Trial · NCT01942668
A Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms
NCT01942668, Phase 3, Completed, TherapeuticsMD; results first posted 2019-05-06
3 sourcestrials-2026-11-12-0.5.0
Download JSON
Cite this record
ConductScience Library. A Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms. Trials, record NCT01942668. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01942668
On this page
Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms
- NCT number
- NCT01942668
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 1,845 participants, actual
- Lead sponsor
- TherapeuticsMD
- Conditions
- Menopause
- Interventions
- Estradiol, Progesterone, Placebo
- First posted
- 2013-09-16
- Last updated
- 2019-05-06
- Results first posted
- 2019-05-06
Source ClinicalTrials.gov
Registered outcomes210
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Baseline and Week 4 | Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week. |
| Primary | Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Baseline and Week 12 | Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week. |
| Primary | Co-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Baseline and Week 4 | Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). |
| Primary | Co-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Baseline and Week 12 | Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). |
| Primary | Primary Safety Endpoint: Endometrial Protection - Hyperplasia | Baseline and Month 12 | Endometrial biopsies centrally evaluated by 2 primary pathologists using criteria from Blaustein's Pathology text. Pathologists classified bx into 1 of following 3 categories: Cat.1: Non-endometrial malignancy/non-hyperplasia; Cat.2: Endometrial hyperplasia; Cat.3: Endometrial malignancy. Consensus reached when 2 primary pathologist agreed on any of above categories; if primary pathologists disagreed on presence of hyperplasia, result of 3rd pathologist was utilized and final decision regarding presence of hyperplasia was based on diagnosis of majority. If all 3 reads disparate, final diagnosis based on most severe dx. Incidence rate calculated as: I=A/B where I=incidence rate at M12 evaluation, A=all new subjects with biopsies positive for endometrial hyperplasia during study but post-Baseline, B=all subjects w/biopsies following M11 meeting criteria specified plus all subjects w/biopsies positive for endometrial hyperplasia by any pathologists before M11. |
| Secondary | Endometrial Protection - Hyperplasia | Baseline and Month 12 | Endometrial biopsies centrally evaluated by 3 primary pathologists using criteria described in Blaustein's Pathology text. Pathologists classified biopsy into 1 of following 3 categories: Cat.1: Non-endometrial malignancy/non-hyperplasia; Cat.2: Endometrial hyperplasia; Cat.3: Endometrial malignancy. Consensus was reached when the 2 of 3 pathologist readers agreed on any of the above categories; if all three reads were disparate, the final diagnosis was based on the most severe diagnosis. Incidence rate calculated as: I=A/B where I=incidence rate at M12 evaluation, A=all new subjects with biopsies positive for endometrial hyperplasia during study but post-Baseline, B=all subjects with biopsies following M11 meeting the criteria specified plus all subjects with biopsies positive for endometrial hyperplasia by any of the pathologists before M11. |
| Secondary | Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS) | Baseline and Week 1 | Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week. |
| Secondary | Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS) | Baseline and Week 2 | Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week. |
| Secondary | Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS) | Baseline and Week 3 | Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week. |
| Secondary | Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS) | Baseline and Week 4 | Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week. |
1 to 10 of 210Source ClinicalTrials.gov
See all 210 registered outcomesOutcomes210
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Baseline and Week 4 | Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP. | weekly hot flushes | MEAN |
| PRIMARY | Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Baseline and Week 12 | Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP. | weekly hot flushes | MEAN |
| PRIMARY | Co-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Baseline and Week 4 | Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP. | scores on a scale | MEAN |
| PRIMARY | Co-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Baseline and Week 12 | Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP. | scores on a scale | MEAN |
| PRIMARY | Primary Safety Endpoint: Endometrial Protection - Hyperplasia | Baseline and Month 12 | Randomized subjects who had taken at least 1 capsule, had no major protocol violations, acceptable biopsy at baseline (evaluable tissue, no endometrial hyperplasia, polyp or cancer), had a biopsy at month 12 (on or after Study Day 326) or had a diagnosis of endometrial hyperplasia prior to month 12. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Endometrial Protection - Hyperplasia | Baseline and Month 12 | Randomized subjects who had taken at least 1 capsule, had no major protocol violations, acceptable biopsy at baseline (evaluable tissue, no endometrial hyperplasia, polyp or cancer), had a biopsy at month 12 (on or after Study Day 326) or had a diagnosis of endometrial hyperplasia prior to month 12. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS) | Baseline and Week 1 | Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP. | weekly hot flushes | MEAN |
