Vasomotoric Symptoms Study of a 0.5 mg Estradiol and 2.5 mg Dydrogesterone Combination

Study Overview
=================
Brief Summary
-----------------
To demonstrate efficacy of continuous combined 0.5 mg estradiol and 2.5 mg dydrogesterone versus placebo in the treatment of vasomotor symptoms after a treatment period of 3 months and to investigate the bleeding pattern over a treatment period of one year

Official Title
-----------------
A Randomized, Placebo-Controlled, Double-Blind, Multi-National Study to Demonstrate Efficacy of Continuous Combined 0.5 mg Estradiol and 2.5 mg Dydrogesterone in the Treatment of Vasomotor Symptoms in Postmenopausal Women in Comparison to Placebo Over 3 Months, and to Investigate the Bleeding Pattern Over a Double-Blind Treatment Period of One Year Compared With Continuous Combined 1 mg Estradiol and 5 mg Dydrogesterone

Conditions
-----------------
Postmenopause

Intervention / Treatment
-----------------
* Drug: continuous combined estradiol and dydrogesterone
* Drug: continuous combined estradiol and dydrogesterone
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Non-hysterectomised postmenopausal women Amenorrhoea for >= 12 months Serum estradiol and follicle stimulating hormone (FSH) in the postmenopausal range Exclusion Criteria: Known hypersensitivity to estradiol, dydrogesterone or any of the excipients of the study medication Baseline endometrial biopsy result other than described in the inclusion criteria (no endometrial tissue for diagnosis, hyperplasia, carcinoma). Insufficient endometrial tissue for diagnosis obtained at baseline biopsy and endometrial thickness >= 5 mm (double layer) by transvaginal ultrasound. The presence of an endometrial polyp at baseline. Abnormal (un-investigated and/or unexplained) vaginal bleeding in the last 12 months prior to Screening Visit (Visit 1). Estradiol pellet/implant therapy during the past 6 months. Previous systemic unopposed estrogen replacement therapy over 6 months or more. History or presence of malignant neoplasms other than basal or spinal cell carcinoma of the skin

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: continuous combined estradiol and dydrogesterone<br>* 0.5 Mg Estradiol and 2.5 Mg Dydrogesterone<br>|
| Active Comparator: B<br> | Drug: continuous combined estradiol and dydrogesterone<br>* 1 Mg Estradiol and 5 Mg Dydrogesterone<br>|
| Placebo Comparator: C<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the number of moderate to severe hot flushes from baseline to week 13 |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the number of hot flushes from baseline to week 13; Change in the number of hot flushes and moderate to severe hot flushes from baseline to weeks 4 and 8; |  | 12 weeks | 
| Change in the Menopause Rating Scale from baseline to weeks 4 and 13; |  | 52 weeks | 
| Number of days with bleeding/spotting; Number of bleeding/spotting episodes; Number of days with a certain bleeding intensity (e.g. bleeding intensity =2); |  | 52 weeks | 
| Length of bleeding free intervals; Amenorrhoea yes/no (absence of spotting and bleeding); Absence of bleeding yes/no; |  | 52 weeks | 
| QualiPause Inventory 7D: weighted sum score of the symptoms |  | 52 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hormone replacement, vasomotoric symptoms, bleeding pattern