Effect of Intravaginal Prasterone on Symptoms of VVA in Women Under Treatment With an Aromatase Inhibitor for Breast Cancer

Effect of Intravaginal Prasterone (DHEA) on Moderate to Severe Symptoms of Vulvovaginal Atrophy Due to Menopause, in Women Under Treatment With an Aromatase Inhibitor for Breast Cancer - (Placebo-Controlled, Double Blind and Randomized Phase III Study)

The purpose of this study is to confirm the efficacy of intravaginal prasterone (DHEA) on moderate to severe (MS) and most bothersome symptoms (MBS) of vulvovaginal atrophy (VVA) due to natural, surgical or treatment-induced menopause, in women with breast cancer who are under treatment with an aromatase inhibitor.

Study Overview

• Status: Withdrawn
• Conditions: Vaginal Atrophy in Breast Cancer Patients
• Intervention / Treatment: Drug: Placebo; Drug: Prasterone (DHEA)

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Main criteria:

1. Natural, surgically- or treatment-induced postmenopausal women (non hysterectomized or hysterectomized) with breast cancer (stage 1 or 2) who is currently under treatment with an aromatase inhibitor and will remain on that treatment for the duration of the study.
2. Women between 30 and 80 years of age
3. Women having ≤5% of superficial cells on vaginal smear at baseline
4. Women having a vaginal pH above 5 at baseline
5. Women who have self-identified moderate or severe symptom(s) of vaginal atrophy

Exclusion Criteria:

Main criteria:

1. Clinically significant metabolic or endocrine disease (including diabetes mellitus) not controlled by medication
2. The administration of any investigational drug within 30 days of screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• 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; Daily administration of one placebo vaginal ovule at bedtime
Experimental: Prasterone; Prasterone (DHEA) vaginal ovule daily for 12 weeks	Drug: Prasterone (DHEA); Daily administration of one prasterone vaginal ovule at bedtime; Other Names: Intrarosa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline to Week 12 in the Percentage of Superficial Cells	12 weeks
Change from Baseline to Week 12 in the Percentage of Parabasal Cells	12 weeks
Change from Baseline to Week 12 in Vaginal pH	12 weeks
Change from Baseline to Week 12 in Moderate/Severe VVA symptom being Most Bothersome (MBS)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline to Week 12 in Moderate/Severe VVA symptom (not most bothersome)		12 weeks
Change from Baseline to Week 12 on arousal/lubrication domain of Female Sexual Function Index (FSFI) questionnaire	Individual domain score will be obtained by adding the scores of the individual questions that comprise the domain and multiplying the sum by the domain factor.	12 weeks
Change from Baseline to Week 12 on subjective arousal domain of FSFI	Individual domain score will be obtained by adding the scores of the individual questions that comprise the domain and multiplying the sum by the domain factor.	12 weeks
Change from Baseline to Week 12 on desire domain of FSFI	Individual domain score will be obtained by adding the scores of the individual questions that comprise the domain and multiplying the sum by the domain factor.	12 weeks
Change from Baseline to Week 12 on satisfaction domain of FSFI	Individual domain score will be obtained by adding the scores of the individual questions that comprise the domain and multiplying the sum by the domain factor.	12 weeks
Change from Baseline to Week 12 on orgasm domain of FSFI	Individual domain score will be obtained by adding the scores of the individual questions that comprise the domain and multiplying the sum by the domain factor.	12 weeks
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions	Vaginal parameter evaluated at gynecological examination by the physician/gynecologist will be graded as corresponding to none, mild, moderate, or severe atrophy.	12 weeks
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness	Vaginal parameter evaluated at gynecological examination by the physician/gynecologist will be graded as corresponding to none, mild, moderate, or severe atrophy.	12 weeks
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity	Vaginal parameter evaluated at gynecological examination by the physician/gynecologist will be graded as corresponding to none, mild, moderate, or severe atrophy.	12 weeks
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color	Vaginal parameter evaluated at gynecological examination by the physician/gynecologist will be graded as corresponding to none, mild, moderate, or severe atrophy.	12 weeks

Collaborators and Investigators

• Sponsor: EndoCeutics Inc.
• Collaborators: AMAG Pharmaceuticals, Inc.
• Investigators: Study Chair: Claude Labrie, M.D., Ph.D., Endoceutics, Inc., Quebec, Canada; Principal Investigator: David F Archer, M.D., Jones Institute, Norfolk VA 23507; Principal Investigator: Sheryl Kingsberg, Ph.D., MacDonald Women's Hospital, Cleveland, OH 44106 USA

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• Labrie F, Archer DF, Martel C, Vaillancourt M, Montesino M. Combined data of intravaginal prasterone against vulvovaginal atrophy of menopause. Menopause. 2017 Nov;24(11):1246-1256. doi: 10.1097/GME.0000000000000910.

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2018
• Primary Completion (Actual): December 5, 2019
• Study Completion (Actual): December 5, 2019

Study Registration Dates

• First Submitted: November 7, 2018
• First Submitted That Met QC Criteria: November 10, 2018
• First Posted (Actual): November 14, 2018

Study Record Updates

• Last Update Posted (Actual): July 31, 2020
• Last Update Submitted That Met QC Criteria: July 29, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Breast cancer; DHEA; Prasterone; Intrarosa; Vaginal atrophy; Aromatase inhibitor; Atrophic vaginitis; Vulvovaginal atrophy (VVA)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Pathological Conditions, Anatomical; Breast Neoplasms; Atrophy; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Dehydroepiandrosterone
• Other Study ID Numbers: ERC-260

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No