| SECONDARY | Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS) | Baseline and Week 2 | Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP. | weekly hot flushes | MEAN |
| SECONDARY | Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS) | Baseline and Week 3 | Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP. | weekly hot flushes | MEAN |
| SECONDARY | Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS) | Baseline and Week 4 | Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP. | weekly hot flushes | MEAN |
1 to 10 of 210Source ClinicalTrials.gov
See all 210 outcomesResults by group1,230
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Combined Estradiol 1 mg / Progesterone 100 mg | -40.6 | Standard Deviation 30.59 | weekly hot flushes | |
| Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Combined Estradiol 0.5 mg / Progesterone 100 mg | -35.1 | Standard Deviation 29.14 | weekly hot flushes | |
| Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Combined Estradiol 0.5 mg / Progesterone 50 mg | -33.6 | Standard Deviation 30.64 | weekly hot flushes | |
| Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Combined Estradiol 0.25 mg / Progesterone 50 mg | -38.9 | Standard Deviation 31.04 | weekly hot flushes | |
| Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Placebo | -26.4 | Standard Deviation 27.05 | weekly hot flushes | |
| Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Combined Estradiol 1 mg / Progesterone 100 mg | -55.1 | Standard Deviation 31.36 | weekly hot flushes | |
| Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Combined Estradiol 0.5 mg / Progesterone 100 mg | -53.7 | Standard Deviation 31.93 | weekly hot flushes | |
| Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Combined Estradiol 0.5 mg / Progesterone 50 mg | -50.2 | Standard Deviation 31.35 | weekly hot flushes | |
| Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Combined Estradiol 0.25 mg / Progesterone 50 mg | -52.4 | Standard Deviation 33.90 | weekly hot flushes | |
| Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) | Placebo | -40.2 | Standard Deviation 29.79 | weekly hot flushes |
1 to 10 of 1,230Source ClinicalTrials.gov
See all 1,230 results by groupParticipant flow15
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Combined Estradiol 1 mg / Progesterone 100 mg | 418 | |
| Overall Study | STARTED | Combined Estradiol 0.5 mg / Progesterone 100 mg | 426 | |
| Overall Study | STARTED | Combined Estradiol 0.5 mg / Progesterone 50 mg | 422 | |
| Overall Study | STARTED | Combined Estradiol 0.25 mg / Progesterone 50 mg | 427 | |
| Overall Study | STARTED | Placebo | 152 | |
| Overall Study | COMPLETED | Combined Estradiol 1 mg / Progesterone 100 mg | 284 | |
| Overall Study | COMPLETED | Combined Estradiol 0.5 mg / Progesterone 100 mg | 305 | |
| Overall Study | COMPLETED | Combined Estradiol 0.5 mg / Progesterone 50 mg | 312 | |
| Overall Study | COMPLETED | Combined Estradiol 0.25 mg / Progesterone 50 mg | 281 | |
| Overall Study | COMPLETED | Placebo | 93 |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 participant flowAdverse events340
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Headache | Nervous system disorders | Combined Estradiol 1 mg / Progesterone 100 mg | 31 | 415 | |
| other | Headache | Nervous system disorders | Combined Estradiol 0.5 mg / Progesterone 100 mg | 24 | 424 | |
| other | Headache | Nervous system disorders | Combined Estradiol 0.5 mg / Progesterone 50 mg | 45 | 421 | |
| other | Headache | Nervous system disorders | Combined Estradiol 0.25 mg / Progesterone 50 mg | 43 | 424 | |
| other | Headache | Nervous system disorders | Placebo | 4 | 151 | |
| other | Nasopharyngitis | Infections and infestations | Combined Estradiol 1 mg / Progesterone 100 mg | 25 | 415 | |
| other | Nasopharyngitis | Infections and infestations | Combined Estradiol 0.5 mg / Progesterone 100 mg | 41 | 424 | |
| other | Nasopharyngitis | Infections and infestations | Combined Estradiol 0.5 mg / Progesterone 50 mg | 37 | 421 | |
| other | Nasopharyngitis | Infections and infestations | Combined Estradiol 0.25 mg / Progesterone 50 mg | 24 | 424 | |
| other | Nasopharyngitis | Infections and infestations | Placebo | 4 | 151 |
1 to 10 of 340Source ClinicalTrials.gov
See all 340 adverse eventsAdverse event totals15
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Combined Estradiol 1 mg / Progesterone 100 mg | 0 | 415 |
| Total, all-cause mortality | Combined Estradiol 0.5 mg / Progesterone 100 mg | 0 | 424 |
| Total, all-cause mortality | Combined Estradiol 0.5 mg / Progesterone 50 mg | 1 | 421 |
| Total, all-cause mortality | Combined Estradiol 0.25 mg / Progesterone 50 mg | 0 | 424 |
| Total, all-cause mortality | Placebo | 0 | 151 |
| Total, other adverse events | Combined Estradiol 1 mg / Progesterone 100 mg | 324 | 415 |
| Total, other adverse events | Combined Estradiol 0.5 mg / Progesterone 100 mg | 277 | 424 |
| Total, other adverse events | Combined Estradiol 0.5 mg / Progesterone 50 mg | 291 | 421 |
| Total, other adverse events | Combined Estradiol 0.25 mg / Progesterone 50 mg | 232 | 424 |
| Total, other adverse events | Placebo | 41 | 151 |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 adverse event totalsPapers13
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT01942668
GET https://conductscience.org/api/trials/v1/NCT01942668/registered?page=2