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

• ClinicalTrials.gov Identifier: NCT03740945
• Recruitment Status: Withdrawn
• First Posted: November 14, 2018
• Last Update Posted: July 31, 2020
• Sponsor: EndoCeutics Inc.
• Collaborator: AMAG Pharmaceuticals, Inc.
• Information provided by (Responsible Party): EndoCeutics Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Vaginal Atrophy in Breast Cancer Patients	Drug: Placebo; Drug: Prasterone (DHEA)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: November 6, 2018
• Actual Primary Completion Date: December 5, 2019
• Actual Study Completion Date: December 5, 2019

Arms and Interventions

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 Name: Intrarosa

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline to Week 12 in the Percentage of Superficial Cells [ Time Frame: 12 weeks ]
2. Change from Baseline to Week 12 in the Percentage of Parabasal Cells [ Time Frame: 12 weeks ]
3. Change from Baseline to Week 12 in Vaginal pH [ Time Frame: 12 weeks ]
4. Change from Baseline to Week 12 in Moderate/Severe VVA symptom being Most Bothersome (MBS) [ Time Frame: 12 weeks ]

Secondary Outcome Measures :

1. Change from Baseline to Week 12 in Moderate/Severe VVA symptom (not most bothersome) [ Time Frame: 12 weeks ]
2. Change from Baseline to Week 12 on arousal/lubrication domain of Female Sexual Function Index (FSFI) questionnaire [ Time Frame: 12 weeks ]
   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.
3. Change from Baseline to Week 12 on subjective arousal domain of FSFI [ Time Frame: 12 weeks ]
   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.
4. Change from Baseline to Week 12 on desire domain of FSFI [ Time Frame: 12 weeks ]
   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.
5. Change from Baseline to Week 12 on satisfaction domain of FSFI [ Time Frame: 12 weeks ]
   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.
6. Change from Baseline to Week 12 on orgasm domain of FSFI [ Time Frame: 12 weeks ]
   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.
7. Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions [ Time Frame: 12 weeks ]
   Vaginal parameter evaluated at gynecological examination by the physician/gynecologist will be graded as corresponding to none, mild, moderate, or severe atrophy.
8. Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness [ Time Frame: 12 weeks ]
   Vaginal parameter evaluated at gynecological examination by the physician/gynecologist will be graded as corresponding to none, mild, moderate, or severe atrophy.
9. Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity [ Time Frame: 12 weeks ]
   Vaginal parameter evaluated at gynecological examination by the physician/gynecologist will be graded as corresponding to none, mild, moderate, or severe atrophy.
10. Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color [ Time Frame: 12 weeks ]
    Vaginal parameter evaluated at gynecological examination by the physician/gynecologist will be graded as corresponding to none, mild, moderate, or severe atrophy.

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Sponsors and Collaborators

EndoCeutics Inc.

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

More Information

Publications of Results:

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, Côté I, Parent J, Lavoie L, Beauregard A, Martel C, Vaillancourt M, Balser J, Moyneur É; 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, Côté 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, Côté I, Parent J, Lavoie L, Beauregard A, Martel C, Vaillancourt M, Balser J, Moyneur É; 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 É; 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, Côté 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, Côté 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.

• Responsible Party: EndoCeutics Inc.
• ClinicalTrials.gov Identifier: NCT03740945
• Other Study ID Numbers: ERC-260
• First Posted: November 14, 2018
• Last Update Posted: July 31, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by EndoCeutics Inc.:

Vulvovaginal atrophy (VVA); Vaginal atrophy; Atrophic vaginitis; Prasterone; DHEA; Intrarosa; Breast cancer; Aromatase inhibitor

Additional relevant MeSH terms:

Breast Neoplasms; Atrophy; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Pathological Conditions, Anatomical; Dehydroepiandrosterone; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs