Comparison of Two Vaginal Tablets, Produced at Different Sites, in Postmenopausal Women With Atrophic Vaginitis

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of this trial is to compare the absorption of estradiol after a single dose of two 25 mcg estradiol vaginal tablets, produced at two different production sites, in postmenopausal women with atrophic vaginitis.

Official Title
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An Open Randomized Two-Way Cross-Over Comparative Bioavailability Study to Compare the Extent of Systemic Absorption of Estradiol After a Single Dose Treatment With Two 25 mcg Estradiol Vaginal Tablet Formulations Administered in Postmenopausal Women With Vaginal Atrophy

Conditions
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Menopause, Postmenopausal Vaginal Atrophy

Intervention / Treatment
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* Drug: estradiol, 25 mcg
* Drug: estradiol, 25 mcg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are able to use the German language, spoken and written Postmenopausal women: 5 years or more after last menstruation; or both ovaries surgically removed 2 years or more prior to trial start Availability of a normal mammogram within 1 year prior to trial start Good general health No significant illnesses that could interfere with the subject's participation in the trial, based on the judgment of the physician Exclusion Criteria: Known or suspected allergy to estradiol or related products Known, suspected or past history of breast cancer Abnormal genital bleeding Previous oestrogen and/or progestin hormone replacement therapy Use of any type of vaginal or vulvar preparations, e.g. pessaries, contraceptive sponges, douches, vaginal moisturizers, or other non-oestrogenic medications including K-Y jelly etc., 1 month prior to first planned drug administration Hot flushes which require systemic hormone replacement treatment Known insulin dependent or non-insulin dependent diabetes mellitus Systolic blood pressure (BP) of more than 160 mm Hg and/or diastolic BP or more than 100 mm Hg, currently treated or untreated Active deep venous thrombosis or thromboembolic disorders or a history of these conditions Active arterial thrombosis or a documented history of this condition Known or suspected liver and/or kidney impairment based on medical history, physical examination, and/or laboratory results Known HIV infection based on laboratory result Porphyria Body Mass Index (BMI) above 30.0 kg/m2 Cervical smear presenting PAP of more than class II Known or suspected vaginal infection requiring further treatment Known alcohol or drug abuse, heavy smoking (more than 20 cigarettes a day) Currently using steroid hormones (except topical or inhalation glucocorticoid preparations) and drugs known to significantly influence oestrogen metabolism such as barbiturates, phenytoin, rifampicin, carbamazepine Subject who has participated in any other trial involving other investigational products within the last 30 days prior to the first planned drug administration

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Trial part 1<br> | Drug: estradiol, 25 mcg<br>* Single dose of vaginal tablet containing 25 mcg estradiol (Production site A) followed by another single dose of vaginal tablet containing 25 mcg estradiol (Production site B)<br>|
| Experimental: Trial part 2<br> | Drug: estradiol, 25 mcg<br>* Single dose of vaginal tablet containing 25 mcg estradiol (Production site B) followed by another single dose of vaginal tablet containing 25 mcg estradiol (Production site A)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC(0-t)), maximal concentration (Cmax) of estradiol after baseline correction |  | from dosing to day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events and local tolerability |  | from dosing to day 4 |