DHEA Against Vaginal Atrophy - 3-Month Efficacy Study

DHEA Against Vaginal Atrophy (Placebo-controlled, Double-blind and Randomized Phase III Study of 3-month Intravaginal DHEA)

The purpose of this Phase III trial is to confirm the efficacy of intravaginal dehydroepiandrosterone (DHEA) in postmenopausal women with vaginal atrophy.

Study Overview

• Status: Completed
• Conditions: Vaginal Atrophy
• Intervention / Treatment: Drug: Placebo; Drug: DHEA; Drug: DHEA

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4L7
      • EndoCeutics site # 13
  • New Brunswick
    • Bathurst, New Brunswick, Canada, E2A 4X7
      • EndoCeutics site # 06
  • Quebec
    • Drummondville, Quebec, Canada, J2B 7T1
      • EndoCeutics site # 04
    • Montreal, Quebec, Canada, H4N 3C5
      • EndoCeutics site # 12
    • Quebec City, Quebec, Canada, G1S 2L6
      • EndoCeutics site # 02
    • Quebec City, Quebec, Canada, G1V 2L9
      • EndoCeutics site # 01
    • Shawinigan, Quebec, Canada, G9N 2H6
      • EndoCeutics site # 08
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • EndoCeutics site # 11
    • St-Romuald, Quebec, Canada, G6W 5M6
      • EndoCeutics site # 18
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36117
      • EndoCeutics site # 39
  • Arizona
    • Tucson, Arizona, United States, 85712
      • EndoCeutics site # 14
  • California
    • Sacramento, California, United States, 95821
      • EndoCeutics site # 21
    • San Diego, California, United States, 92108
      • EndoCeutics site # 30
    • San Diego, California, United States, 92120
      • EndoCeutics site # 17
  • Colorado
    • Denver, Colorado, United States, 80218
      • EndoCeutics site # 36
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • EndoCeutics site # 42
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • EndoCeutics site # 45
    • Jacksonville, Florida, United States, 32207
      • EndoCeutics site # 26
  • Georgia
    • Sandy Springs, Georgia, United States, 30328
      • EndoCeutics site # 23
  • Idaho
    • Meridian, Idaho, United States, 83642
      • EndoCeutics site # 10
  • Maryland
    • Baltimore, Maryland, United States, 21285-6815
      • EndoCeutics site # 27
  • Michigan
    • Kalamazoo, Michigan, United States, 49009
      • EndoCeutics site # 22
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • EndoCeutics site # 25
  • New Jersey
    • Moorestown, New Jersey, United States, 08057
      • EndoCeutics site # 28
    • New Brunswick, New Jersey, United States, 08901
      • EndoCeutics site # 44
  • New York
    • New York, New York, United States, 10016
      • EndoCeutics site # 19
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • EndoCeutics site # 16
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • EndoCeutics site # 05
    • Columbus, Ohio, United States, 43213
      • EndoCeutics site # 15
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15206
      • EndoCeutics site # 35
  • Utah
    • West Jordan, Utah, United States, 84088
      • EndoCeutics site # 09
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • EndoCeutics site # 31
    • Norfolk, Virginia, United States, 23507
      • EndoCeutics site # 03

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Main Inclusion Criteria:

• Postmenopausal women (hysterectomized or 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.
• For non-hysterectomized women, willing to have endometrial biopsy at screening and end of study.

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo vaginal suppository
Experimental: 0.25% DHEA	Drug: DHEA; Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.; Other Names: Prasterone, Dehydroepiandrosterone; Drug: DHEA; Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.; Other Names: Prasterone, Dehydroepiandrosterone
Experimental: 0.5% DHEA	Drug: DHEA; Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.; Other Names: Prasterone, Dehydroepiandrosterone; Drug: DHEA; Vaginal suppository containing 0.50% (6.5 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
Change From Baseline to Week 12 in 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 12 as well as the change from Baseline to Week 12 are presented.	Baseline and Week 12
Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear	The percentage of parabasal cell 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 the 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
Change From Baseline to Week 12 in Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear	The percentage of superficial cell 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 the 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
Change From Baseline to Week 12 in Severity of the Most Bothersome Symptom of Dyspareunia	The severity of dyspareunia was evaluated by a questionnaire filled out by women. 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 in Severity of Vaginal Dryness	The severity of vaginal dryness was evaluated by a questionnaire filled out by women. 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 12 as well as the change from Baseline to Week 12 are presented.	Baseline and Week 12
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions	To evaluate the aspect of the mucosa and the local tolerance to DHEA suppositories, 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 then 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 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity	To evaluate the aspect of the mucosa and the local tolerance to DHEA suppositories, 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 then 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 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness	To evaluate the aspect of the mucosa and the local tolerance to DHEA suppositories, 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 then 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 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color	To evaluate the aspect of the mucosa and the local tolerance to DHEA suppositories, 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 then analyzed using the 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 School, 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.
• Archer DF, Labrie F, Bouchard C, Portman DJ, Koltun W, Cusan L, Labrie C, Cote I, Lavoie L, Martel C, Balser J; VVA Prasterone Group. Treatment of pain at sexual activity (dyspareunia) with intravaginal dehydroepiandrosterone (prasterone). Menopause. 2015 Sep;22(9):950-63. doi: 10.1097/GME.0000000000000428.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: December 3, 2010
• First Submitted That Met QC Criteria: December 7, 2010
• First Posted (Estimate): December 8, 2010

Study Record Updates

• Last Update Posted (Actual): June 26, 2017
• Last Update Submitted That Met QC Criteria: May 31, 2017
• Last Verified: May 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-231