Study Evaluating the Efficacy and Safety of Three Formula... | NCT02967510

ID	Type	Description	Link
2015-005787-42	EudraCT Number

Description Module

Brief Summary

A Phase 2, Dose-ranging, 12-week Randomized, Double-blind, Placebo controlled, Parallel-group Study Evaluating the Efficacy and Safety of Three Formulations of Ultra-low Dose Estriol Vaginal Gel (0.005% Estriol Vaginal Gel, 0.002% Estriol Vaginal Gel, 0.0008% Estriol Vaginal Gel) for the Treatment of Vaginal Dryness in Postmenopausal Women with Vulvovaginal Atrophy.

Vulvovaginal atrophy is a natural consequence of the progressive estrogen deficiency that occurs in menopause. Epidemiological data have indicated that about 50% of otherwise healthy women over 60 years of age experience symptoms related to urogenital atrophy such as vaginal dryness, dyspareunia, burning, itching, as well as urinary complaints or infections of the lower urinary tract. As these alterations frequently affect the quality of life of postmenopausal women, it is important for doctors to detect their presence and offer treatment options. Estrogen therapy is the most effective treatment of moderate to severe symptoms of vulvar and vaginal atrophy. One advantage of local treatment with estrogen is avoidance of first-pass liver metabolism, making it possible to use lower doses of estrogen compared with oral therapy; the local route also minimize systemic adverse effects. The search for therapeutic alternatives which may present improvements in relation to the current products has been encouraged.

Label	Type	Description	Intervention Names
0.005% estriol vaginal gel	Experimental	Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration	Drug: Estriol
0.002% estriol vaginal gel	Experimental	Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration	Drug: Estriol
0.0008% estriol vaginal gel	Experimental	Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration	Drug: Estriol
estriol vaginal gel	Placebo Comparator	Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Estriol	Drug		0.0008% estriol vaginal gel 0.002% estriol vaginal gel 0.005% estriol vaginal gel
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 12 in the Severity of Vaginal Dryness	Percentage of Subjects with change from baseline to week 12 in the severity of vaginal dryness was reported. Severity was defined as: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.	From baseline to week 12
Change From Baseline to Week 12 in Vaginal pH	Change from Baseline to Week 12 in Vaginal pH was reported. A decrease in pH compare to Baseline represents a positive outcome.	Baseline to Week 12
Change From Baseline to Week 12 in the Proportion of Superficial Cells of the Vaginal Epithelium.	Change from Baseline to week 12 in the proportion of superficial cells of the vaginal epithelium was reported.	Baseline to Week 12
Change From Baseline to Week 12 in the Proportion of Parabasal Cells of the Vaginal Epithelium.	Change from Baseline to Week 12 in the proportion of parabasal cells of the vaginal epithelium was reported. A decrease in proportion of parabasal cells compared to Baseline represents a positive outcome.	Baseline to Week 12

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 12 in the Severity of Dyspareunia	Percentage of subjects with change from baseline to week 12 in the severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with the protocol procedures and assessments
Age >40 and <80 years
Postmenopausal (≥12 months since last spontaneous menstrual period, or having 6 months of spontaneous amenorrhea with serum FSH levels >40 IU/L, or ≥6 weeks since bilateral oophorectomy with or without hysterectomy)
BMI ≤36 kg/m2
Vaginal Maturation Index ≤ 5% superficial cells on a vaginal smear
Vaginal pH >5
Moderate to severe vaginal dryness currently reported as the most bothersome symptom of vaginal atrophy.
Documented negative mammogram within 9 months prior to randomization, with normal breast examination at screening.
Negative Papanicolau test at screening (in women with cervix).

