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Randomized, double-blind, placebo-controlled multicentre study, with parallel groups, to determine the efficacy and safety of a new low-concentration estriol formulation (ITFE-2026 0.005%) for application by vaginal route in the treatment of postmenopausal vaginal atrophy.
Primary objective:
• To evaluate the efficacy of 0.005% Estriol vaginal gel by evaluation of the change in the maturation value of the vaginal epithelium (MV) after 12 weeks of treatment.
Secondary objectives:
This is a randomized, double-blind, placebo-controlled multicentre study, with parallel groups, to determine the efficacy and safety of a new low-concentration estriol formulation (ITFE-2026 0.005%) for application by vaginal route in the treatment of postmenopausal vaginal atrophy.
Eligible patients were randomised in a ratio of 2:1 to 0.005% Estriol vaginal gel : placebo. Each patient was treated for 12 weeks followed by a one-month observational period. The patients attended the study centre at baseline and at 3, 8 and 12 weeks after start of treatment. Vaginal cytology was performed at baseline and at weeks 3 and 12; the vaginal pH and the signs and symptoms of vaginal atrophy were recorded at baseline and after 3 and 12 weeks of treatment. Vital signs, gynaecological exploration and changes in health and concomitant medication were documented at each visit. Transvaginal ultrasound was performed at screening and week 12. The investigators telephoned the patient approximately one month after the final visit to check if the patient had experienced any adverse events since the final visit. Two independent cytopathologists assessed the maturation value of each cytology sample at the end of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 0.005% Estriol group | Experimental | 0.005% Estriol (50 μg/g) gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. |
|
| Placebo group | Placebo Comparator | Placebo gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Estriol | Drug | Gel for vaginal application |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 12 in Maturation Value (MV) After 12 Weeks of Treatment | Maturation value (MV) is a cytologic parameter indicative of the degree of atrophy of the vaginal mucosa. This variable is a quantitative parameter indicative of the cytological status of the vaginal epithelium. The number of parabasal, intermediate and superficial cells was calculated from 300 consecutive cells of the samples of vaginal cytology, and the percentages of each type of cells obtained. The Maturation Value was obtained based on the following formula: 0.2 x (% parabasal) + 0.6 x (% intermediate) + 1.0 x (% superficial). The higher the value, the higher the maturation degree. | At week 12/Early withdrawal |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 12 of the Vaginal pH After the 12-week Observation Period | As a consequence of reduced estrogen levels, the vaginal mucosa occurs loses its rugosity, its thickness decreases, and it becomes pale and friable. The production of glycogen decreases, which determines vaginal pH alkalinization. | At week 12 /early withdrawal |
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Main Inclusion Criteria:
Women of any age.
Menopause with amenorrhea time ≥ 2 years, either due to natural or surgical menopause (bilateral oophorectomy).
Presence of symptoms and signs of atrophy of the vaginal mucosa including at minimum vaginal dryness as a symptom stated by the patient, together with at least one sign of the disease verified by the investigator.
Patients with mammography carried out in the period of one year prior to inclusion in the study.
Patients able to understand the nature and purpose of the study, to cooperate with the investigator and meet the study requirements.
Patients who gave written informed consent to participate in the study.
Exclusion Criteria:
Patients with contraindications for hormone therapy with estrogens because they had a history of:
Patients who had abnormal laboratory values at the start of the study that the investigator considered clinically relevant for the purposes of the present study.
Patients with signs and symptoms suggestive of infection of the genital or urinary tract at the start of the study.
Patients with any medical-surgical pathology, which was uncontrolled at the time of inclusion in the study.
Patients with any acute process whose handling or evolution the investigator considered could interfere in the development of the study.
Patients with endometrial thickness equal to or greater than 4 mm measured by transvaginal ultrasound.
Patients with grade II or higher uterovaginal prolapse.
Patients who had received any type of vulvovaginal treatment in the 15 days prior to the start of the study.
Patients who had received phytoestrogens in the period of one month prior to the start of the study, including administration by vaginal route.
Patients who had received hormone therapy in the period of 3 months prior to the start of the study, including the administration of estrogens by vaginal route.
Patients on treatment with drugs described in section 7.3 of the protocol
Patients with a history of allergy to any of the components of the medication under study (see the composition in section 3.3. of the protocol).
Patients who had participated in the experimental evaluation of any drug during the 8 weeks before the start of the present study.
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| Name | Affiliation | Role |
|---|---|---|
| Javier Ferrer Barriendos, MD, PhD | Hospital Universitario Central de Asturias | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Sierrallana | Torrelavega | Cantabria | 39300 | Spain | ||
| Hospital Ruber Internacional |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22914208 | Result | Cano A, Estevez J, Usandizaga R, Gallo JL, Guinot M, Delgado JL, Castellanos E, Moral E, Nieto C, del Prado JM, Ferrer J. The therapeutic effect of a new ultra low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of postmenopausal vaginal atrophy: results from a pivotal phase III study. Menopause. 2012 Oct;19(10):1130-9. doi: 10.1097/gme.0b013e3182518e9a. |
| Label | URL |
|---|---|
| The therapeutic effect of a new ultra low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of postmenopausal vaginal atrophy: results from a pivotal phase III study | View source |
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There were 167 patients enrolled in the study; 114 patients were randomized to the Estriol group and 53 to the placebo group.
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| ID | Title | Description |
|---|---|---|
| FG000 | 0.005% Estriol Group | 0.005% Estriol (50 μg/g) gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. Estriol: Gel for vaginal application |
| FG001 | Placebo Group | Placebo gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. Placebo: Gel for vaginal application |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intention-to-treat population (ITT): all randomized women that received at least one dose of the study drug (Estriol gel vaginal 0.005% or placebo) after the randomization.
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| ID | Title | Description |
|---|---|---|
| BG000 | 0.005% Estriol Group | 0.005% Estriol (50 μg/g) gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. Estriol: Gel for vaginal application |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 Maturation Value (MV) After 12 Weeks of Treatment | Maturation value (MV) is a cytologic parameter indicative of the degree of atrophy of the vaginal mucosa. This variable is a quantitative parameter indicative of the cytological status of the vaginal epithelium. The number of parabasal, intermediate and superficial cells was calculated from 300 consecutive cells of the samples of vaginal cytology, and the percentages of each type of cells obtained. The Maturation Value was obtained based on the following formula: 0.2 x (% parabasal) + 0.6 x (% intermediate) + 1.0 x (% superficial). The higher the value, the higher the maturation degree. | Intention-to-treat population (ITT): all randomized women that received at least one dose of the study drug (Estriol gel vaginal 0.005% or placebo) after the randomization. | Posted | Mean | Standard Deviation | vaginal health index | At week 12/Early withdrawal |
|
Throughout the study (baseline, day 1, week 3, week 8, and week 12)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 0.005% Estriol Group | 0.005% Estriol (50 μg/g) gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. Estriol: Gel for vaginal application |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Crural hernia | Musculoskeletal and connective tissue disorders | MedDRA 6.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urinary tract infection | Infections and infestations | MedDRA 6.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Concepción Nieto | Italfarmaco | +34 91 657 23 23 | cnieto@itfsp.com |
Not provided
| ID | Term |
|---|---|
| D004964 | Estriol |
| ID | Term |
|---|---|
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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The study drug, 0.005% Estriol vaginal gel, and its vehicle in gel (placebo) will have identical appearance, same aroma and the same texture in order to maintain the double blind.
