Topical DHEA Against Vaginal Atrophy

Topical DHEA Against Vaginal Atrophy (3-Month Placebo-Controlled Double-Blind Randomized Phase III Study)

The purpose of this study is to determine the dose-response of vaginal mucosa parameters to the local action of DHEA (Dehydroepiandrosterone) in postmenopausal women suffering from vaginal atrophy.

Study Overview

• Status: Completed
• Conditions: Vaginal Atrophy
• Intervention / Treatment: Drug: Placebo; Drug: DHEA (0.25%); Drug: DHEA (0.5%); Drug: DHEA (1.0%)

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1S 2L6
    • EndoCeutics site # 02
  • Quebec, Canada, G1V 4G2
    • EndoCeutics site # 01
  • Quebec
    • Montreal, Quebec, Canada, H1T 1P6
      • EndoCeutics site # 10
    • Montreal, Quebec, Canada, H3A 1A1
      • EndoCeutics site # 09
    • Shawinigan, Quebec, Canada, G9N 2H6
      • EndoCeutics site # 08
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • EndoCeutics site # 11
• United States
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • EndoCeutics site # 05
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • EndoCeutics site # 03

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal women (non hysterectomized or hysterectomized)
• Women between 40 and 75 years of age
• Willing to participate in the study and sign an informed consent
• Women having a low maturation index (no greater part of guidance than 5% of superficial cells on vaginal smear)
• Women having a vaginal pH above 5
• Women who have self-identified at least one moderate to severe symptoms of vulvovaginal atrophy

Exclusion Criteria:

• Undiagnosed abnormal genital bleeding
• Hypertension equal to or above 160/95 mm Hg or not controlled by standard therapy
• The administration of any investigational drug within 30 days of screening visit
• Endometrial hyperplasia at biopsy performed at screening or endometrial cancer
• Use of estrogens/progestins products (vaginal, oral, pellet, transdermal, etc) in the 4 weeks to 6 months (depending on the product used) prior study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo vaginal suppository containing 0.0% (0 mg) DHEA; daily dosing with one suppository for 12 weeks.; Other Names: Prasterone, Dehydroepiandrosterone
Experimental: 0.25% DHEA	Drug: DHEA (0.25%); Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.; Other Names: Prasterone, Dehydroepiandrosterone
Experimental: 0.5% DHEA	Drug: DHEA (0.5%); Vaginal suppository containing 0.5% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.; Other Names: Prasterone, Dehydroepiandrosterone
Experimental: 1.0% DHEA	Drug: DHEA (1.0%); Vaginal suppository containing 1.0% (13 mg) DHEA; daily dosing with one suppository for 12 weeks.; Other Names: Prasterone, Dehydroepiandrosterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Co-primary Endpoint: Change From Baseline to Week 12 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 12 as well as the change from Baseline to Week 12 are presented.	Baseline and Week 12
Co-primary Endpoint: Change From Baseline to Week 12 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 12 as well as the change from Baseline to Week 12 are presented.	Baseline and Week 12
Co-primary Endpoint: Change From Baseline to Week 12 of Vaginal pH.	A pH strip was applied directly to the lateral wall of the vagina using forceps. 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 12 as well as the change from Baseline to Week 12 are presented.	Baseline and Week 12
Co-primary Endpoint: Change From Baseline to Week 12 of Self-assessment of the Most Bothersome 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 12 as well as the change from Baseline to Week 12 are presented.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 of Vaginal Secretions	To evaluate the aspect of the vaginal mucosa and the local tolerance to DHEA suppository, the vaginal secretions (one of the four main signs of vaginal atrophy) evaluated by the physician/gynecologist as corresponding to none, mild, moderate, or severe atrophy were analyzed using the score values of 1, 2, 3 and 4, respectively. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.	Baseline and Week 12
Change From Baseline to Week 12 of Vaginal Epithelial Integrity	To evaluate the aspect of the vaginal mucosa and the local tolerance to DHEA suppository, the vaginal epithelial integrity (one of the four main signs of vaginal atrophy) evaluated by the physician/gynecologist as corresponding to none, mild, moderate, or severe atrophy was analyzed using the score values of 1, 2, 3 and 4, respectively. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.	Baseline and Week 12
Change From Baseline to Week 12 of Vaginal Epithelial Surface Thickness	To evaluate the aspect of the vaginal mucosa and the local tolerance to DHEA suppository, the vaginal epithelial surface thickness(one of the four main signs of vaginal atrophy) evaluated by the physician/gynecologist as corresponding to none, mild, moderate, or severe atrophy was analyzed using the score values of 1, 2, 3 and 4, respectively. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.	Baseline and Week 12
Change From Baseline to Week 12 of Vaginal Color	To evaluate the aspect of the vaginal mucosa and the local tolerance to DHEA suppository, the vaginal color (one of the four main signs of vaginal atrophy) evaluated by the physician/gynecologist as corresponding to none, mild, moderate, or severe atrophy was analyzed using the score values of 1, 2, 3 and 4, respectively. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.	Baseline and Week 12