Exclusion Criteria:

Subjects with contraindications for hormone therapy with estrogens such as those diagnosed or history of: malignant and premalignant lesions of the breast and/or endometrium, malignancy of the colon, malignant melanoma, hepatic tumor, venous thromboembolic conditions (including deep vein thrombosis or pulmonary embolism), arterial thromboembolic conditions (including angina pectoris, myocardial infarction, or cerebrovascular accident), coagulopathies, vaginal bleeding of unknown etiology, acute liver disease or a history of liver disease as long as liver function tests have failed to return to normal, or porphyria.
Subjects who have abnormal laboratory values at screening that the investigator considers clinically relevant for the purposes of the study.
Subjects with any medical-surgical pathology which is not controlled at the time of inclusion in the study
Subjects with any acute or chronic condition whose management or progression may interfere with the subject´s participation in the study.
Subject with uncontrolled hypertension (>140 mmHg systolic blood pressure and/or ≥90 mmHg diastolic blood pressure).
Subjects with Grade II or higher utero-vaginal prolapse.
Subjects with uterine polyps.
Subjects with symptomatic and/or large uterine fibroids (>3 cm) and/or palpable fibroids at gynecological examination.
Subjects who have had urogenital surgery within 3 months of baseline visit.
Subjects with signs and symptoms suggestive of infection of the genital or urinary tract requiring treatment at the start of the study.
In women who have a uterus, evidence of hyperplasia, cancer or other endometrial pathology in endometrial biopsy.
Subjects who have received the following treatments within the specified time periods prior to screening procedures: any type of non-hormonal vulvovaginal treatment in the 7 days (including cosmetics expected to have an impact on vaginal pH such as special feminine wash gels); phytoestrogens by any route within 1 month; vaginal hormone therapy within 1 month; hormone therapy (estrogen alone, progestin alone or estrogen/progestin combination) by oral, intrauterine or transdermal route within 2 months; progestational implants, estrogen, or estrogen/progestational injectable within 3 months; estrogen pellet therapy or progestin injectable drug therapy within 6 months; percutaneous estrogen lotions or gels within 1 month; testosterone or testosterone derivatives, DHEA, tibolone, or SERMs by any route within 2 months;
Subjects receiving antiepileptic drugs (barbiturates, hydantoins, carbamazepine), certain antibiotics and other antiinfective medicinal products; phenylbutazone; preparations based on medicinal plants that contain St. John's Wort.
Subjects who are allergic to any of the components of the medication under study.
Subjects who are currently participating or have participated in the experimental evaluation of any product within 8 weeks of the start of the study

Facility	Status	City	State	ZIP	Country	Contacts
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U		Brno		602 00	Czechia

ID	Title	Description
FG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
FG001	Estriol 0.002%

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Jun 22, 2017	May 10, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline to Week 12 in the Severity of Vaginal Dryness

Percentage of Subjects with change from baseline to week 12 in the severity of vaginal dryness was reported. Severity was defined as: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

From baseline to week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG003	Placebo	Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Units	Counts
Participants	OG00070 OG00168 OG00270 OG003

Title

Denominators

Categories

Change from Baseline: -3

Title	Measurements
	OG00015 OG00113 OG00213 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG003		Wilcoxon rank-sum test		=0.304	Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians	Median Difference (Final Values)	0			2-Sided	95	-1	0			Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval		Superiority

Primary

Change From Baseline to Week 12 in Vaginal pH

Change from Baseline to Week 12 in Vaginal pH was reported. A decrease in pH compare to Baseline represents a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Least Squares Mean

Standard Error

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG003

Primary

Change From Baseline to Week 12 in the Proportion of Superficial Cells of the Vaginal Epithelium.

Change from Baseline to week 12 in the proportion of superficial cells of the vaginal epithelium was reported.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Least Squares Mean

Standard Error

ratio

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Primary

Change From Baseline to Week 12 in the Proportion of Parabasal Cells of the Vaginal Epithelium.

