DHEA Bioavailability Following Administration of Vaginal Suppositories in Post-Menopausal Women With Vaginal Atrophy

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the systemic bioavailability of DHEA and its metabolites and the pharmacokinetics of vaginal suppositories at four different DHEA concentration.

Detailed Description
-----------------
Humans, are unique among animal species in having adrenals that secrete large amounts of the inactive precursor steroids dehydroepiandrosterone (DHEA) and especially its sulfate DHEA-S. The marked reduction in the formation of DHEA-S by the adrenals during aging results in a dramatic fall in the formation of androgens and estrogens in peripheral target tissues, a situation that has been proposed to be associated with age-related diseases including skin atrophy, insulin resistance and obesity. Much attention has been given to the benefits of DHEA administered to postmenopausal women, especially on the bone, skin, vagina and well being after oral as well as percutaneous administration of the precursor steroid. Therefore, this study proposes to evaluate the systemic bioavailability and the effectiveness of 1.3 mL vaginal suppositories of DHEA at 4 different concentrations (0.0%, 0.5%, 1.0% et 1.8%) following 1 week administration of vaginal suppositories in post-menopausal women with vaginal atrophy. This is a phase I, randomized, placebo-controlled, double-blind study.

Official Title
-----------------
DHEA Bioavailability Following Administration of Vaginal Suppositories in Post-Menopausal Women With Vaginal Atrophy-Phase I Randomized,Placebo-Controlled, Double-Blind Study.

Conditions
-----------------
Vaginal Atrophy

Intervention / Treatment
-----------------
* Drug: DHEA
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Postmenopausal women, Experiencing one symptom of vaginal atrophy (vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity or vaginal bleeding associated with sexual activity, Women having a low maturation index and a vaginal pH above 5, Endometrial thickness of 4 mm or less at transvaginal ultrasonography, Body weight within 18.5 and 32.0 according to body mass index. Exclusion Criteria: Undiagnosed abnormal genital bleeding, Active or history of thromboembolic disease, Significant metabolic or endocrine disease, Significant complication on previous hormonal therapy, Use of hormonal implants within 6 months prior to study entry, Use of oral estrogen, progestin or DHEA in the 8 weeks prior to baseline, Use of natural (phytoestrogens) or herbal products in the 2 weeks prior to baseline, Chronic use of corticosteroids, Hypertension not controlled by standard therapy.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo suppository; once daily for 7 days. | Drug: Placebo<br>* Placebo<br>|
| Experimental: DHEA 0.50%<br>DHEA 0.50% (6.5 mg) suppository; once daily for 7 days. | Drug: DHEA<br>* DHEA<br>* Other names: dehydroepiandrosterone; prasterone;|
| Experimental: DHEA 1.0%<br>DHEA 1.0% (13 mg) suppository; once daily for 7 days. | Drug: DHEA<br>* DHEA<br>* Other names: dehydroepiandrosterone; prasterone;|
| Experimental: DHEA 1.8%<br>DHEA 1.8% (23.4 mg) suppository; once daily for 7 days. | Drug: DHEA<br>* DHEA<br>* Other names: dehydroepiandrosterone; prasterone;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The evaluation of the systemic bioavailability of DHEA and its metabolites. |  | Day 1-2 and Day 7-8 | 
| The pharmacokinetics of vaginal suppositories at four different DHEA concentrations. |  | Day 1-2 and Day 7-8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and tolerance of the suppositories. |  | Day 1 to Day 8 (plus follow-up of Adverse Events for 30 days after last dose) | 
| The effect of treatment on maturation index and value |  | Day 7 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vaginal atrophy, DHEA, Prasterone, Menopause