean Change From Baseline in Follicle Stimulating Hormone Levels [Week 12]

7. Mean Change From Baseline in Sex Hormone Binding Globulin Levels [Week 12]

8. Mean Change From Baseline in Percentage of Parabasal Cells in the Maturation Index [Week 4]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Naturally or surgically menopausal

• 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Shionogi
• Hormos Medical
• QuatRx Pharmaceuticals

Investigators

• Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line, Shionogi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00630539
• Other Study ID Numbers: 15-50717
• First Posted: Mar 7, 2008
• Last Update Posted: Jun 28, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by , ,: Menopausal symptoms; Urogenital atrophy; Vulvar and vaginal atrophy in postmenopausal women; Vaginal atrophy
• Additional relevant MeSH terms: Vaginal Diseases; Atrophy; Tamoxifen

Study Results

Participant Flow

Recruitment Details	The study was conducted at 9 centers in Finland. First patient was enrolled on August 09, 2007 and last patient completed on February 11, 2008
Pre-assignment Detail	The study population included postmenopausal women 40 to 80 years of age with a diagnosis of vulvar and vaginal atrophy (VVA) assessed by the maturation index (MI) of vaginal smear and vaginal pH at baseline

Arm/Group Title	Subjects on Placebo	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifene 30 mg/Day
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
Period Title: Overall Study
STARTED	34	33	29	30
COMPLETED	33	29	28	27
NOT COMPLETED	1	4	1	3

Baseline Characteristics

Arm/Group Title	Subjects on Placebo	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifene 30 mg/Day	Total
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks	Total of all reporting groups
Overall Participants	34	33	29	30	126
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.8 (6.0)	61.5 (5.6)	63.4 (7.1)	62.0 (6.8)	62.4 (6.4)
Sex: Female, Male (Count of Participants)
Female	34 100%	33 100%	29 100%	30 100%	126 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Participants	34 100%	33 100%	29 100%	30 100%	126 100%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	69.6 (10.1)	66.5 (10.6)	68.7 (13.5)	65.9 (7.4)	67.7 (10.4)
Height (m) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m]	1.609 (0.049)	1.636 (.051)	1.641 (.062)	1.617 (.058)	1.626 (0.055)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.89 (3.95)	24.78 (3.44)	25.50 (4.99)	25.28 (3.20)	25.61 (3.90)
Alcohol (drinks/week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [drinks/week]	0.9 (1.9)	1.8 (2.4)	1.2 (1.7)	1.5 (2.3)	1.4 (2.1)

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Subjects on Placebo	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifene 30 mg/Day
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
Measure Participants	34	33	29	30
Mean (Standard Deviation) [percentage of parabasal cells]	-3.0 (30.2)	-2.8 (33.2)	-24.1 (36.7)	-26.8 (41.1)

2. Primary Outcome

Title	Mean Change From Baseline in Percentage of Superficial Cells in Maturation Index of the Vaginal Smear
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Subjects on Placebo	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifene 30 mg/Day
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
Measure Participants	34	33	29	30
Mean (Standard Deviation) [percentage of superficial cells]	0.2 (1.5)	0.9 (3.1)	5.0 (9.1)	5.6 (10.3)

3. Primary Outcome

Title	Mean Change From Baseline in Vaginal pH
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Subjects on Placebo	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifene 30 mg/Day
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
Measure Participants	34	33	29	30
Mean (Standard Deviation) [pH]	-0.07 (0.91)	-0.37 (0.83)	-0.95 (1.02)	-1.11 (1.06)

4. Secondary Outcome

Title	Visual Evaluation of Vagina (by Gynecological Examination)
Time Frame	Screening & Week 12

