DHEA Against Vaginal Atrophy - Safety Study of 12 Months

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 530
• 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, H2X 3J4
      • EndoCeutics site # 34
    • 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
  • District of Columbia
    • Washington, D.C., District of Columbia, United States, 20036
      • EndoCeutics site # 07
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • EndoCeutics site # 45
    • Jacksonville, Florida, United States, 32207
      • EndoCeutics site # 26
    • West Palm Beach, Florida, United States, 33401
      • EndoCeutics site # 41
  • 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
    • Omaha, Nebraska, United States, 68131
      • EndoCeutics site # 24
  • New Jersey
    • Moorestown, New Jersey, United States, 08057
      • EndoCeutics site # 28
    • Neptune City, New Jersey, United States, 07753
      • EndoCeutics site # 50
    • 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
    • Beachwood, Ohio, United States, 44122
      • EndoCeutics site # 33
    • Cleveland, Ohio, United States, 44122
      • EndoCeutics site # 05
    • Cleveland, Ohio, United States, 44124
      • EndoCeutics site # 47
    • 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
  • Washington
    • Renton, Washington, United States, 98055
      • EndoCeutics site # 38

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 (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

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

• Labrie F, Archer DF, Bouchard C, Girard G, Ayotte N, Gallagher JC, Cusan L, Baron M, Blouin F, Waldbaum AS, Koltun W, Portman DJ, Cote I, Lavoie L, Beauregard A, Labrie C, Martel C, Balser J, Moyneur E; Members of the VVA Prasterone Group. Prasterone has parallel beneficial effects on the main symptoms of vulvovaginal atrophy: 52-week open-label study. Maturitas. 2015 May;81(1):46-56. doi: 10.1016/j.maturitas.2015.02.005. Epub 2015 Feb 16.
• Bouchard C, Labrie F, Derogatis L, Girard G, Ayotte N, Gallagher J, Cusan L, Archer DF, Portman D, Lavoie L, Beauregard A, Cote I, Martel C, Vaillancourt M, Balser J, Moyneur E; VVA Prasterone Group. Effect of intravaginal dehydroepiandrosterone (DHEA) on the female sexual function in postmenopausal women: ERC-230 open-label study. Horm Mol Biol Clin Investig. 2016 Mar;25(3):181-90. doi: 10.1515/hmbci-2015-0044.
• Ke Y, Gonthier R, Simard JN, Archer D, Lavoie L, Martel C, Vaillancourt M, Labrie F. Serum steroids remain within the same normal postmenopausal values during 12-month intravaginal 0.50% DHEA. Horm Mol Biol Clin Investig. 2015 Dec;24(3):117-29. doi: 10.1515/hmbci-2015-0035.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): December 1, 2012

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): October 18, 2017
• Last Update Submitted That Met QC Criteria: September 15, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Vulvar/Vaginal Atrophy; Atrophic Vaginitis; Dehydroepiandrosterone; DHEA; Prasterone; Vaginorm; Menopause; Intrarosa
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Dehydroepiandrosterone
• Other Study ID Numbers: ERC-230

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No