Change from Baseline to Week 12 in the proportion of parabasal cells of the vaginal epithelium was reported. A decrease in proportion of parabasal cells compared to Baseline represents a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Least Squares Mean

Standard Error

ratio

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 12 in the Severity of Dyspareunia

Percentage of subjects with change from baseline to week 12 in the severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 12 in the Severity of Pruritus or Itching

Percentage of subjects with cvhange from Baseline to Week 12 in the severity of pruritus or itching was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 12 in the Severity of Burning

Percentage of subjects with change from Baseline to Week 12 in the severity of burning was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 12 in the Severity of Dysuria

Percentage of subjects with change from Baseline to Week 12 in the severity of dysuria was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive putcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 12 in the Global Symptom Score 1

Global Symptom Score 1 was defined as the sum of all 5 individual symptom scores at a given visit, and was calculated only when all 5 symptom scores had a response available. the Global Symptom Score 1 ranged at Screening/Baseline between 2 (at least moderate vaginal dryness -per inclusion criteria) to 15 (all 5 studied symptoms severe in intensity). At Week 12/ET visit, the Global Symptom Score ranged between 0 (no symptoms) and 15 (all symptoms severe in intensity). A decrease in score compared to Baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%

Secondary

Change From Baseline to Week 12 in the Global Symptom Score 2

Change from Baseline to Week 12 in the Global Symptom Score 2 was reported. Global Symptom Score 2 was defined as the sum of all 4 individual symptoms excluding dyspareunia (vaginal dryness, pruritus or itching, burning, and dysuria) for each subject at each time point: Screening/Baseline, Week 3 and Week 12/ET., and was calculated only when all 4 symptom scores had a response available. The maximum score possible to be obtained at a visit with the Global Symptom Score 2 was 12 (all symptoms severe in intensity). A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002

Secondary

Change From Baseline to Week 12 in the Severity of Pallor.

Percentage of subjects with change from Baseline to Week 12 in the severity of pallor was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive putcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 12 in the Severity of Friability

Percentage of subjects with change from Baseline to Week 12 in the severity of friability was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 12 in the Severity of Thinning or Flattening of Folds

Percentage of subjects with change from Baseline to Week 12 in the severity of thinning or flattening of folds was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 12 in the Severity of Petechiae

Percentage of subjects with change from Baseline to Week 12 in the severity of presence of petechiae was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 12 in the Severity of Dry Mucosa

Percentage of subjects with change from Baseline to Week 12 in the severity of dry mucosa was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 12

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 3 in the Severity of Vaginal Dryness

Percentage of subjects with change from Baseline to Week 3 in the severity of vaginal dryness was reported. Severity was defined as: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 3 in the Severity of Dyspareunia

Percentage of subjects with change from Baseline to Week 3 in severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint

Posted

Count of Participants

Participants

From baseline to week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 3 in the Severity of Pruritus or Itching

Percentage of subjects with change from Baseline to Week 3 in the severity of pruritus or itching was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 3 in the Severity of Burning

Percentage of subjects with change from Baseline to Week 3 in severity of burning was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 3 in the Severity of Dysuria

Percentage of subjects with change from Baseline to Week 3 in severity of dysuria was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 3 in the Global Symptom Score 1

Global Symptom Score 1 was defined as the sum of all 5 individual symptom scores at a given visit, and was calculated only when all 5 symptom scores had a response available. the Global Symptom Score 1 ranged at Screening/Baseline between 2 (at least moderate vaginal dryness -per inclusion criteria) to 15 (all 5 studied symptoms severe in intensity). At Week 3 visit, the Global Symptom Score ranged between 0 (no symptoms) and 15 (all symptoms severe in intensity). A decrease in score compared to Baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%

Secondary

Change From Baseline to Week 3 in the Global Symptom Score 2

Change from Baseline to Week 3 in the Global Symptom Score 2 was reported. Global Symptom Score 2 was defined as the sum of all 4 individual symptoms excluding dyspareunia (vaginal dryness, pruritus or itching, burning, and dysuria) for each subject at each time point: Screening/Baseline, Week 3 and Week 12/ET., and was calculated only when all 4 symptom scores had a response available. The maximum score possible to be obtained at a visit with the Global Symptom Score 2 was 12 (all symptoms severe in intensity). A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002