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Subjects on Placebo	Subjects on Placebo (Week 12)	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 5 mg/Day (Week 12)	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifine 15 mg/Day (Week 12)	Subjects on Ospemifene 30 mg/Day	Subjects on Ospemifene 30 mg/Day (Week 12)
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
Measure Participants	34	34	33	33	29	29	30	30
Petechiae-None	14.7	35.3	24.2	36.4	10.3	55.2	10.0	60.0
Petechiae-Mild	47.1	29.4	42.4	39.4	55.2	24.1	53.3	30.0
Petechiae-Moderate	26.5	26.5	12.1	6.1	31.0	17.2	26.7	3.3
Petechiae-Severe	11.8	8.8	21.2	15.2	3.4	0.0	10.0	3.3
Petechiae-Not done	0.0	0.0	0.0	3.0	0.0	3.4	0.0	0.0
Pallor-None	8.8	14.7	6.1	15.2	13.8	37.9	6.7	46.7
Pallor-Mild	44.1	47.1	30.3	48.5	48.3	48.3	40.0	43.3
Pallor-Moderate	41.2	35.3	57.6	30.3	31.0	10.3	43.3	6.7
Pallor-Severe	5.9	2.9	6.1	3.0	6.9	0.0	10.0	0.0
Pallor-Not done	0.0	0.0	0.0	3.0	0.0	3.4	0.0	0.0
Friability-None	8.8	20.6	15.2	30.3	10.3	44.8	16.7	60.0
Friability-Mild	41.2	32.4	27.3	30.3	34.5	44.8	40.0	33.3
Friability-Moderate	38.2	41.2	36.4	33.3	48.3	6.9	23.3	3.3
Friability-Severe	11.8	5.9	21.2	3.0	6.9	0.0	20.0	0.0
Friability-Not done	0.0	0.0	0.0	3.0	0.0	3.4	0.0	0.0
Vaginal dryness in the mucosa-None	8.8	23.5	6.1	27.3	10.3	51.7	10.0	73.3
Vaginal dryness in the mucosa-Mild	47.1	41.2	21.2	36.4	41.4	37.9	43.3	16.7
Vaginal dryness in the mucosa-Moderate	38.2	32.4	63.6	30.3	37.9	6.9	33.3	6.7
Vaginal dryness in the mucosa-Severe	5.9	2.9	9.1	3.0	10.3	0.0	13.3	0.0
Vaginal dryness in the mucosa-Not done	0.0	0.0	0.0	3.0	0.0	3.4	0.0	0.0
Vaginal redness in the mucosa-None	8.8	20.6	18.2	39.4	17.2	51.7	10.0	53.3
Vaginal redness in the mucosa-Mild	52.9	41.2	33.3	21.2	48.3	27.6	50.0	40.0
Vaginal redness in the mucosa-Moderate	26.5	26.5	33.3	21.2	31.0	17.2	23.3	0.0
Vaginal redness in the mucosa-Severe	11.8	11.8	15.2	15.2	3.4	0.0	16.7	3.3
Vaginal redness in the mucosa-Not done	0.0	0.0	0.0	3.0	0.0	3.4	0.0	0.0

5. Secondary Outcome

Title	Mean Change From Baseline in Vaginal pH
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Subjects on Placebo	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifene 30 mg/Day
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
Measure Participants	34	33	29	30
Mean (Standard Deviation) [pH]	-0.12 (0.59)	-0.26 (0.68)	-0.53 (0.83)	-0.78 (1.00)

6. Secondary Outcome

Title	Mean Change From Baseline in Percentage of Superficial Cells in the Maturation Index
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Subjects on Placebo	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifene 30 mg/Day
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
Measure Participants	34	33	29	30
Mean (Standard Deviation) [percentage of superficial cells]	0.6 (2.7)	0.6 (2.9)	2.5 (5.6)	5.0 (10.7)

7. Secondary Outcome

Title	Mean Change From Baseline in Estradiol Levels
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Subjects on Placebo	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifene 30 mg/Day
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
Measure Participants	34	33	29	30
Mean (Standard Deviation) [nmol/L]	-0.004 (0.011)	0.004 (0.015)	-0.010 (0.026)	-0.003 (0.008)

8. Secondary Outcome

Title	Mean Change From Baseline in Luteinizing Hormone Levels
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Subjects on Placebo	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifene 30 mg/Day
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
Measure Participants	34	33	29	30
Mean (Standard Deviation) [U/L]	-1.36 (4.71)	-2.89 (5.94)	-0.34 (9.23)	-3.78 (7.34)

9. Secondary Outcome

Title	Mean Change From Baseline in Follicle Stimulating Hormone Levels
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Subjects on Placebo	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifene 30 mg/Day
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
Measure Participants	34	33	29	30
Mean (Standard Deviation) [U/L]	-10.36 (20.41)	-7.04 (10.80)	-5.99 (23.07)	-15.32 (13.13)

