Trial Outcomes & Findings for A Clinical Trial to Assess the Safety of 0.005 % Estriol Vaginal Gel in Hormone Receptor-Positive Postmenopausal Women With Early Stage Breast Cancer in Treatment With Aromatase Inhibitor in the Adjuvant Setting (NCT NCT02413008)

NCT ID: NCT02413008

Last Updated: 2019-08-05

Results Overview

Change from Baseline (mean screening-baseline) to Week 12 in Serum Levels of Follicle Stimulating Hormone (FSH) compare to natural physiological variability (screening-baseline variation)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 61 participants
• Primary outcome timeframe: from baseline to 12 weeks of treatment
• Results posted on: 2019-08-05

Participant Flow

The study had an initial safety phase of the trial started on March 30th, 2015; the treatment phase of the trial started in October 16th, 2015 and the study ended globally on February 10th, 2017

After Inform Consent signature and prior randomization the following data was collected for subject's eligibility: Medical and surgical history and demographics; physical examination, ECOG PS, hematology, blood chemistry, urine test, transvaginal ultrasound, Blood (serum) samples for FSH and LH determination and evaluation of vaginal dryness.

Participant milestones

Measure	0.005% Estriol Vaginal Gel Route: 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	Placebo Vaginal Gel Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Overall Study STARTED	50	11
Overall Study COMPLETED	43	9
Overall Study NOT COMPLETED	7	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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 estriol	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo	Total n=61 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=50 Participants	0 Participants n=11 Participants	0 Participants n=61 Participants
Age, Categorical Between 18 and 65 years	46 Participants n=50 Participants	9 Participants n=11 Participants	55 Participants n=61 Participants
Age, Categorical >=65 years	4 Participants n=50 Participants	2 Participants n=11 Participants	6 Participants n=61 Participants
Age, Continuous	58.9 years STANDARD_DEVIATION 7.6 • n=50 Participants	61.4 years STANDARD_DEVIATION 4.7 • n=11 Participants	59.3 years STANDARD_DEVIATION 7.1 • n=61 Participants
Sex/Gender, Customized Female	50 Participants n=50 Participants	11 Participants n=11 Participants	61 Participants n=61 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Sweden	17 participants n=50 Participants	4 participants n=11 Participants	21 participants n=61 Participants
Region of Enrollment Spain	33 participants n=50 Participants	7 participants n=11 Participants	40 participants n=61 Participants

PRIMARY outcome

Timeframe: from baseline to 12 weeks of treatment

Population: postmenopausal participants

Change from Baseline (mean screening-baseline) to Week 12 in Serum Levels of Follicle Stimulating Hormone (FSH) compare to natural physiological variability (screening-baseline variation)

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Variation in Serum Levels of Follicle Stimulating Hormone (FSH)	-2.8 mIU/ml Interval -13.1 to 7.4	1.4 mIU/ml Interval -5.4 to 15.7

SECONDARY outcome

Timeframe: Change from baseline to week 1, week 3 and week 8

Population: postmenopausal women

Change from Baseline (mean screening-baseline) to Week 1, Week 3 and Week 8 in Serum Levels of Follicle Stimulating Hormone (FSH) compare to natural physiological variability ( screening-baseline variation)

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Variation in Serum Levels of FSH at Week 1, Week 3 and Week 8 change from baseline to week 1	-4.8 mIU/ml Interval -11.6 to 2.6	4.2 mIU/ml Interval -7.8 to 7.3
Variation in Serum Levels of FSH at Week 1, Week 3 and Week 8 change from baseline to week 3	-4.2 mIU/ml Interval -12.0 to 3.5	-0.9 mIU/ml Interval -4.0 to 2.3
Variation in Serum Levels of FSH at Week 1, Week 3 and Week 8 change from baseline to week 8	-2.6 mIU/ml Interval -10.1 to 7.9	5.2 mIU/ml Interval -11.8 to 9.0

SECONDARY outcome

Timeframe: Change from baseline to week 1, week 3, week 8 and week 12

Population: postmenopausal women

Change from (mean screening-baseline) in plasma levels of LH to Week 1, Week 3, Week 8 and Week 12 in Serum Levels of LH compare to natural physiological variability ( screening-baseline variation)

