Trial Outcomes & Findings for DHEA Against Vaginal Atrophy - 3-Month Efficacy Study (NCT NCT01256684)

NCT ID: NCT01256684

Last Updated: 2017-06-26

Results Overview

The percentage of parabasal cell 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 the 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: 255 participants
• Primary outcome timeframe: Baseline and Week 12
• Results posted on: 2017-06-26

Participant Flow

A total of 464 subjects were screened at 33 medical/research sites located in the US (24 centers) and Canada (9 centers) and 255 subjects were randomized. The first subject first visit was on 30-NOV-2010 and the last subject last visit was on 29-JUL-2011.

Participant milestones

Measure	Placebo Placebo: Placebo vaginal suppository	0.25% DHEA DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
Overall Study STARTED	81	87	87
Overall Study Safety Population	80	86	87
Overall Study ITT Population	77	79	81
Overall Study COMPLETED	72	74	76
Overall Study NOT COMPLETED	9	13	11

Reasons for withdrawal

Measure	Placebo Placebo: Placebo vaginal suppository	0.25% DHEA DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
Overall Study Adverse Event	1	4	2
Overall Study Withdrawal by Subject	4	0	2
Overall Study Physician Decision	0	1	0
Overall Study Lack of Efficacy	0	1	1
Overall Study Entry criteria not met/non-compliance	4	7	6

Baseline Characteristics

DHEA Against Vaginal Atrophy - 3-Month Efficacy Study

Baseline characteristics by cohort

Measure	Placebo n=80 Participants Placebo: Placebo vaginal suppository	0.25% DHEA n=86 Participants DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA n=87 Participants DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.	Total n=253 Participants Total of all reporting groups
Age, Continuous	58.81 years STANDARD_DEVIATION 5.89 • n=5 Participants	59.37 years STANDARD_DEVIATION 6.39 • n=7 Participants	57.51 years STANDARD_DEVIATION 5.63 • n=5 Participants	58.55 years STANDARD_DEVIATION 6.01 • n=4 Participants
Sex/Gender, Customized Female	80 Participants n=5 Participants	86 Participants n=7 Participants	87 Participants n=5 Participants	253 Participants n=4 Participants
Race/Ethnicity, Customized White Caucasian	69 Participants n=5 Participants	81 Participants n=7 Participants	83 Participants n=5 Participants	233 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	9 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	16 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 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 parabasal cell 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 the 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=77 Participants Placebo: Placebo vaginal suppository	0.25% DHEA n=79 Participants DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA n=81 Participants DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear Baseline	68.48 Percentage of parabasal cells Standard Error 4.41	65.72 Percentage of parabasal cells Standard Error 4.56	65.05 Percentage of parabasal cells Standard Error 4.63
Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear Week 12	66.86 Percentage of parabasal cells Standard Error 4.37	28.43 Percentage of parabasal cells Standard Error 3.62	17.65 Percentage of parabasal cells Standard Error 2.87
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	-1.62 Percentage of parabasal cells Standard Error 3.22	-37.29 Percentage of parabasal cells Standard Error 4.16	-47.40 Percentage of parabasal cells Standard Error 4.72

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 cell 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 the 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=77 Participants Placebo: Placebo vaginal suppository	0.25% DHEA n=79 Participants DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA n=81 Participants DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
Change From Baseline to Week 12 in Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear Baseline	0.73 Percentage of superficial cells Standard Error 0.15	0.68 Percentage of superficial cells Standard Error 0.13	0.68 Percentage of superficial cells Standard Error 0.12
Change From Baseline to Week 12 in Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear Week 12	1.64 Percentage of superficial cells Standard Error 0.33	5.43 Percentage of superficial cells Standard Error 0.57	6.30 Percentage of superficial cells Standard Error 0.59
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	0.91 Percentage of superficial cells Standard Error 0.31	4.75 Percentage of superficial cells Standard Error 0.58	5.62 Percentage of superficial cells Standard Error 0.61

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=77 Participants Placebo: Placebo vaginal suppository	0.25% DHEA n=79 Participants DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA n=81 Participants DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
Change From Baseline to Week 12 in Vaginal pH Baseline	6.51 units on a scale Standard Error 0.07	6.48 units on a scale Standard Error 0.07	6.47 units on a scale Standard Error 0.07
Change From Baseline to Week 12 in Vaginal pH Week 12	6.31 units on a scale Standard Error 0.09	5.70 units on a scale Standard Error 0.11	5.43 units on a scale Standard Error 0.10
Change From Baseline to Week 12 in Vaginal pH Change from Baseline to Week 12	-0.21 units on a scale Standard Error 0.08	-0.77 units on a scale Standard Error 0.10	-1.04 units on a scale Standard Error 0.11

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=77 Participants Placebo: Placebo vaginal suppository	0.25% DHEA n=79 Participants DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA n=81 Participants DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
Change From Baseline to Week 12 in Severity of the Most Bothersome Symptom of Dyspareunia Baseline	2.58 units on a scale Standard Error 0.06	2.56 units on a scale Standard Error 0.06	2.63 units on a scale Standard Error 0.05
Change From Baseline to Week 12 in Severity of the Most Bothersome Symptom of Dyspareunia Week 12	1.71 units on a scale Standard Error 0.11	1.54 units on a scale Standard Error 0.12	1.36 units on a scale Standard Error 0.12
Change From Baseline to Week 12 in Severity of the Most Bothersome Symptom of Dyspareunia Change from Baseline to Week 12	-0.87 units on a scale Standard Error 0.11	-1.01 units on a scale Standard Error 0.11	-1.27 units on a scale Standard Error 0.11

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 have 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=60 Participants Placebo: Placebo vaginal suppository	0.25% DHEA n=70 Participants DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA n=62 Participants DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
Change From Baseline to Week 12 in Severity of Vaginal Dryness Baseline	2.33 units on a scale Standard Error 0.06	2.20 units on a scale Standard Error 0.05	2.37 units on a scale Standard Error 0.06
Change From Baseline to Week 12 in Severity of Vaginal Dryness Week 12	1.32 units on a scale Standard Error 0.12	0.91 units on a scale Standard Error 0.10	0.92 units on a scale Standard Error 0.10
Change From Baseline to Week 12 in Severity of Vaginal Dryness Change from Baseline to Week 12	-1.02 units on a scale Standard Error 0.14	-1.29 units on a scale Standard Error 0.11	-1.45 units on a scale Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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 DHEA suppositories, 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 then 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=77 Participants Placebo: Placebo vaginal suppository	0.25% DHEA n=79 Participants DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA n=81 Participants DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions Baseline	2.78 units on a scale Standard Error 0.08	2.81 units on a scale Standard Error 0.07	2.83 units on a scale Standard Error 0.08
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions Week 12	2.36 units on a scale Standard Error 0.08	2.10 units on a scale Standard Error 0.09	1.95 units on a scale Standard Error 0.08
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions Change from Baseline to Week 12	-0.42 units on a scale Standard Error 0.08	-0.71 units on a scale Standard Error 0.09	-0.88 units on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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 DHEA suppositories, 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 then 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=77 Participants Placebo: Placebo vaginal suppository	0.25% DHEA n=79 Participants DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA n=81 Participants DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity Baseline	2.58 units on a scale Standard Error 0.09	2.57 units on a scale Standard Error 0.10	2.57 units on a scale Standard Error 0.10
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity Week 12	2.13 units on a scale Standard Error 0.09	1.92 units on a scale Standard Error 0.09	1.69 units on a scale Standard Error 0.09
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity Change from Baseline to Week 12	-0.45 units on a scale Standard Error 0.08	-0.65 units on a scale Standard Error 0.09	-0.88 units on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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 DHEA suppositories, 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 then 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=77 Participants Placebo: Placebo vaginal suppository	0.25% DHEA n=79 Participants DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA n=81 Participants DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness Baseline	2.91 units on a scale Standard Error 0.07	2.90 units on a scale Standard Error 0.08	2.89 units on a scale Standard Error 0.07
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness Week 12	2.57 units on a scale Standard Error 0.08	2.32 units on a scale Standard Error 0.09	2.14 units on a scale Standard Error 0.08
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness Change from Baseline to Week 12	-0.34 units on a scale Standard Error 0.07	-0.58 units on a scale Standard Error 0.09	-0.75 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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 DHEA suppositories, 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 then analyzed using the 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=77 Participants Placebo: Placebo vaginal suppository	0.25% DHEA n=79 Participants DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA n=81 Participants DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color Baseline	2.82 units on a scale Standard Error 0.08	2.94 units on a scale Standard Error 0.08	2.94 units on a scale Standard Error 0.08
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color Week 12	2.56 units on a scale Standard Error 0.08	2.27 units on a scale Standard Error 0.10	2.05 units on a scale Standard Error 0.09
Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color Change from Baseline to Week 12	-0.26 units on a scale Standard Error 0.07	-0.67 units on a scale Standard Error 0.09	-0.89 units on a scale Standard Error 0.10

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

0.25% DHEA

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

0.50% DHEA

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=80 participants at risk Placebo: Placebo vaginal suppository	0.25% DHEA n=86 participants at risk DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA n=87 participants at risk DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/80 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	1.2% 1/86 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	0.00% 0/87 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)
Hepatobiliary disorders Cholecystitis acute	0.00% 0/80 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	1.2% 1/86 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	0.00% 0/87 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)
Infections and infestations Bone abscess	0.00% 0/80 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	1.2% 1/86 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	0.00% 0/87 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/80 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	1.2% 1/86 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	0.00% 0/87 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)
Musculoskeletal and connective tissue disorders Kyphosis	0.00% 0/80 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	1.2% 1/86 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	0.00% 0/87 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)
Psychiatric disorders Suicidal ideation	0.00% 0/80 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	0.00% 0/86 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	1.1% 1/87 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)

Other adverse events

Measure	Placebo n=80 participants at risk Placebo: Placebo vaginal suppository	0.25% DHEA n=86 participants at risk DHEA: Vaginal suppository containing 0.25% (3.25 mg) DHEA; daily dosing with one suppository for 12 weeks.	0.50% DHEA n=87 participants at risk DHEA: Vaginal suppository containing 0.50% (6.5 mg) DHEA; daily dosing with one suppository for 12 weeks.
General disorders Application site discharge	6.2% 5/80 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	7.0% 6/86 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	5.7% 5/87 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)
Infections and infestations Urinary tract infection	5.0% 4/80 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	7.0% 6/86 • From Baseline up to 12 Weeks (+ 30-day follow-up period after last dose)	5.7% 5/87 • From Baseline up to 12 Weeks (+ 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