Intravaginal Prasterone (DHEA) Against Vulvovaginal Atrophy Associated With Menopause

The purpose of this study is to confirm the efficacy of intravaginal prasterone (DHEA) on symptoms of vulvovaginal atrophy due to menopause and to collect further data on subjects exposed to intravaginal DHEA in order to meet the ICH E1 guideline requirements.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 558
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Burlington, Ontario, Canada, L7R 4B8
      • EndoCeutics site # 85
    • Corunna, Ontario, Canada, N0N1G0
      • EndoCeutics site # 69
    • Sarnia, Ontario, Canada, N7T 4X3
      • EndoCeutics site # 68
    • Waterloo, Ontario, Canada, N2J 1C4
      • EndoCeutics site # 73
  • Quebec
    • Drummondville, Quebec, Canada, J2B 7T1
      • EndoCeutics site # 04
    • Montreal, Quebec, Canada, H4N 3C5
      • EndoCeutics site # 12
    • Pointe-Claire, Quebec, Canada, H9R 4S3
      • EndoCeutics site # 79
    • Quebec City, Quebec, Canada, G1S 2L6
      • EndoCeutics site # 02
    • Quebec City, Quebec, Canada, G1V 2L9
      • EndoCeutics site # 01
    • Quebec City, Quebec, Canada, G1W 4R4
      • EndoCeutics site # 77
    • Quebec City, Quebec, Canada, G3K 2P8
      • EndoCeutics site # 78
    • Sherbrooke, Quebec, Canada, J1J 2G2
      • EndoCeutics site # 74
    • St-Romuald, Quebec, Canada, G6W 5M6
      • EndoCeutics site # 18
    • Victoriaville, Quebec, Canada, G6P 6P6
      • EndoCeutics site # 67
• 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, 92103
      • EndoCeutics site # 83
  • Colorado
    • Denver, Colorado, United States, 80209
      • EndoCeutics site # 36
    • Denver, Colorado, United States, 80220
      • EndoCeutics site # 52
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • EndoCeutics site # 45
    • Lake Worth, Florida, United States, 33461
      • EndoCeutics site # 60
    • North Miami, Florida, United States, 33161
      • EndoCeutics site # 54
    • West Palm Beach, Florida, United States, 33409
      • EndoCeutics site # 80
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • EndoCeutics site # 23
  • Kansas
    • Wichita, Kansas, United States, 67226
      • EndoCeutics site # 55
  • Kentucky
    • Louisville, Kentucky, United States, 40291
      • EndoCeutics site # 86
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • EndoCeutics site # 27
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • EndoCeutics site # 87
    • Plainsboro, New Jersey, United States, 08536
      • EndoCeutics site # 81
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • EndoCeutics site # 05
    • Columbus, Ohio, United States, 43213
      • EndoCeutics site # 15
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114-1029
      • EndoCeutics site # 75
  • Texas
    • Corpus Christi, Texas, United States, 78414
      • EndoCeutics site # 84
    • Houston, Texas, United States, 77030
      • EndoCeutics site # 82
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • EndoCeutics site # 03
  • Washington
    • Seattle, Washington, United States, 98105
      • EndoCeutics site # 76

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Main criteria:

• Postmenopausal women (hysterectomized or not)
• Women between 40 and 80 years of age
• Women having ≤5% of superficial cells on vaginal smear at baseline
• Women having a vaginal pH above 5 at baseline
• Women who have self-identified moderate or severe symptom(s) of vaginal atrophy
• Willing to participate in the study and sign an informed consent

Exclusion Criteria:

Main criteria:

• Previous enrollment in EndoCeutics studies performed with intravaginal DHEA
• Previous diagnosis of cancer, except skin cancer (non melanoma)
• Clinically significant metabolic or endocrine disease (including diabetes mellitus) not controlled by medication
• The administration of any investigational drug within 30 days of screening visit
• Clinically significant abnormal serum biochemistry, urinalysis or hematology

