A Phase 3 interventional study of DHEA in Vaginal Atrophy, sponsored by EndoCeutics Inc.. Completed at 41 sites in 2 countries. Open to female participants aged 40 Years to 75 Years. Per ClinicalTrials.gov, last updated 2017-10-18.
Sponsored by EndoCeutics Inc. · Phase 3, Interventional, and Treatment
The purpose of this Phase III trial is to assess the long-term safety of intravaginal dehydroepiandrosterone (DHEA) in non-hysterectomized postmenopausal women with vaginal atrophy aged 40 to 75 years.
Main Inclusion Criteria:
Main Exclusion Criteria:
0.5% DHEA (intravaginal)
Drug: DHEA
Vaginal suppository containing 0.5% (6.5 mg) DHEA; daily dosing with one suppository for 52 weeks.
Also known as: Prasterone, Dehydroepiandrosterone, Vaginorm
Long-term Safety of Intravaginal Prasterone (DHEA): Endometrium
The long-term safety of intravaginal prasterone has been evaluated on different parameters including the endometrium. For this purpose, endometrial biopsies were performed at screening and at the end of the study (52 weeks) or at discontinuation visit for women who were exposed to intravaginal DHEA (prasterone) for at least 12 weeks. At screening, the endometrium had to be atrophic/inactive for women to be enrolled in the study. Only the end-of-study data are presented.
Time frame: Baseline and Week 52 (or discontinuation)
Long-term Safety of Intravaginal Prasterone (DHEA): Serum Steroid Levels
The long-term safety of intravaginal prasterone has been evaluated on different parameters including the serum levels of DHEA and its metabolites. For this purpose, blood samples were collected at Baseline and different post-Baseline timepoints for the determination of serum steroid levels by a central laboratory using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. The serum levels of dehydroepiandrosterone (DHEA), estradiol (E2) and testosterone (TESTO) obtained at Baseline and Week 52 as well as the change from Baseline to Week 52 are presented.
Time frame: Baseline and Week 52
Change From Baseline to Week 52 of Vaginal Cell Maturation (Percentage of Parabasal Cells).
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 52 as well as the change from Baseline to Week 52 are presented.
Time frame: Baseline and Week 52
Change From Baseline to Week 52 of Vaginal Cell Maturation (Percentage of Superficial Cells).
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 52 as well as the change from Baseline to Week 52 are presented.
Time frame: Baseline and Week 52
Change From Baseline to Week 52 of Vaginal pH.
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 52 as well as the change from Baseline to Week 52 are presented.
Time frame: Baseline and Week 52
Change From Baseline to Week 52 of Self-assessment of VVA Symptom Dyspareunia
The severity of dyspareunia was evaluated by a questionnaire. 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 52 as well as the change from Baseline to Week 52 are presented.
Time frame: Baseline and Week 52
Change From Baseline to Week 52 of Self-assessment of VVA Symptom Vaginal Dryness
The severity of vaginal dryness was evaluated by a questionnaire. 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 52 as well as the change from Baseline to Week 52 are presented.
Time frame: Baseline and Week 52
Change From Baseline to Week 52 of Self-assessment of VVA Symptom Irritation/Itching
The severity of irritation/itching was evaluated by a questionnaire. The severity of irritation/itching 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 52 as well as the change from Baseline to Week 52 are presented.
Time frame: Baseline and Week 52
A total of 798 subjects were screened at 41 medical/research sites located in the US (31 centers) and Canada (10 centers) and 530 subjects were randomized. The first subject first visit was on 30-NOV-2010 and the last subject last visit was on 16-JUL-2012.
| Milestone | 0.50% DHEA |
|---|---|
| Started | 530 |
| Safety population | 521 |
| Completed | 435 |
| Not completed | 95 |
| Withdrew: Adverse event | 29 |
| Withdrew: Lost to follow-up | 16 |
| Withdrew: Withdrawal by subject | 31 |
| Withdrew: Physician decision | 3 |
| Withdrew: Lack of efficacy | 4 |
| Withdrew: Non-compliance/sponsor decision/other | 12 |
The long-term safety of intravaginal prasterone has been evaluated on different parameters including the endometrium. For this purpose, endometrial biopsies were performed at screening and at the end of the study (52 weeks) or at discontinuation visit for women who were exposed to intravaginal DHEA (prasterone) for at least 12 weeks. At screening, the endometrium had to be atrophic/inactive for women to be enrolled in the study. Only the end-of-study data are presented.
| Participants | 0.50% DHEA |
|---|---|
| Endometrium: Atrophic/Inactive | 421 |
| Endometrium: No/Insufficient Tissue for Diagnosis | 36 |
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 52 as well as the change from Baseline to Week 52 are presented.
| percentage of parabasal cells | 0.50% DHEA |
|---|---|
| Baseline: Subgroup ALL | 55.49 ± 2.03 |
| Week 52: Subgroup ALL | 12.81 ± 0.97 |
| Change from Baseline: Subgroup ALL | -42.67 ± 1.84 |
| Baseline: Subgroup VVA | 63.95 ± 2.41 |
| Week 52: Subgroup VVA | 14.80 ± 1.27 |
| Change from Baseline: Subgroup VVA | -49.14 ± 2.22 |
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 52 as well as the change from Baseline to Week 52 are presented.
| percentage of superficial cells | 0.50% DHEA |
|---|---|
| Baseline: Subgroup ALL | 2.02 ± 0.19 |
| Week 52: Subgroup ALL | 9.42 ± 0.36 |
| Change from Baseline: Subgroup ALL | 7.41 ± 0.38 |
| Baseline: Subgroup VVA | 0.96 ± 0.08 |
| Week 52: Subgroup VVA | 8.81 ± 0.41 |
| Change from Baseline: Subgroup VVA | 7.85 ± 0.42 |
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 52 as well as the change from Baseline to Week 52 are presented.
| pH | 0.50% DHEA |
|---|---|
| Baseline: Subgroup ALL | 6.23 ± 0.04 |
| Week 52: Subgroup ALL | 5.09 ± 0.04 |
| Change from Baseline: Subgroup ALL | -1.14 ± 0.04 |
| Baseline: Subgroup VVA | 6.40 ± 0.04 |
| Week 52: Subgroup VVA | 5.13 ± 0.05 |
| Change from Baseline: Subgroup VVA | -1.27 ± 0.05 |
The severity of dyspareunia was evaluated by a questionnaire. 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 52 as well as the change from Baseline to Week 52 are presented.
| units on a scale | 0.50% DHEA |
|---|---|
| Baseline: Subgroup MS | 2.53 ± 0.03 |
| Week 52: Subgroup MS | 0.85 ± 0.06 |
| Change from Baseline: Subgroup MS | -1.68 ± 0.06 |
| Baseline: Subgroup MBS/MS | 2.57 ± 0.04 |
| Week 52: Subgroup MBS/MS | 0.87 ± 0.07 |
| Change from Baseline: Subgroup MBS/MS | -1.69 ± 0.07 |
The severity of vaginal dryness was evaluated by a questionnaire. 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 52 as well as the change from Baseline to Week 52 are presented.
| units on a scale | 0.50% DHEA |
|---|---|
| Baseline: Subgroup MS | 2.22 ± 0.03 |
| Week 52: Subgroup MS | 0.59 ± 0.05 |
| Change from Baseline: Subgroup MS | -1.63 ± 0.05 |
| Baseline: Subgroup MBS/MS | 2.19 ± 0.04 |
| Week 52: Subgroup MBS/MS | 0.67 ± 0.09 |
| Change from Baseline: Subgroup MBS/MS | -1.52 ± 0.09 |
The severity of irritation/itching was evaluated by a questionnaire. The severity of irritation/itching 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 52 as well as the change from Baseline to Week 52 are presented.
| units on a scale | 0.50% DHEA |
|---|---|
| Baseline: Subgroup MS | 2.10 ± 0.03 |
| Week 52: Subgroup MS | 0.60 ± 0.08 |
| Change from Baseline: Subgroup MS | -1.50 ± 0.09 |
| Baseline: Subgroup MBS/MS | 2.13 ± 0.07 |
| Week 52: Subgroup MBS/MS | 0.74 ± 0.14 |
| Change from Baseline: Subgroup MBS/MS | -1.39 ± 0.16 |
The long-term safety of intravaginal prasterone has been evaluated on different parameters including the serum levels of DHEA and its metabolites. For this purpose, blood samples were collected at Baseline and different post-Baseline timepoints for the determination of serum steroid levels by a central laboratory using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. The serum levels of dehydroepiandrosterone (DHEA), estradiol (E2) and testosterone (TESTO) obtained at Baseline and Week 52 as well as the change from Baseline to Week 52 are presented.
| pg/mL | 0.50% DHEA |
|---|---|
| DHEA: Baseline | 2071.61 ± 65.70 |
| DHEA: Week 52 | 2997.25 ± 85.23 |
| DHEA: Change from Baseline | 925.65 ± 74.35 |
| E2: Baseline | 6.05 ± 1.11 |
| E2: Week 52 | 4.46 ± 0.32 |
| E2: Change from Baseline | -1.59 ± 1.13 |
| TESTO: Baseline | 161.28 ± 6.93 |
| TESTO: Week 52 | 189.44 ± 4.79 |
| TESTO: Change from Baseline | 28.17 ± 6.55 |
Collected over From Baseline to Week 52 (+ 30-day follow-up period after last dose). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 0.50% DHEA | — | 18/521 (3.5%) | 177/521 (34%) |
| Event | 0.50% DHEA |
|---|---|
| OsteoarthritisMusculoskeletal and connective tissue disorders | 2/521 |
| Colitis ischaemicGastrointestinal disorders | 1/521 |
| Duodenal stenosisGastrointestinal disorders | 1/521 |
| DyspepsiaGastrointestinal disorders | 1/521 |
| PancreatitisGastrointestinal disorders | 1/521 |
| Infectious peritonitisInfections and infestations | 1/521 |
| Staphylococcal infectionInfections and infestations | 1/521 |
| Femur fractureInjury, poisoning and procedural complications | 1/521 |
| LacerationInjury, poisoning and procedural complications | 1/521 |
| Muscle ruptureInjury, poisoning and procedural complications | 1/521 |
| Event | 0.50% DHEA |
|---|---|
| Application site dischargeGeneral disorders | 73/521 |
| Urinary tract infectionInfections and infestations | 53/521 |
| NasopharyngitisInfections and infestations | 51/521 |
Baseline Analysis Population corresponds to the Safety Population which includes all subjects who received any amount of DHEA, and who have any safety information available.
| Age, Continuous(years) | 0.50% DHEA |
|---|---|
| Mean | 57.95 ± 5.65 |
| Sex/Gender, Customized(Participants) | 0.50% DHEA |
|---|---|
| Female | 521 |
| Race/Ethnicity, Customized(Participants) | 0.50% DHEA |
|---|---|
| White Caucasian | 478 |
| Black or African American | 31 |
| Asian | 3 |
| American Indian or Alaska Native | 3 |
| Native Hawaiian or Other Pacific Islander | 2 |
| Other | 4 |
This study is completed, as verified in Sep 2017. You cannot join it, but the record below documents what was studied.
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EndoCeutics Inc.