| Placebo | Other | Gel for vaginal application |
|
| Number of Participants With Variation of the Individual Signs and Symptoms of Vaginal Atrophy After the 12-week Observation Period | Signs and symptoms of vaginal atrophy are: vaginal dryness, pruritus or itching, burning, dyspareunia, dysuria. For each of these symptoms the subject indicates one the following status: present, absent, missing. Symptoms of vaginal atrophy were scored by the patients in a numeric scale from 0 to 3, as shown below: 0 Absence. The symptom is not present
Signs of vaginal atrophy were evaluated by the investigator and scored on a numerical scale as shown below: 0 Absence. The symptom is not present
| At baseline and at 12 weeks / early withdrawal |
| Change From Baseline to Week 3 in Maturation Value (MV) After 3 Weeks of Treatment | Maturation value (MV) is a cytologic parameter indicative of the degree of atrophy of the vaginal mucosa. This variable is a quantitative parameter indicative of the cytological status of the vaginal epithelium. The number of parabasal, intermediate and superficial cells was calculated from 300 consecutive cells of the samples of vaginal cytology, and the percentages of each type of cells obtained. The Maturation Value was obtained based on the following formula: 0.2 x (% parabasal) + 0.6 x (% intermediate) + 1.0 x (% superficial). The higher the value, the higher the maturation degree. | At week 3/ early withdrawal |
| Change From Baseline to Week 3 of the Vaginal pH After the 3-week Observation Period | As a consequence of reduced estrogen levels, the vaginal mucosa occurs loses its rugosity, its thickness decreases, and it becomes pale and friable. The production of glycogen decreases, which determines vaginal pH alkalinization. | At week 3 / early withdrawal |
| Number of Participants With Variation of the Individual Signs and Symptoms of Vaginal Atrophy After the 3-week Observation Period | Signs and symptoms of vaginal atrophy are: vaginal dryness, pruritus or itching, burning, dyspareunia, dysuria. For each of these symptoms the subject indicates one the following status: present, absent, missing. Symptoms of vaginal atrophy were scored by the patients in a numeric scale from 0 to 3, as shown below: 0 Absence. The symptom is not present
Signs of vaginal atrophy were evaluated by the investigator and scored on a numerical scale as shown below: 0 Absence. The symptom is not present
| At 3 weeks |
| Madrid |
| Castiglia |
| 28034 |
| Spain |
| Centre Mèdic Teknon S.L. | Barcelona | Catalonia | 08022 | Spain |
| Fundació de Gestió Sanità ria de l'Hospital de la Santa. Creu i Sant Pau | Barcelona | Catalonia | 08025 | Spain |
| Complejo Hospitalario Virgen de las Nieves | Granada | 18014 | Spain |
| Fundación Jiménez DÃaz | Madrid | 28040 | Spain |
| Complejo Universitario La Paz | Madrid | 28046 | Spain |
| Hospital Universitario Virgen de la Arrixaca | Murcia | 30120 | Spain |
| Hospital Universitario Central de Asturias | Oviedo | 33006 | Spain |
| Hospital ClÃnico Universitario de Valencia | Valencia | 46010 | Spain |
| Hospital la Ribera de Alzira | Valencia | 46600 | Spain |
| Hospital do Meixoeiro | Vigo | 36200 | Spain |
| Protocol Violation |
|
| Withdrawal by Subject |
|
| Lost to Follow-up |
|
| Personal problems |
|
| Previous planned surgery |
|
| Placebo Group |
Placebo gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. Placebo: Gel for vaginal application |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
0.005% Estriol (50 μg/g) gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. Estriol: Gel for vaginal application |
| OG001 | Placebo Group | Placebo gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. Placebo: Gel for vaginal application |
|
|
|
| Secondary | Change From Baseline to Week 12 of the Vaginal pH After the 12-week Observation Period | As a consequence of reduced estrogen levels, the vaginal mucosa occurs loses its rugosity, its thickness decreases, and it becomes pale and friable. The production of glycogen decreases, which determines vaginal pH alkalinization. | Intention-to-treat population (ITT): all randomized women that received at least one dose of the study drug (Estriol gel vaginal 0.005% or placebo) after the randomization. | Posted | Mean | Standard Deviation | pH units | At week 12 /early withdrawal |
|
|
|
|
| Secondary | Number of Participants With Variation of the Individual Signs and Symptoms of Vaginal Atrophy After the 12-week Observation Period | Signs and symptoms of vaginal atrophy are: vaginal dryness, pruritus or itching, burning, dyspareunia, dysuria. For each of these symptoms the subject indicates one the following status: present, absent, missing. Symptoms of vaginal atrophy were scored by the patients in a numeric scale from 0 to 3, as shown below: 0 Absence. The symptom is not present
Signs of vaginal atrophy were evaluated by the investigator and scored on a numerical scale as shown below: 0 Absence. The symptom is not present