Secondary

Change From Baseline to Week 3 in the Severity of Pallor

Percentage of subjects with change from Baseline to Week 3 in severity of pallor was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 3 in the Severity of Friability

Percentage of subjects with change from Baseline to Week 3 in severity of friability was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 3 in the Severity of Thinning or Flattening of Folds

Percentage of subjects with change from Baseline to Week 3 in severity of thinning or flattening of folds was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 3 in the Severity of Presence of Petechiae

Percentage of subjects with change from Baseline to Week 3 in the severity of presence of petechiae was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 3 in the Severity of Dry Mucosa

Percentage of subjects with change from Baseline to Week 3 in severity of dry mucosa was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Count of Participants

Participants

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 3 in Vaginal pH

Change from Baseline to Week 3 in vaginal pH was reported. A decrease in pH compared to Baseline represents a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Least Squares Mean

Standard Error

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG003

Secondary

Change From Baseline to Week 3 in the Proportion of Superficial Cells of the Vaginal Epithelium

Change from baseline to week 3 in the proportion of superficial cells of the vaginal epithelium was reported.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Least Squares Mean

Standard Error

ratio

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Secondary

Change From Baseline to Week 3 in the Proportion of Parabasal Cells of the Vaginal Epithelium

Change from Baseline to Week 3 in the proportion of parabasal cells of the vaginal epithelium was reported. A decrease in proportion of parabasal cells compared to baseline represents a positive outcome.

The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Posted

Least Squares Mean

Standard Error

ratio

Baseline to Week 3

ID	Title	Description
OG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
OG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Flushing	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0021 events1 affected72 at risk EG0030 events0 affected71 at risk
Hypertension	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0021 events1 affected72 at risk EG003
Breast inflammation	Reproductive system and breast disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Vulvovaginal burning sensation	Reproductive system and breast disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Vulvovaginal pruritus	Reproductive system and breast disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0005 events4 affected70 at risk EG0014 events3 affected69 at risk EG0024 events4 affected72 at risk EG003
Animal bite	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Neck injury	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Radius fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected69 at risk EG0020 events0 affected72 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected69 at risk EG0020 events0 affected72 at risk EG003
Blood glucose increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected69 at risk EG0020 events0 affected72 at risk EG003
Hyperchlorhydria	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Loose tooth	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Leukocyturia	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0021 events1 affected72 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected69 at risk EG0020 events0 affected72 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected69 at risk EG0020 events0 affected72 at risk EG003
Arthritis reactive	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected69 at risk EG0020 events0 affected72 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Bacterial vaginosis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0021 events1 affected72 at risk EG003
Bronchitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0021 events1 affected72 at risk EG003
Cystitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected69 at risk EG0023 events2 affected72 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Influenza	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected69 at risk EG0022 events1 affected72 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected70 at risk EG0012 events2 affected69 at risk EG0023 events3 affected72 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0021 events1 affected72 at risk EG003
Sinusitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0021 events1 affected72 at risk EG003
Tooth abscess	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0021 events1 affected72 at risk EG003
Viral infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Vulval abscess	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003

ID	Term
D004963	Estrenes
D004962	Estranes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D045166	Estradiol Congeners
D012739	Gonadal Steroid Hormones
D042341	Gonadal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists

ID	Title	Description
BG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
BG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
BG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
BG003	Placebo	Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Estriol 0.005%	Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12	70	0	70	14	70
EG001	Estriol 0.002%	Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12	69	0	69	11	69
EG002	Estriol 0.0008%	Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12	72	0	72	15	72
EG003	Placebo	Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12	71	3	71	20	71

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Non-Hodgkin´s lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	The event started 7 months after the subject completed the study	EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG0031 events1 affected71 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 19.0	Systematic Assessment		EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003
Pneumonia	Infections and infestations	MedDRA 19.0	Systematic Assessment		EG0000 events0 affected70 at risk EG0010 events0 affected69 at risk EG0020 events0 affected72 at risk EG003