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo vaginal ovule daily for 12 weeks	Drug: Placebo
EXPERIMENTAL: Prasterone; Prasterone (DHEA) vaginal ovule daily for 12 weeks	Drug: Prasterone (DHEA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear	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
Change From Baseline to Week 12 in Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear	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
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 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 Atrophy as Evaluated From Vaginal Secretions	To evaluate the aspect of the mucosa and the local tolerance to prasterone ovules, 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 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity	To evaluate the aspect of the mucosa and the local tolerance to prasterone ovules, 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 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness	To evaluate the aspect of the mucosa and the local tolerance to prasterone ovules, 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 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color	To evaluate the aspect of the mucosa and the local tolerance to prasterone ovules, 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
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

Collaborators and Investigators

• Sponsor: EndoCeutics Inc.
• Investigators: Study Chair: Fernand Labrie, M.D., Ph.D., EndoCeutics Inc.; Principal Investigator: David F Archer, M.D., Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA

Publications and helpful links

General Publications

• Ke Y, Labrie F, Gonthier R, Simard JN, Bergeron D, Martel C, Vaillancourt M, Montesino M, Lavoie L, Archer DF, Balser J, Moyneur E; other participating Members of the Prasterone Clinical Research Group. Serum levels of sex steroids and metabolites following 12 weeks of intravaginal 0.50% DHEA administration. J Steroid Biochem Mol Biol. 2015 Nov;154:186-96. doi: 10.1016/j.jsbmb.2015.08.016. Epub 2015 Aug 17.
• Labrie F, Derogatis L, Archer DF, Koltun W, Vachon A, Young D, Frenette L, Portman D, Montesino M, Cote I, Parent J, Lavoie L, Beauregard A, Martel C, Vaillancourt M, Balser J, Moyneur E; Members of the VVA Prasterone Research Group. Effect of Intravaginal Prasterone on Sexual Dysfunction in Postmenopausal Women with Vulvovaginal Atrophy. J Sex Med. 2015 Dec;12(12):2401-12. doi: 10.1111/jsm.13045. Epub 2015 Nov 23.
• Labrie F, Montesino M, Archer DF, Lavoie L, Beauregard A, Cote I, Martel C, Vaillancourt M, Balser J, Moyneur E; other participating Members of the Prasterone Clinical Research Group. Influence of treatment of vulvovaginal atrophy with intravaginal prasterone on the male partner. Climacteric. 2015;18(6):817-25. doi: 10.3109/13697137.2015.1077508. Epub 2015 Oct 30.
• Labrie F, Archer DF, Koltun W, Vachon A, Young D, Frenette L, Portman D, Montesino M, Cote I, Parent J, Lavoie L, Beauregard A, Martel C, Vaillancourt M, Balser J, Moyneur E; VVA Prasterone Research Group. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2016 Mar;23(3):243-56. doi: 10.1097/GME.0000000000000571.
• 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.
• Montesino M, Labrie F, Archer DF, Zerhouni J, Cote I, Lavoie L, Beauregard A, Martel C, Vaillancourt M, Moyneur E, Balser J. Evaluation of the acceptability of intravaginal prasterone ovule administration using an applicator. Gynecol Endocrinol. 2016;32(3):240-5. doi: 10.3109/09513590.2015.1110140. Epub 2016 Jan 6.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (ACTUAL): January 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: December 9, 2013
• First Submitted That Met QC Criteria: December 11, 2013
• First Posted (ESTIMATE): December 17, 2013

Study Record Updates

• Last Update Posted (ACTUAL): June 1, 2017
• Last Update Submitted That Met QC Criteria: May 30, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: DHEA; Intrarosa; Vaginal atrophy; prasterone; Atrophic vaginitis; Vulvovaginal atrophy (VVA)
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Dehydroepiandrosterone
• Other Study ID Numbers: ERC-238