| Intention-to-treat population (ITT): all randomized women that received at least one dose of the study drug (Estriol gel vaginal 0.005% or placebo) after the randomization. | Posted | Count of Participants | Participants | At baseline and at 12 weeks / early withdrawal |
|
|
|
| Secondary | Change From Baseline to Week 3 in Maturation Value (MV) After 3 Weeks of Treatment | Maturation value (MV) is a cytologic parameter indicative of the degree of atrophy of the vaginal mucosa. This variable is a quantitative parameter indicative of the cytological status of the vaginal epithelium. The number of parabasal, intermediate and superficial cells was calculated from 300 consecutive cells of the samples of vaginal cytology, and the percentages of each type of cells obtained. The Maturation Value was obtained based on the following formula: 0.2 x (% parabasal) + 0.6 x (% intermediate) + 1.0 x (% superficial). The higher the value, the higher the maturation degree. | Intention-to-treat population (ITT): all randomized women that received at least one dose of the study drug (Estriol gel vaginal 0.005% or placebo) after the randomization. | Posted | Mean | Standard Deviation | vaginal health index | At week 3/ early withdrawal |
|
|
|
|
| Secondary | Change From Baseline to Week 3 of the Vaginal pH After the 3-week Observation Period | As a consequence of reduced estrogen levels, the vaginal mucosa occurs loses its rugosity, its thickness decreases, and it becomes pale and friable. The production of glycogen decreases, which determines vaginal pH alkalinization. | Intention-to-treat population (ITT): all randomized women that received at least one dose of the study drug (Estriol gel vaginal 0.005% or placebo) after the randomization. | Posted | Mean | Standard Deviation | pH units | At week 3 / early withdrawal |
|
|
|
|
| Secondary | Number of Participants With Variation of the Individual Signs and Symptoms of Vaginal Atrophy After the 3-week Observation Period | Signs and symptoms of vaginal atrophy are: vaginal dryness, pruritus or itching, burning, dyspareunia, dysuria. For each of these symptoms the subject indicates one the following status: present, absent, missing. Symptoms of vaginal atrophy were scored by the patients in a numeric scale from 0 to 3, as shown below: 0 Absence. The symptom is not present
Signs of vaginal atrophy were evaluated by the investigator and scored on a numerical scale as shown below: 0 Absence. The symptom is not present
| Intention-to-treat population (ITT): all randomized women that received at least one dose of the study drug (Estriol gel vaginal 0.005% or placebo) after the randomization. | Posted | Count of Participants | Participants | At 3 weeks |
|
|
|
| 0 |
| 114 |
| 1 |
| 114 |
| 50 |
| 114 |
| EG001 | Placebo Group | Placebo gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. Placebo: Gel for vaginal application | 0 | 53 | 0 | 53 | 20 | 53 |
| Nasopharyngitis | Infections and infestations | MedDRA 6.1 | Systematic Assessment |
|
| Candidiasis | Infections and infestations | MedDRA 6.1 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 6.1 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 6.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 6.1 | Systematic Assessment |
|
| Genital herpes | Infections and infestations | MedDRA 6.1 | Systematic Assessment |
|
| Synusitis | Infections and infestations | MedDRA 6.1 | Systematic Assessment |
|
| Vulval abscess | Infections and infestations | MedDRA 6.1 | Systematic Assessment |
|
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA 6.1 | Systematic Assessment |
|
| Vulvovaginal pruritus | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Breast pain | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Vaginal discharge | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Adnexa uteri pain | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Bartholinitis | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Breast discomfort | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Breast swelling | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Endometrial hypertrophy | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Genital rash | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Metrorrhagia | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Pruritus genital | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Vulvovaginal discomfort | Reproductive system and breast disorders | MedDRA 6.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Sensation of heavyness | Musculoskeletal and connective tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Intervertebral disk protrusion | Musculoskeletal and connective tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Hyperhydrosis | Skin and subcutaneous tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Prurigo | Skin and subcutaneous tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Pruritus generalized | Skin and subcutaneous tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 6.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 6.1 | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 6.1 | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA 6.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 6.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 6.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 6.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 6.1 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 6.1 | Systematic Assessment |