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Variation in Serum Levels of Luteinizing Hormone (LH) change from LH baseline to week 1	-0.6 mIU/ml Interval -3.7 to 2.8	0.2 mIU/ml Interval -1.8 to 8.1
Variation in Serum Levels of Luteinizing Hormone (LH) change from LH baseline to week 3	-0.5 mIU/ml Interval -4.1 to 3.5	0.3 mIU/ml Interval -1.8 to 7.7
Variation in Serum Levels of Luteinizing Hormone (LH) change from LH baseline to week 8	-0.3 mIU/ml Interval -4.9 to 3.1	-1.3 mIU/ml Interval -2.0 to 6.0
Variation in Serum Levels of Luteinizing Hormone (LH) change from LH baseline to week 12	-0.8 mIU/ml Interval -5.3 to 2.9	1.3 mIU/ml Interval -1.6 to 7.1

SECONDARY outcome

Timeframe: Change from baseline to week 1, week 3, week 8 and week 12

Population: postmenopausal women

Change in plasma levels of estriol at weeks 1, 3, 8 and 12 compared to baseline

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Variation in Plasma Levels of Estriol Change between baseline and week 1	-1.7 pg/mL Interval -10.7 to 0.0	0.0 pg/mL Interval 0.0 to 0.0
Variation in Plasma Levels of Estriol Change between baseline and week 3	0.0 pg/mL Interval -3.4 to 0.5	0.0 pg/mL Interval 0.0 to 0.0
Variation in Plasma Levels of Estriol Change between baseline and week 8	0.0 pg/mL Interval -5.0 to 0.5	0.0 pg/mL Interval 0.0 to 0.0
Variation in Plasma Levels of Estriol Change between baseline and week 12	0.0 pg/mL Interval -6.8 to 0.5	0.0 pg/mL Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Change from baseline to week 1, week 3, week 8 and week 12

Population: postmenopausal women

Change in plasma levels of estradiol at weeks 1, 3, 8 and 12 compared to baseline.

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Variation in Plasma Levels of Estradiol Change between baseline and week 1	0.0 pg/mL Interval 0.0 to 0.0	0.0 pg/mL Interval 0.0 to 0.0
Variation in Plasma Levels of Estradiol Change between baseline and week 3	0.0 pg/mL Interval 0.0 to 0.0	0.0 pg/mL Interval 0.0 to 0.0
Variation in Plasma Levels of Estradiol Change between baseline and week 8	0.0 pg/mL Interval 0.0 to 0.0	0.0 pg/mL Interval 0.0 to 0.0
Variation in Plasma Levels of Estradiol Change between baseline and week 12	0.0 pg/mL Interval 0.0 to 0.0	0.0 pg/mL Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Change from baseline to week 1, week 3, week 8 and week 12

Population: postmenopausal women

Change in plasma levels of estrona at weeks 1, 3, 8 and 12 compared to baseline.

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Variation in Plasma Levels of Estrona Change from baseline to week 1	0.0 pg/mL Interval 0.0 to 0.0	0.0 pg/mL Interval 0.0 to 0.0
Variation in Plasma Levels of Estrona Change between baseline and week 3	0.0 pg/mL Interval 0.0 to 0.0	0.0 pg/mL Interval 0.0 to 0.0
Variation in Plasma Levels of Estrona change from baseline to week 8	0.0 pg/mL Interval 0.0 to 0.0	0.0 pg/mL Interval 0.0 to 0.0
Variation in Plasma Levels of Estrona Change from baseline to week 12	0.0 pg/mL Interval 0.0 to 0.0	0.0 pg/mL Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: week 3 and week 12 vs baseline

Population: postmenopausal women

Measurement of vaginal pH on the vaginal secretion using a reactive strip and compare pH value between baseline and the diferent timepoints

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Changes in Vaginal pH Between Baseline and Week 3 and Week 12 Change from baseline to Week 3	2.0 units on a scale Interval 0.5 to 2.5	0.5 units on a scale Interval -0.5 to 1.0
Changes in Vaginal pH Between Baseline and Week 3 and Week 12 Change from baseline to Week 12	1.3 units on a scale Interval 0.5 to 2.5	0.5 units on a scale Interval 0.0 to 1.5

SECONDARY outcome

Timeframe: week 3 and week 12 vs baseline

Population: postmenopausal women

Changes in dyspareunia from baseline to week 3 and week 12 Each symptom will be scored in a numeric scale from 0 to 3, as shown 0 Absence. The symptom is not present

