E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003690 |
E.1.2 | Term | Atrophic vaginitis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the endometrial hyperplasia rate from endometrial biopsies taken at the beginning and at the end of study treatment (12 months).
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Informed consent to be obtained before any trial related activities. (Trial related activities are any procedure that would not have been performed during normal management of the subject.) 2.Postmenopausal women aged 45 years or older at the time of screening. 3.Postmenopausal women ≥ 2 years after last menstruation; or bilateral oophorectomy performed 2 years or more prior to the time of screening. 4.Serum FSH levels > 40 mIU/ml and estradiol < 20 pg/ml 5.Subject should have at least 1 urogenital symptom of moderate to severe severity as identified by the subject (vaginal dryness, vaginal and/or vulvar irritation/itching, vaginal soreness, dysuria, dyspareunia and vaginal bleeding associated with sexual activity) during the week prior to screening period. 6.≤ 5% superficial cells as assessed by evaluation of vaginal cytology 7.Vaginal pH ≥ 5 8.Endometrial thickness < 4.0 mm (double layer), as measured by transvaginal ultrasound. 9.Normal mammogram within 6 months prior to trial start (Visit 1) or normal mammogram prior to Visit 2 if not available at Visit 1. 10.Subject with an intact uterus, meaning no component removed or destroyed. For example patients who have undergone an endometrial ablation or transcervical resection of the endometrium are not eligible to participate. 11.Good general health, as assessed by the Investigator and based on medical history, and physical and laboratory examinations. 12.No significant illnesses that could interfere with the subject’s participation in the trial, based upon Investigator judgment. 13.Able to comply with the requirements of the trial.
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E.4 | Principal exclusion criteria |
1.Known or suspected allergy to trial product or related products. 2.Known, suspected or past history of breast cancer. 3.Known, suspected or past estrogen dependent neoplasia e.g. endometrial cancer. 4.Endometrial hyperplasia or endometrial polyps diagnosed during the screening period. 5.Abnormal genital bleeding of unknown etiology. 6.Exposure to exogenous sex steroid hormones (estrogen and/or progestin hormone replacement therapy) within past 3 months prior to the screening visit 7.Use of any type of vaginal or vulvar preparations, e.g. pessaries, contraceptive sponges, douches, vaginal moisturizers, or other non-estrogenic medications including K-Y jelly etc., 1 month prior to Visit 2. 8.Hot flushes which require systemic HT treatment. 9.Known insulin dependent or non-insulin dependent diabetes mellitus. 10.Systolic blood pressure (BP) ≥ 160 mm Hg and/or diastolic BP ≥ 100 mm Hg, currently treated or untreated. 11.Active deep venous thrombosis or thromboembolic disorders or a history of these conditions. 12.Active arterial thrombosis or a documented history of this condition. 13.Known or suspected hepatic and/or renal impairment based on medical history, physical examination, and/or laboratory results. 14.Porphyria. 15.Body Mass Index (BMI)> 35.0 kg/m2. 16.Papanicolaou cervical smear presenting PAP class > II. 17.Known or suspected vaginal infection requiring further treatment. 18.Uterovaginal prolapse Grade II-IV POPQ (pelvic organ prolapse qualification scale). 19.Hysterectomy or endometrial ablation 20.Known alcohol or drug abuse, heavy smoking (more than 20 cigarettes a day). 21.Currently using steroid hormones (except topical or inhalation glucocorticoid preparations) and drugs known to significantly influence oestrogen metabolism such as barbiturates, phenytoin, rifampicin, carbamazepine. 22.Previous participation in this trial. 23.Subject who has participated in any other trial involving other investigational products within the last 30 days.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary safety endpoint is the hyperplasia rate at the end of study (12 months). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |