Intravaginal Prasterone (DHEA) Against Vulvovaginal Atrophy Associated With Menopause

• Placebo (Drug)
• Prasterone (DHEA) (Drug)

Primary outcomes

• Change From Baseline to Week 12 in Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear [Baseline and Week 12]: 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.
• Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear [Baseline and Week 12]: 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.
• Change From Baseline to Week 12 in Vaginal pH [Baseline and Week 12]: 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.
• Change From Baseline to Week 12 in Severity of the Most Bothersome Symptom of Dyspareunia [Baseline and Week 12]: 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.

Secondary outcomes

• Change From Baseline to Week 12 in Severity of Vaginal Dryness [Baseline and Week 12]: 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.
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions [Baseline and Week 12]: 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.
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity [Baseline and Week 12]: 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.
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness [Baseline and Week 12]: 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.
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color [Baseline and Week 12]: 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.

Sex: Female, ages: 40 Years to 80 Years

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

Participant flow

Outcome results

• Change From Baseline to Week 12 in Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear (Primary), Mean, Percentage of superficial cells: Placebo 1.04 +/- 0.11; 0.50% Prasterone (DHEA) 1.02 +/- 0.08
• Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear (Primary), Mean, Percentage of parabasal cells: Placebo 51.66 +/- 3.00; 0.50% Prasterone (DHEA) 54.25 +/- 2.14
• Change From Baseline to Week 12 in Vaginal pH (Primary), Mean, units on a scale: Placebo 6.32 +/- 0.05; 0.50% Prasterone (DHEA) 6.34 +/- 0.04
• Change From Baseline to Week 12 in Severity of the Most Bothersome Symptom of Dyspareunia (Primary), Mean, units on a scale: Placebo 2.56 +/- 0.04; 0.50% Prasterone (DHEA) 2.54 +/- 0.03
• Change From Baseline to Week 12 in Severity of Vaginal Dryness (Secondary), Mean, units on a scale: Placebo 2.30 +/- 0.04; 0.50% Prasterone (DHEA) 2.30 +/- 0.03
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions (Secondary), Mean, units on a scale: Placebo 2.63 +/- 0.05; 0.50% Prasterone (DHEA) 2.70 +/- 0.04
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity (Secondary), Mean, units on a scale: Placebo 2.43 +/- 0.06; 0.50% Prasterone (DHEA) 2.45 +/- 0.05
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness (Secondary), Mean, units on a scale: Placebo 2.76 +/- 0.05; 0.50% Prasterone (DHEA) 2.83 +/- 0.03
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color (Secondary), Mean, units on a scale: Placebo 2.67 +/- 0.05; 0.50% Prasterone (DHEA) 2.75 +/- 0.03

Adverse events

Time frame: From Baseline to Week 12 (+ 30-day follow-up period after last dose)

Serious adverse events by term

Other adverse events by term

• Results publication: 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. PMID 26291918
• Results publication: 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. PMID 26597311
• Results publication: 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. PMID 26517756
• Results publication: 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. PMID 26731686
• Results publication: 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. PMID 26972555
• Results publication: 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. PMID 26634942

• Fernand Labrie, M.D., Ph.D., Study chair, EndoCeutics Inc.
• David F Archer, M.D., Principal investigator, Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA