Trial Outcomes & Findings for Intravaginal Prasterone (DHEA) Against Vulvovaginal Atrophy Associated With Menopause (NCT NCT02013544)

NCT ID: NCT02013544

Last Updated: 2017-06-01

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 558 participants
• Primary outcome timeframe: Baseline and Week 12
• Results posted on: 2017-06-01

Participant Flow

A total of 1226 subjects were screened at 38 medical/research sites located in the US (24 centers) and Canada (14 centers) and 558 subjects were randomized. The first subject first visit was on 11-FEB-2014 and the last subject last visit was on 06-JAN-2015.

Participant milestones

Measure	Placebo Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks	0.50% Prasterone (DHEA) Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks.
Overall Study STARTED	182	376
Overall Study Safety Population	180	374
Overall Study ITT Population	157	325
Overall Study COMPLETED	171	356
Overall Study NOT COMPLETED	11	20

Reasons for withdrawal

Measure	Placebo Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks	0.50% Prasterone (DHEA) Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks.
Overall Study Adverse Event	5	5
Overall Study Lost to Follow-up	2	3
Overall Study Withdrawal by Subject	2	8
Overall Study Physician Decision	0	1
Overall Study Entry criteria not met/non-compliance	2	3

Baseline Characteristics

Intravaginal Prasterone (DHEA) Against Vulvovaginal Atrophy Associated With Menopause

Baseline characteristics by cohort

Measure	Placebo n=180 Participants Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks.	0.50% Prasterone (DHEA) n=374 Participants Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks.	Total n=554 Participants Total of all reporting groups
Age, Continuous	59.55 years STANDARD_DEVIATION 5.75 • n=93 Participants	59.51 years STANDARD_DEVIATION 6.78 • n=4 Participants	59.53 years STANDARD_DEVIATION 6.46 • n=27 Participants
Sex/Gender, Customized Female	180 Participants n=93 Participants	374 Participants n=4 Participants	554 Participants n=27 Participants
Race/Ethnicity, Customized White Caucasian	163 Participants n=93 Participants	338 Participants n=4 Participants	501 Participants n=27 Participants
Race/Ethnicity, Customized Black or African American	13 Participants n=93 Participants	28 Participants n=4 Participants	41 Participants n=27 Participants
Race/Ethnicity, Customized Asian	2 Participants n=93 Participants	4 Participants n=4 Participants	6 Participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Native hawaiian or Other Pacific Islander	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Other	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Efficacy analyses were performed primarily on the Intent to Treat (ITT) population defined as all subjects who have received at least one dose of study drug with a baseline (Day 1) evaluation meeting the study entry criteria.

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.

Outcome measures

Measure	Placebo n=157 Participants Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks.	0.50% Prasterone (DHEA) n=325 Participants Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks.
Change From Baseline to Week 12 in Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear Baseline	1.04 Percentage of superficial cells Standard Error 0.11	1.02 Percentage of superficial cells Standard Error 0.08
Change From Baseline to Week 12 in Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear Week 12	2.78 Percentage of superficial cells Standard Error 0.27	11.22 Percentage of superficial cells Standard Error 0.56
Change From Baseline to Week 12 in Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear Change from Baseline to Week 12	1.75 Percentage of superficial cells Standard Error 0.27	10.20 Percentage of superficial cells Standard Error 0.57

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Efficacy analyses were performed primarily on the Intent to Treat (ITT) population defined as all subjects who have received at least one dose of study drug with a baseline (Day 1) evaluation meeting the study entry criteria.

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.

Outcome measures

Measure	Placebo n=157 Participants Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks.	0.50% Prasterone (DHEA) n=325 Participants Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks.
Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear Baseline	51.66 Percentage of parabasal cells Standard Error 3.00	54.25 Percentage of parabasal cells Standard Error 2.14
Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear Week 12	39.68 Percentage of parabasal cells Standard Error 2.68	12.74 Percentage of parabasal cells Standard Error 1.02
Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear Change from Baseline to Week 12	-11.98 Percentage of parabasal cells Standard Error 2.36	-41.51 Percentage of parabasal cells Standard Error 2.01

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Efficacy analyses were performed primarily on the Intent to Treat (ITT) population defined as all subjects who have received at least one dose of study drug with a baseline (Day 1) evaluation meeting the study entry criteria.

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.

Outcome measures

Measure	Placebo n=157 Participants Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks.	0.50% Prasterone (DHEA) n=325 Participants Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks.
Change From Baseline to Week 12 in Vaginal pH Baseline	6.32 units on a scale Standard Error 0.05	6.34 units on a scale Standard Error 0.04
Change From Baseline to Week 12 in Vaginal pH Week 12	6.05 units on a scale Standard Error 0.07	5.39 units on a scale Standard Error 0.05
Change From Baseline to Week 12 in Vaginal pH Change from Baseline to Week 12	-0.27 units on a scale Standard Error 0.06	-0.94 units on a scale Standard Error 0.05

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Efficacy analyses were performed primarily on the Intent to Treat (ITT) population defined as all subjects who have received at least one dose of study drug with a baseline (Day 1) evaluation meeting the study entry criteria.

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.

Outcome measures

Measure	Placebo n=157 Participants Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks.	0.50% Prasterone (DHEA) n=325 Participants Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks.
Change From Baseline to Week 12 in Severity of the Most Bothersome Symptom of Dyspareunia Week 12	1.50 units on a scale Standard Error 0.08	1.13 units on a scale Standard Error 0.05
Change From Baseline to Week 12 in Severity of the Most Bothersome Symptom of Dyspareunia Baseline	2.56 units on a scale Standard Error 0.04	2.54 units on a scale Standard Error 0.03
Change From Baseline to Week 12 in Severity of the Most Bothersome Symptom of Dyspareunia Change from Baseline to Week 12	-1.06 units on a scale Standard Error 0.08	-1.42 units on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Efficacy analyses on vaginal dryness were performed on a sub-group of the Intent to Treat (ITT) population (defined as all subjects who have received at least one dose of study drug with a baseline (Day 1) evaluation meeting the study entry criteria) who had self-identified moderate to severe vaginal dryness at Baseline.

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.

Outcome measures

Measure	Placebo n=132 Participants Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks.	0.50% Prasterone (DHEA) n=273 Participants Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks.
Change From Baseline to Week 12 in Severity of Vaginal Dryness Change from Baseline to Week 12	-1.17 units on a scale Standard Error 0.09	-1.44 units on a scale Standard Error 0.06
Change From Baseline to Week 12 in Severity of Vaginal Dryness Baseline	2.30 units on a scale Standard Error 0.04	2.30 units on a scale Standard Error 0.03
Change From Baseline to Week 12 in Severity of Vaginal Dryness Week 12	1.13 units on a scale Standard Error 0.08	0.86 units on a scale Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Efficacy analyses were performed primarily on the Intent to Treat (ITT) population defined as all subjects who have received at least one dose of study drug with a baseline (Day 1) evaluation meeting the study entry criteria.

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.

Outcome measures

Measure	Placebo n=157 Participants Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks.	0.50% Prasterone (DHEA) n=325 Participants Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks.
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions Baseline	2.63 units on a scale Standard Error 0.05	2.70 units on a scale Standard Error 0.04
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions Week 12	2.24 units on a scale Standard Error 0.06	1.97 units on a scale Standard Error 0.04
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions Change from Baseline to Week 12	-0.39 units on a scale Standard Error 0.06	-0.73 units on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Efficacy analyses were performed primarily on the Intent to Treat (ITT) population defined as all subjects who have received at least one dose of study drug with a baseline (Day 1) evaluation meeting the study entry criteria.

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.

Outcome measures

Measure	Placebo n=157 Participants Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks.	0.50% Prasterone (DHEA) n=325 Participants Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks.
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity Baseline	2.43 units on a scale Standard Error 0.06	2.45 units on a scale Standard Error 0.05
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity Change from Baseline to Week 12	-0.37 units on a scale Standard Error 0.07	-0.69 units on a scale Standard Error 0.05
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity Week 12	2.06 units on a scale Standard Error 0.06	1.75 units on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Efficacy analyses were performed primarily on the Intent to Treat (ITT) population defined as all subjects who have received at least one dose of study drug with a baseline (Day 1) evaluation meeting the study entry criteria.

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.

Outcome measures

Measure	Placebo n=157 Participants Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks.	0.50% Prasterone (DHEA) n=325 Participants Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks.
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness Baseline	2.76 units on a scale Standard Error 0.05	2.83 units on a scale Standard Error 0.03
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness Change from Baseline to Week 12	-0.36 units on a scale Standard Error 0.06	-0.74 units on a scale Standard Error 0.05
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness Week 12	2.41 units on a scale Standard Error 0.05	2.09 units on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Efficacy analyses were performed primarily on the Intent to Treat (ITT) population defined as all subjects who have received at least one dose of study drug with a baseline (Day 1) evaluation meeting the study entry criteria.

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.

Outcome measures

Measure	Placebo n=157 Participants Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks.	0.50% Prasterone (DHEA) n=325 Participants Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks.
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color Week 12	2.34 units on a scale Standard Error 0.05	2.03 units on a scale Standard Error 0.04
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color Change from Baseline to Week 12	-0.33 units on a scale Standard Error 0.06	-0.73 units on a scale Standard Error 0.05
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color Baseline	2.67 units on a scale Standard Error 0.05	2.75 units on a scale Standard Error 0.03

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

0.50% Prasterone (DHEA)

Serious events: 5 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=180 participants at risk Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks.	0.50% Prasterone (DHEA) n=374 participants at risk Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks
Gastrointestinal disorders Colitis ulcerative	0.00% 0/180 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)	0.27% 1/374 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)
Injury, poisoning and procedural complications Post-procedural complication	0.00% 0/180 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)	0.27% 1/374 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/180 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)	0.27% 1/374 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)
Surgical and medical procedures Gastric bypass	0.00% 0/180 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)	0.27% 1/374 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)
Surgical and medical procedures Hernia hiatus repair	0.00% 0/180 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)	0.27% 1/374 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)
Surgical and medical procedures Knee arthroplasty	0.00% 0/180 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)	0.27% 1/374 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)

Other adverse events

Measure	Placebo n=180 participants at risk Placebo: Placebo vaginal ovule; daily dosing with one ovule for 12 weeks.	0.50% Prasterone (DHEA) n=374 participants at risk Prasterone (DHEA): Vaginal ovule containing 0.50% (6.5 mg) prasterone; daily dosing with one ovule for 12 weeks
General disorders Application site discharge	5.6% 10/180 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)	6.4% 24/374 • From Baseline to Week 12 (+ 30-day follow-up period after last dose)

Additional Information

Director of Data Analysis

Endoceutics

Phone: 418-653-0033

Email: celine.martel@endoceutics.com

Results disclosure agreements

• Principal investigator is a sponsor employee Investigators shall provide to the SPONSOR 30 days prior to submission all documents for publication, presentation, etc that report any trial results. The SPONSOR shall have editorial rights on documents and the right to review/comment with regard to (1) proprietary information, (2) accuracy of the information, (3) correctness of the scientific evaluation/conclusions and (4) to ensure that the information is fairly balanced and in compliance with regulations.
• Publication restrictions are in place

Restriction type: OTHER