Collaborators and Investigators

• Sponsor: EndoCeutics Inc.
• Investigators: Principal Investigator: David F Archer, MD, Clinical Research Center, Eastern Virginia Medical Scholl, Norfolk, VA

Publications and helpful links

General Publications

• Portman DJ, Labrie F, Archer DF, Bouchard C, Cusan L, Girard G, Ayotte N, Koltun W, Blouin F, Young D, Wade A, Martel C, Dube R; other participating members of VVA Prasterone Group. Lack of effect of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women. Menopause. 2015 Dec;22(12):1289-95. doi: 10.1097/GME.0000000000000470.
• Martel C, Labrie F, Archer DF, Ke Y, Gonthier R, Simard JN, Lavoie L, Vaillancourt M, Montesino M, Balser J, Moyneur E; other participating members of the Prasterone Clinical Research Group. Serum steroid concentrations remain within normal postmenopausal values in women receiving daily 6.5mg intravaginal prasterone for 12 weeks. J Steroid Biochem Mol Biol. 2016 May;159:142-53. doi: 10.1016/j.jsbmb.2016.03.016. Epub 2016 Mar 10.
• Labrie F, Archer D, Bouchard C, Fortier M, Cusan L, Gomez JL, Girard G, Baron M, Ayotte N, Moreau M, Dube R, Cote I, Labrie C, Lavoie L, Berube R, Belanger P, Berger L, Gilbert L, Martel C, Balser J. Serum steroid levels during 12-week intravaginal dehydroepiandrosterone administration. Menopause. 2009 Sep-Oct;16(5):897-906. doi: 10.1097/gme.0b013e31819e8930.
• Labrie F, Archer D, Bouchard C, Fortier M, Cusan L, Gomez JL, Girard G, Baron M, Ayotte N, Moreau M, Dube R, Cote I, Labrie C, Lavoie L, Berger L, Gilbert L, Martel C, Balser J. Intravaginal dehydroepiandrosterone (Prasterone), a physiological and highly efficient treatment of vaginal atrophy. Menopause. 2009 Sep-Oct;16(5):907-22. doi: 10.1097/gme.0b013e31819e8e2d.
• Labrie F, Archer D, Bouchard C, Fortier M, Cusan L, Gomez JL, Girard G, Baron M, Ayotte N, Moreau M, Dube R, Cote I, Labrie C, Lavoie L, Berger L, Gilbert L, Martel C, Balser J. Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women. Menopause. 2009 Sep-Oct;16(5):923-31. doi: 10.1097/gme.0b013e31819e85c6.
• Labrie F, Archer D, Bouchard C, Fortier M, Cusan L, Gomez JL, Girard G, Baron M, Ayotte N, Moreau M, Dube R, Cote I, Labrie C, Lavoie L, Berger L, Martel C, Balser J. High internal consistency and efficacy of intravaginal DHEA for vaginal atrophy. Gynecol Endocrinol. 2010 Jul;26(7):524-32. doi: 10.3109/09513590903511547.
• Labrie F, Archer DF, Bouchard C, Fortier M, Cusan L, Gomez JL, Girard G, Baron M, Ayotte N, Moreau M, Dube R, Cote I, Labrie C, Lavoie L, Berger L, Gilbert L, Martel C, Balser J. Intravaginal dehydroepiandrosterone (prasterone), a highly efficient treatment of dyspareunia. Climacteric. 2011 Apr;14(2):282-8. doi: 10.3109/13697137.2010.535226. Epub 2011 Jan 18.
• Labrie F, Archer D, Bouchard C, Fortier M, Cusan L, Gomez JL, Girard G, Baron M, Ayotte N, Moreau M, Dube R, Cote I, Labrie C, Lavoie L, Gilbert L, Martel C, Balser J. Lack of influence of dyspareunia on the beneficial effect of intravaginal prasterone (dehydroepiandrosterone, DHEA) on sexual dysfunction in postmenopausal women. J Sex Med. 2014 Jul;11(7):1766-85. doi: 10.1111/jsm.12517. Epub 2014 Apr 28.
• Labrie F. Intravaginal DHEA, by a strictly local action, exerts beneficial effects on both vaginal atrophy symptoms and sexual dysfunction. Horm Mol Biol Clin Investig. 2010 Dec 1;4(1):499-507. doi: 10.1515/HMBCI.2010.064.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: May 1, 2013
• First Submitted That Met QC Criteria: May 1, 2013
• First Posted (Estimate): May 3, 2013

Study Record Updates

• Last Update Posted (Actual): August 29, 2017
• Last Update Submitted That Met QC Criteria: July 28, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Atrophic Vaginitis; Dehydroepiandrosterone; DHEA; Prasterone; Vaginorm; Menopause; Intrarosa; Vulvar/vaginal atrophy
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Dehydroepiandrosterone
• Other Study ID Numbers: ERC-210