|
| Melaena | Gastrointestinal disorders | MedDRA 6.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 6.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 6.1 | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 6.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 6.1 | Systematic Assessment |
|
| Application site pruritus | General disorders | MedDRA 6.1 | Systematic Assessment |
|
| Application site irritation | General disorders | MedDRA 6.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 6.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 6.1 | Systematic Assessment |
|
| Inflammation | General disorders | MedDRA 6.1 | Systematic Assessment |
|
| Peripheral coldness | General disorders | MedDRA 6.1 | Systematic Assessment |
|
| Swelling | General disorders | MedDRA 6.1 | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA 6.1 | Systematic Assessment |
|
| Labile hypertension | Vascular disorders | MedDRA 6.1 | Systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 6.1 | Systematic Assessment |
|
| Fluid retention | Metabolism and nutrition disorders | MedDRA 6.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 6.1 | Systematic Assessment |
|
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA 6.1 | Systematic Assessment |
|
| Overweight | Metabolism and nutrition disorders | MedDRA 6.1 | Systematic Assessment |
|
| Motion sickness | Ear and labyrinth disorders | MedDRA 6.1 | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA 6.1 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 6.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 6.1 | Systematic Assessment |
|
| Dysthymic disorder | Psychiatric disorders | MedDRA 6.1 | Systematic Assessment |
|
| Joint sprain | Injury, poisoning and procedural complications | MedDRA 6.1 | Systematic Assessment |
|
| Nerve root injury lumbar | Injury, poisoning and procedural complications | MedDRA 6.1 | Systematic Assessment |
|
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA 6.1 | Systematic Assessment |
|
| Bunion operation | Surgical and medical procedures | MedDRA 6.1 | Systematic Assessment |
|
| Wisdom teeth removal | Surgical and medical procedures | MedDRA 6.1 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 6.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 6.1 | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA 6.1 | Systematic Assessment |
|
| Leukocyturia | Renal and urinary disorders | MedDRA 6.1 | Systematic Assessment |
|
Not provided
Not provided
| D011083 |
| Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| Vaginal dryness - Baseline - absent |
|
|
| Vaginal dryness - Baseline - missing |
|
|
| Vaginal dryness - week 12 - present |
|
|
| Vaginal dryness - week 12 - absent |
|
|
| Vaginal dryness - week 12 - missing |
|
|
| Pruritus - Baseline - present |
|
|
| Pruritus - Baseline - absent |
|
|
| Pruritus - Baseline - missing |
|
|
| Pruritus - week 12 - present |
|
|
| Pruritus - week 12 - absent |
|
|
| Pruritus - week 12 - missing |
|
|
| Burning - Baseline - present |
|
|
| Burning - Baseline - absent |
|
|
| Burning - Baseline - missing |
|
|
| Burning - week 12 - present |
|
|
| Burning - week 12 - absent |
|
|
| Burning - week 12 - missing |
|
|
| Dyspareunia - Baseline - present |
|
|
| Dyspareunia - Baseline - absent |
|
|
| Dyspareunia - Baseline - missing |
|
|
| Dyspareunia - week 12 - present |
|
|
| Dyspareunia - week 12 - absent |
|
|
| Dyspareunia - week 12 - missing |
|
|
| Dysuria - Baseline - present |
|
|
| Dysuria - Baseline - absent |
|
|
| Dysuria - Baseline - missing |
|
|
| Dysuria - week 12 - present |
|
|
| Dysuria - week 12 - absent |
|
|
| Dysuria - week 12 - missing |
|
|
| Vaginal dryness - Baseline - absent |
|
|
| Vaginal dryness - Baseline - missing |
|
|
| Vaginal dryness - week 3 - present |
|
|
| Vaginal dryness - week 3 - absent |
|
|
| Vaginal dryness - week 3 - missing |
|
|
| Pruritus - Baseline - present |
|
|
| Pruritus - Baseline - absent |
|
|
| Pruritus - Baseline - missing |
|
|
| Pruritus - week 3 - present |
|
|
| Pruritus - week 3 - absent |
|
|
| Pruritus - week 3 - missing |
|
|
| Burning - Baseline - present |
|
|
| Burning - Baseline - absent |
|
|
| Burning - Baseline - missing |
|
|
| Burning - week 3 - present |
|
|
| Burning - week 3 - absent |
|
|
| Burning - week 3 - missing |
|
|
| Dyspareunia - Baseline - present |
|
|
| Dyspareunia - Baseline - absent |
|
|
| Dyspareunia - Baseline - missing |
|
|
| Dyspareunia - week 3 - present |
|
|
| Dyspareunia - week 3 - absent |
|
|
| Dyspareunia - week 3 - missing |
|
|
| Dysuria - Baseline - present |
|
|
| Dysuria - Baseline - absent |
|
|
| Dysuria - Baseline - missing |
|
|
| Dysuria - week 3 - present |
|
|
| Dysuria - week 3 - absent |
|
|
| Dysuria - week 3 - missing |
|
|