DHEA Against Vaginal Atrophy - Safety Study of 12 Months

Study Overview
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Brief Summary
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The purpose of this Phase III trial is to assess the long-term safety of intravaginal dehydroepiandrosterone (DHEA) in non-hysterectomized postmenopausal women with vaginal atrophy aged 40 to 75 years.

Official Title
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DHEA Against Vaginal Atrophy - Safety Study of 12 Months

Conditions
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Vaginal Atrophy

Intervention / Treatment
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* Drug: DHEA


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Postmenopausal women (non-hysterectomized) Women between 40 and 75 years of age. Willing to participate in the study and sign an informed consent. Women who have self-identified symptom(s) of vaginal atrophy. Willing to have endometrial biopsy at screening and end of study (Week 52). Main Exclusion Criteria: Undiagnosed abnormal genital bleeding. Hypertension equal to or above 140/90 mm Hg. The administration of any investigational drug within 30 days of screening visit. Endometrial hyperplasia, cancer or endometrial histology showing proliferative, secretory or menstrual type characteristics at histologic evaluation of endometrial biopsy performed at screening.

Ages Eligible for Study
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Minimum Age: 40 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DHEA<br>0.5% DHEA (intravaginal) | Drug: DHEA<br>* Vaginal suppository containing 0.5% (6.5 mg) DHEA; daily dosing with one suppository for 52 weeks.<br>* Other names: Prasterone, Dehydroepiandrosterone, Vaginorm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term Safety of Intravaginal Prasterone (DHEA): Endometrium | The long-term safety of intravaginal prasterone has been evaluated on different parameters including the endometrium. For this purpose, endometrial biopsies were performed at screening and at the end of the study (52 weeks) or at discontinuation visit for women who were exposed to intravaginal DHEA (prasterone) for at least 12 weeks. At screening, the endometrium had to be atrophic/inactive for women to be enrolled in the study. Only the end-of-study data are presented. | Baseline and Week 52 (or discontinuation) | 
| Long-term Safety of Intravaginal Prasterone (DHEA): Serum Steroid Levels | The long-term safety of intravaginal prasterone has been evaluated on different parameters including the serum levels of DHEA and its metabolites. For this purpose, blood samples were collected at Baseline and different post-Baseline timepoints for the determination of serum steroid levels by a central laboratory using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. The serum levels of dehydroepiandrosterone (DHEA), estradiol (E2) and testosterone (TESTO) obtained at Baseline and Week 52 as well as the change from Baseline to Week 52 are presented. | Baseline and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 52 of Vaginal Cell Maturation (Percentage of Parabasal Cells). | The percentage of parabasal cells was determined from the vaginal smears collected during the study. A 100-cell count was performed by a central laboratory to classify cells as parabasal (P) (including basal), intermediate (I), and superficial (S) squamous cell types. Data obtained at Baseline and Week 52 as well as the change from Baseline to Week 52 are presented. | Baseline and Week 52 | 
| Change From Baseline to Week 52 of Vaginal Cell Maturation (Percentage of Superficial Cells). | The percentage of superficial cells was determined from the vaginal smears collected during the study. A 100-cell count was performed by a central laboratory to classify cells as parabasal (P) (including basal), intermediate (I), and superficial (S) squamous cell types. Data obtained at Baseline and Week 52 as well as the change from Baseline to Week 52 are presented. | Baseline and Week 52 | 
| Change From Baseline to Week 52 of Vaginal pH. | A pH strip fixed on an Ayre spatula (or equivalent) was applied directly to the lateral wall of the vagina. The change in color of the pH indicator strip was compared to the color chart for pH evaluation. The corresponding pH value (with one decimal) was recorded. Data obtained at Baseline and Week 52 as well as the change from Baseline to Week 52 are presented. | Baseline and Week 52 | 
| Change From Baseline to Week 52 of Self-assessment of VVA Symptom Dyspareunia | The severity of dyspareunia was evaluated by a questionnaire. The severity of dyspareunia recorded as none, mild, moderate or severe was analyzed using the score values of 0, 1, 2 or 3, respectively. Data obtained at Baseline and Week 52 as well as the change from Baseline to Week 52 are presented. | Baseline and Week 52 | 
| Change From Baseline to Week 52 of Self-assessment of VVA Symptom Vaginal Dryness | The severity of vaginal dryness was evaluated by a questionnaire. The severity of vaginal dryness recorded as none, mild, moderate or severe was analyzed using the score values of 0, 1, 2 or 3, respectively. Data obtained at Baseline and Week 52 as well as the change from Baseline to Week 52 are presented. | Baseline and Week 52 | 
| Change From Baseline to Week 52 of Self-assessment of VVA Symptom Irritation/Itching | The severity of irritation/itching was evaluated by a questionnaire. The severity of irritation/itching recorded as none, mild, moderate or severe was analyzed using the score values of 0, 1, 2 or 3, respectively. Data obtained at Baseline and Week 52 as well as the change from Baseline to Week 52 are presented. | Baseline and Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vulvar/Vaginal Atrophy, Atrophic Vaginitis, Dehydroepiandrosterone, DHEA, Prasterone, Vaginorm, Menopause, Intrarosa