1. The symptom is of mild intensity, without interfering in the patient's activity

2. The symptom is of moderate intensity, causing obvious discomfort to the patient

3. The symptom is stated as very irritating and severe in intensity

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Changes in Dyspareunia Change between baseline and week 3	1.0 score on a scale Interval 1.0 to 2.0	1.0 score on a scale Interval 0.0 to 1.0
Changes in Dyspareunia Change between baseline and week 12	2.0 score on a scale Interval 1.0 to 2.5	1.0 score on a scale Interval 0.0 to 2.0

SECONDARY outcome

Timeframe: Change from baseline to week 3 and week 12

Population: postmenopausal women

Change in pruritus or itching from baseline to week 3 and week 12

Each symptom will be scored in a numeric scale from 0 to 3, as shown below:

0 Absence. The symptom is not present

1. The symptom is of mild intensity, without interfering in the patient's activity

2. The symptom is of moderate intensity, causing obvious discomfort to the patient

3. The symptom is stated as very irritating and severe in intensity

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Change in Pruritus or Itching From Baseline to Week 3 and Week 12 Changes between baseline and week 3	0.0 units on a scale Interval 0.0 to 1.0	0.0 units on a scale Interval -1.0 to 2.0
Change in Pruritus or Itching From Baseline to Week 3 and Week 12 Changes between baseline and week 12	0.0 units on a scale Interval 0.0 to 2.0	0.0 units on a scale Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: week 3 and week 12 vs baseline

Population: postmenopausal women

Change in vaginal dryness puntuation score from baseline to w3 and w12

Each symptom will be scored in a numeric scale from 0 to 3, as shown below:

0 Absence. The symptom is not present

1. The symptom is of mild intensity, without interfering in the patient's activity

2. The symptom is of moderate intensity, causing obvious discomfort to the patient

3. The symptom is stated as very irritating and severe in intensity

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Changes in Vaginal Dryness Change between baseline and week 12	2.0 units on a scale Interval 1.0 to 2.0	1.0 units on a scale Interval 1.0 to 1.0
Changes in Vaginal Dryness Change between baseline and week 3	1.0 units on a scale Interval 1.0 to 2.0	1.0 units on a scale Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: week 3 and week 12 vs baseline

Population: postmenopausal women

Changes in Symptoms of vaginal atrophy (vaginal dryness, dyspareunia and pruritus) at week 3 and week 12 vs baseline.

Each symptom will be scored in a numeric scale from 0 to 3, as shown below:

0 Absence. The symptom is not present

1. The symptom is of mild intensity, without interfering in the patient's activity

2. The symptom is of moderate intensity, causing obvious discomfort to the patient

3. The symptom is stated as very irritating and severe in intensity A Global Symptoms Score will be calculated by summing the intensities of all the three symptoms of vaginal atrophy in a certain time point, thus ranging between 0 and 9.

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Changes in Total Score of Symptoms of Vaginal Atrophy Change between baseline and week 3	3.0 score on a scale Interval 2.0 to 4.5	1.0 score on a scale Interval 0.5 to 3.0
Changes in Total Score of Symptoms of Vaginal Atrophy Change between baseline and week 12	4.5 score on a scale Interval 3.0 to 7.0	2.0 score on a scale Interval 1.5 to 4.0

SECONDARY outcome

Timeframe: week 3 and week 12 vs baseline

Population: postmenopausal women

It will be scored by the investigator on a numerical scale in accordance with their presence and degree of severity as follows:

0 Absence. The sign is not present.

1. The sign is present and is considered a mild alteration

2. The sign is present and is considered a moderate alteration

3. The sign is present and is considered a severe alteration

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Changes in Dryness of the Mucosa Changes between baseline and week 3	2.0 score on a scale Interval 1.0 to 2.0	1.0 score on a scale Interval 0.0 to 1.0
Changes in Dryness of the Mucosa Changes between baseline and week 12	2.0 score on a scale Interval 1.0 to 2.0	1.0 score on a scale Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: from baseline to week 3 and 12

Population: Postmenopausal women

It will be scored by the investigator on a numerical scale in accordance with their presence and degree of severity as follows:

