Study to Investigate the Pharmacokinetics & Safety Following One Application of 3 Different Doses 0.5,0.75,& 1.25 gm,a Transdermal Estradiol Cream (VML-0203), in Comparison to a Single Dose of EstroGel 1.25 gm to Healthy Post-menopausal Women.

Study Overview
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Brief Summary
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This study is a Phase I, Randomized, Open-Label, Single Center, Cross-over Study to Investigate the Pharmacokinetics and Safety following a Single Application of Three Different Doses 0.5 gm (0.5 mg estradiol), 0.75 gm (0.75 mg estradiol) and 1.25 gm (1.25 mg estradiol), a Transdermal Estradiol Cream (VML-0203), in comparison to a single dose of EstroGelTM 1.25 gm (1 unit/0.75 mg of estradiol) to healthy post-menopausal women.

Official Title
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A Phase I, Randomized, Open-Label, Single Center, Cross-over Study to Investigate the Pharmacokinetics and Safety Following a Single Application of Three Different Doses 0.5 gm (0.5 mg Estradiol), 0.75 gm (0.75 mg Estradiol) and 1.25 gm (1.25 mg Estradiol), a Transdermal Estradiol Cream (VML-0203), in Comparison to a Single Dose of EstroGelTM 1.25 gm (1 Unit/0.75 mg of Estradiol) to Healthy Post-menopausal Women.

Conditions
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Menopause

Intervention / Treatment
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* Drug: Estrogel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy post-menopausal (surgical or natural) female defined as: No menstrual period within the past year before study entry. Serum estradiol levels between 0-20 pg/ml. FSH levels greater than 25.8 mIU/ml. Greater than 45 years of age or if surgical menopausal, > 30 yrs. of age. Have a body mass index (BMI) between 18 and 30 kg/m2. Have had a normal PAP smear test result in line with the following guidelines: aged 30 to 49 - within the last 3 years aged 50 to 65 - within the last 5 years Exclusion Criteria: Is pregnant (urine pregnancy test at screening) or lactating. Has evidence of drug or alcohol abuse. Have used hormonal replacement or vaginal hormonal therapy within the past three months before study entry. Have used estrogen pellet therapy or progestin injectable drug therapy within the past three months before study entry. Has contraindications to HRT use, including: unexplained vaginal bleeding, liver disease, breast or endometrial cancer, venous thromboembolic events. Any subjects with an obvious presence of skin conditions, excessive hair at the application sites (no shaving), scar tissue, tattoo, or coloration that would interfere with application of IMP, skin assessment, or reactions to drug. Presence of open sores at the application sites. Any subjects with a history of significant skin disorder. Smoker.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5 gm of EstroCream (VML-0203)<br> | Drug: Estrogel<br>* Each subject will receive the following IMPs in accordance with the randomisation code: Test IMP: a single-dose of 0.5g, 0.75g and 1.25g VML-0203 cream Reference IMP: a single-dose of 1.25g EstroGel<br>* Other names: EstroCream;|
| Experimental: 0.75 gm of EstroCream (VML-0203)<br> | Drug: Estrogel<br>* Each subject will receive the following IMPs in accordance with the randomisation code: Test IMP: a single-dose of 0.5g, 0.75g and 1.25g VML-0203 cream Reference IMP: a single-dose of 1.25g EstroGel<br>* Other names: EstroCream;|
| Experimental: 1.25 gm of EstroCream (VML-0203)<br> | Drug: Estrogel<br>* Each subject will receive the following IMPs in accordance with the randomisation code: Test IMP: a single-dose of 0.5g, 0.75g and 1.25g VML-0203 cream Reference IMP: a single-dose of 1.25g EstroGel<br>* Other names: EstroCream;|
| Active Comparator: 1.25 EstroGel<br> | Drug: Estrogel<br>* Each subject will receive the following IMPs in accordance with the randomisation code: Test IMP: a single-dose of 0.5g, 0.75g and 1.25g VML-0203 cream Reference IMP: a single-dose of 1.25g EstroGel<br>* Other names: EstroCream;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the bio-availability of estradiol and estrone. | Blood samples will be analysed. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To provide general safety information for VML-0203. | Application site inspections will be assessed. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoestrogenism, Menopausal hormone therapy