10. Secondary Outcome

Title	Mean Change From Baseline in Sex Hormone Binding Globulin Levels
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Subjects on Placebo	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifene 30 mg/Day
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
Measure Participants	34	33	29	30
Mean (Standard Deviation) [nmol/L]	-2.4 (10.0)	2.9 (12.2)	6.3 (12.5)	18.0 (20.2)

11. Secondary Outcome

Title	Mean Change From Baseline in Percentage of Parabasal Cells in the Maturation Index
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Subjects on Placebo	Subjects on Ospemifene 5 mg/Day	Subjects on Ospemifene 15 mg/Day	Subjects on Ospemifene 30 mg/Day
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks	Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
Measure Participants	34	33	29	30
Mean (Standard Deviation) [percentage of parabasal cells]	-0.6 (24.1)	-0.6 (23.8)	-19.7 (27.0)	-22.0 (42.7)

Adverse Events

Time Frame	Throughout the study
Arm/Group Title	Subjects on Placebo		Subjects on Ospemifene 5 mg/Day		Subjects on Ospemifene 15 mg/Day		Subjects on Ospemifene 30 mg/Day
Arm/Group Description	Subjects took 1 placebo tablet daily (in the morning with food) for 12 weeks		Subjects took 1 ospemifene 5 mg tablet daily (in the morning with food) for 12 weeks		Subjects took 1 ospemifene 15 mg tablet daily (in the morning with food) for 12 weeks		Subjects took 1 ospemifene 30 mg tablet daily (in the morning with food) for 12 weeks
All Cause Mortality
	Subjects on Placebo		Subjects on Ospemifene 5 mg/Day		Subjects on Ospemifene 15 mg/Day		Subjects on Ospemifene 30 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Subjects on Placebo		Subjects on Ospemifene 5 mg/Day		Subjects on Ospemifene 15 mg/Day		Subjects on Ospemifene 30 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/34 (2.9%)		0/33 (0%)		0/29 (0%)		0/30 (0%)
Injury, poisoning and procedural complications
Ankle fracture	1/34 (2.9%)		0/33 (0%)		0/29 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Subjects on Placebo		Subjects on Ospemifene 5 mg/Day		Subjects on Ospemifene 15 mg/Day		Subjects on Ospemifene 30 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/34 (73.5%)		7/33 (21.2%)		13/29 (44.8%)		16/30 (53.3%)
Infections and infestations
Influenza	2/34 (5.9%)		0/33 (0%)		1/29 (3.4%)		2/30 (6.7%)
Respiratory tract infection	2/34 (5.9%)		0/33 (0%)		0/29 (0%)		0/30 (0%)
Urinary tract infection	2/34 (5.9%)		1/33 (3%)		0/29 (0%)		2/30 (6.7%)
Vaginitis bacterial	2/34 (5.9%)		0/33 (0%)		0/29 (0%)		0/30 (0%)
Musculoskeletal and connective tissue disorders
Back pain	2/34 (5.9%)		2/33 (6.1%)		0/29 (0%)		1/30 (3.3%)
Muscle spasms	1/34 (2.9%)		0/33 (0%)		0/29 (0%)		2/30 (6.7%)
Pain in jaw	2/34 (5.9%)		0/33 (0%)		0/29 (0%)		0/30 (0%)
Nervous system disorders
Dizziness	2/34 (5.9%)		0/33 (0%)		0/29 (0%)		2/30 (6.7%)
Headache	1/34 (2.9%)		1/33 (3%)		5/29 (17.2%)		1/30 (3.3%)
Psychiatric disorders
Insomnia	2/34 (5.9%)		0/33 (0%)		1/29 (3.4%)		0/30 (0%)
Renal and urinary disorders
Dysuria	2/34 (5.9%)		0/33 (0%)		0/29 (0%)		0/30 (0%)
Reproductive system and breast disorders
Genital discharge	1/34 (2.9%)		0/33 (0%)		2/29 (6.9%)		1/30 (3.3%)
Postmenopausal haemorrhage	0/34 (0%)		0/33 (0%)		0/29 (0%)		2/30 (6.7%)
Vulvovaginal discomfort	2/34 (5.9%)		0/33 (0%)		1/29 (3.4%)		0/30 (0%)
Vascular disorders
Hot flush	2/34 (5.9%)		3/33 (9.1%)		3/29 (10.3%)		3/30 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.