0 Absence. The sign is not present.

1. The sign is present and is considered a mild alteration

2. The sign is present and is considered a moderate alteration

3. The sign is present and is considered a severe alteration

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Changes in Fragility of the Mucosa [Time Frame: Week 3 and Week 12 vs Baseline] Changes from baseline to week 3	1.0 score on a scale Interval 0.0 to 2.0	0.0 score on a scale Interval 0.0 to 1.0
Changes in Fragility of the Mucosa [Time Frame: Week 3 and Week 12 vs Baseline] Changes from baseline to week 12	1.5 score on a scale Interval 1.0 to 2.0	0.5 score on a scale Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: week 3 and week 12 vs baseline

Population: postmenopausal women

It will be scored by the investigator on a numerical scale in accordance with their presence and degree of severity as follows:

0 Absence. The sign is not present.

1. The sign is present and is considered a mild alteration

2. The sign is present and is considered a moderate alteration

3. The sign is present and is considered a severe alteration

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Changes in Vaginal Mucosa With Flattening of Folds or Thinning Change between baseline and week 3	1.0 score on a scale Interval 1.0 to 2.0	0.0 score on a scale Interval 0.0 to 0.0
Changes in Vaginal Mucosa With Flattening of Folds or Thinning Change between baseline and week 12	1.0 score on a scale Interval 1.0 to 2.0	0.0 score on a scale Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: week 3 and week 12 vs baseline

Population: postmenopausal women

The signs evaluated Will be the following: vaginal mucosa with flattening of folds or thinning, dryness of the mucosa and Fragility of the mucosa.

It will be scored by the investigator on a numerical scale in accordance with their presence and degree of severity as follows:

0 Absence. The sign is not present.

1. The sign is present and is considered a mild alteration

2. The sign is present and is considered a moderate alteration

3. The sign is present and is considered a severe alteration A Total Signs Score will be calculated by summing the intensities of all the three signs of vaginal atrophy in a certain time point, thus ranging between 0 and 9.

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Changes in Total Score of Signs of Vaginal Atrophy Between Week 3 and Week 12 to Baseline Change between baseline and week 3	4.0 score on a scale Interval 2.0 to 5.0	1.0 score on a scale Interval 0.0 to 2.0
Changes in Total Score of Signs of Vaginal Atrophy Between Week 3 and Week 12 to Baseline Change between baseline and week 12	5.0 score on a scale Interval 4.0 to 6.0	1.0 score on a scale Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: week 3 and week 12 vs baseline

Population: postmenopausal women

Vaginal cytology sample to evaluate the vaginal Maturation Value. For the cytologic evaluation, the number of parabasal, intermediate and superficial cells will be calculated in duplicate on 100 consecutive cells of vaginal cytology. The average of the two percentages obtained for each cell type will be calculated, which will serve to determine the maturation value (MV) based on the following formula:

0.2 x (% parabasal) + 0.6 x (% intermediate) + 1.0 x (% superficial).

Outcome measures

Measure	0.005% Estriol Vaginal Gel n=50 Participants Route: 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	Placebo Vaginal Gel n=11 Participants Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Changes in Vaginal Maturation Value Change between baseline and week 3	-62.0 % of cells Interval -70.04 to -37.8	-0.6 % of cells Interval -11.6 to 2.0
Changes in Vaginal Maturation Value Change between baseline and week 12	-37.2 % of cells Interval -55.0 to -5.4	-1.0 % of cells Interval -36.4 to 1.4

Adverse Events

0.005% Estriol Vaginal Gel

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo Vaginal Gel

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	0.005% Estriol Vaginal Gel n=50 participants at risk Route: 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	Placebo Vaginal Gel n=11 participants at risk Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	2.0% 1/50 • From baseline to last visit (up to 16 weeks) AE: Any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.	0.00% 0/11 • From baseline to last visit (up to 16 weeks) AE: Any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.

Other adverse events

Measure	0.005% Estriol Vaginal Gel n=50 participants at risk Route: 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	Placebo Vaginal Gel n=11 participants at risk Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration Placebo
Infections and infestations Urinary tract infection	6.0% 3/50 • From baseline to last visit (up to 16 weeks) AE: Any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.	9.1% 1/11 • From baseline to last visit (up to 16 weeks) AE: Any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.

Additional Information

Concepción Nieto Magro

ITF Research Pharma SLU

Phone: 0034916572323

Email: concepcion@itfsp.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER