This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Dose-Finding Safety and Efficacy Trial of Org 50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (177001/P06472/MK-8265-013) (NCT00535288), a randomized phase 3 study. The primary outcome is Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00535288 |
| Phase | Phase 3 |
| Condition | Postmenopausal Symptoms, Menopause, Vasomotor Symptoms |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 946 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Postmenopausal participants with moderate to severe vasomotor symptoms associated with menopause. The primary endpoint analysis population is described as the Intent-to-Treat population: randomized participants with at least one pre-baseline and at least one post-baseline weekly average of hot-flush frequency.
Intervention
Oral esmirtazapine once daily at 2.25 mg, 4.5 mg, 9 mg, or 18 mg, for up to 12 weeks.
Comparator
Encapsulated placebo tablets taken orally once daily for up to 12 weeks.
Primary question
How did average daily frequency and severity of hot flushes change from baseline during treatment, including at 4 and 12 weeks? The specified primary endpoint is change in average daily frequency of moderate or severe vasomotor symptoms at Week 4.
The study focused on moderate to severe hot flushes associated with menopause. Participants recorded symptoms daily, and the primary frequency measure counted moderate and severe hot flushes. The trial description identifies frequency and severity at 4 and 12 weeks as co-primary efficacy endpoints. The registry record also gives a specific primary outcome definition for frequency at Week 4. Numerical changes in frequency or severity, and comparisons between each dose and placebo, are not reported in the registry record. Consequently, the clinical question can be described from the registered design and endpoints, but the posted information does not establish the size or direction of any treatment-group differences.
3. Trial Design
This was a phase 3, randomized, parallel-group, placebo-controlled trial. The registry classifies masking as quadruple; the official title describes the study as double-blind. The registry lists 946 participants enrolled. That enrollment figure is the overall trial figure and does not, by itself, establish how many participants contributed to a particular endpoint analysis.
Five groups are described: placebo and esmirtazapine at 2.25 mg, 4.5 mg, 9 mg, or 18 mg. Each assigned study treatment was an encapsulated tablet taken orally once daily for up to 12 weeks. The study was designed to investigate efficacy and safety across the four active doses compared with placebo. It is therefore a dose-finding comparison, rather than a single-dose comparison.
The primary efficacy description focuses on change from baseline in average daily frequency of moderate or severe vasomotor symptoms at Week 4. The trial summary also identifies frequency and severity at 4 and 12 weeks as co-primary endpoints. Secondary outcomes include weekly changes in frequency, severity, and composite symptom scores, as well as responder and remitter counts. The registry lists 14 outcome measures and 16 analyses.
The study is marked completed. Its listed start date is 2004-09-15, and its primary completion date is 2006-01-15. The registry record does not report the allocation ratio, the number assigned to each group at randomization, or the detailed statistical analysis plan. Numerical efficacy estimates and their uncertainty are also not reported in the registry record, so the design alone cannot establish what the comparisons found.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 946 participants were randomly assigned in this study, however, one participant assigned to placebo never received treatment and one participant assigned to placebo actually received esmirtazapine 18 mg and is included in that group for all study analyses.
Overall Study
| Stage | Placebo | Esmirtazapine 2.25 mg | Esmirtazapine 4.5 mg | Esmirtazapine 9 mg | Esmirtazapine 18 mg |
|---|---|---|---|---|---|
| STARTED | 314 | 162 | 160 | 151 | 158 |
| COMPLETED | 260 | 130 | 127 | 122 | 116 |
| NOT COMPLETED | 54 | 32 | 33 | 29 | 42 |
Reasons for not completing this period:
| Reason | Placebo | Esmirtazapine 2.25 mg | Esmirtazapine 4.5 mg | Esmirtazapine 9 mg | Esmirtazapine 18 mg |
|---|---|---|---|---|---|
| Adverse Event | 20 | 19 | 25 | 20 | 30 |
| Lost to Follow-up | 0 | 3 | 0 | 0 | 0 |
| Lack of Efficacy | 26 | 3 | 4 | 4 | 7 |
| Unwilling to cooperate | 6 | 6 | 3 | 3 | 4 |
| Other | 2 | 1 | 1 | 2 | 1 |
Analysis population for the primary outcome, as defined in the registry: The Intent-to-Treat (ITT) population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Placebo | Esmirtazapine 2.25 mg | Esmirtazapine 4.5 mg | Esmirtazapine 9 mg | Esmirtazapine 18 mg | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 314 | 162 | 160 | 151 | 158 | 945 | |
| Age, Continuous | Years | 53.5 (SD 4.9) | 53.8 (SD 5.0) | 53.7 (SD 4.8) | 54.7 (SD 4.6) | 53.5 (SD 4.7) | 53.8 (SD 4.8) |
| Sex: Female, Male: Female | Participants | 314 | 162 | 160 | 151 | 158 | 945 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4, measured over Baseline and Week 4.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Events per day |
| Endpoint classification | Event-Rate Endpoint |
The specified primary endpoint is change from baseline in average daily frequency of moderate and severe vasomotor symptoms at Week 4, measured in events per day. Frequency Score A is defined as the number of moderate hot flushes plus the number of severe hot flushes in a day. Participants recorded symptoms daily on an electronic diary card during screening and treatment. The baseline average could use at most 7 completely observed pre-treatment days.
Daily symptom counts make it possible to describe the frequency of episodes over time, rather than relying only on a participant’s retrospective summary at a visit. The measure is restricted to moderate and severe symptoms, so it does not count mild symptoms in this score. The trial also lists severity as a co-primary efficacy dimension in its summary, but the specified Week 4 primary outcome is frequency.
As a general statistical point, a change-from-baseline endpoint compares a follow-up measure with a participant’s starting level. That can help express how symptom frequency changed during the treatment period, while interpretation still depends on the between-group estimates, their precision, and the analysis method. The registry record describes how the measure was constructed but does not report the Week 4 group estimates, standard deviations, or treatment comparisons. The direction and magnitude of change are therefore not available from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes that this trial compared four esmirtazapine doses with placebo and specified changes in vasomotor symptom frequency and severity as efficacy outcomes. It does not report numerical results for the primary endpoint or the other efficacy outcomes. No group means, changes from baseline, between-group contrasts, confidence intervals, or efficacy p-values are reported in the registry record. The available information therefore supports a description of the question and measurement approach, but not a conclusion about the observed efficacy difference or its precision.
The primary outcome is a change in average daily frequency of moderate and severe hot flushes at Week 4. For an efficacy interpretation, the important comparison would be the difference in change between each dose group and placebo, together with uncertainty around each estimate. A change within one group alone would not establish that the group changed more or less than placebo. No such comparisons are present in the registry record.
The trial summary calls frequency and severity at 4 and 12 weeks co-primary efficacy endpoints, while the detailed primary outcome description identifies frequency at Week 4. This means the registered description spans more than one outcome dimension and assessment time. The record does not report how results across these endpoints were combined or how interpretation accounted for multiple comparisons. Without that information and the numerical estimates, it is not possible to determine whether the findings were consistent across time points, symptom dimensions, or doses.
The registry reports safety counts by treatment group. These counts describe participants recorded as affected by serious adverse events and by other adverse events, but they do not provide enough detail to assess the full clinical context, timing, duration, or relationship of each event to treatment. The number of deaths is not reported in the registry record. Adverse event counts should not be treated as efficacy evidence.
In general, confidence intervals communicate the range of effect estimates compatible with the data under the analysis assumptions. Without posted effect estimates and intervals, statistical precision cannot be evaluated. The record also does not provide a detailed analysis plan, so the exact model, handling of all missing observations, and adjustment strategy for the multiple dose and endpoint comparisons are not reported in the registry record.
9. Statistical Methods Explained
The primary endpoint is a repeated symptom measure: participants recorded hot-flush frequency each day, and the analysis used average daily counts over baseline and treatment weeks. Frequency Score A includes moderate and severe episodes. The unit, events per day, expresses a count relative to a day of observation. In general, a rate or average count is useful when the amount of observation can vary, but interpretation depends on how the observation period and incomplete diary data are handled. The registry describes diary completion rules but does not report a statistical model for the treatment comparisons.
The endpoint description says baseline was derived from at most 7 completely observed pre-treatment days. During treatment, a weekly average was calculated when at least 4 days with non-missing data were completely observed. If fewer than 4 days were complete, the average from the previous week was carried forward. If Week 1 did not have sufficient observed days, the baseline value was carried forward. This is a last observation carried forward approach, abbreviated LOCF in the registry description.
As a general explanation, LOCF fills a missing later value with an earlier observed value. This keeps a value available for analysis but assumes, for the imputed interval, that the carried-forward value is an appropriate substitute for what would otherwise have been observed. If symptoms change after the last observation, that assumption may not represent the unobserved course. Carrying baseline forward when Week 1 data are insufficient similarly assigns the starting value to that missing weekly measure. The registry record does not report sensitivity analyses that test alternative assumptions about missing diary data.
The defined primary analysis population is the Intent-to-Treat population, consisting of all randomized participants with at least one pre-baseline and at least one post-baseline weekly average of hot-flush frequency. This definition includes randomized participants who meet the stated availability requirement; it is not simply all enrolled participants. The overall enrollment is 946, but the registry record does not report the number included in the primary endpoint analysis or the number with data in each treatment group.
The study has five parallel groups: placebo and four esmirtazapine doses. In general, a parallel-group design compares outcomes across groups assigned to different treatments over the same trial period. Randomization is intended to support a fair comparison by allocating participants without a predictable treatment-selection rule, although the allocation ratio and randomization procedure are not reported in the registry record. The listed quadruple masking indicates the registry’s classification of masking; the official title uses the description double-blind. Further details about who was masked and how masking was maintained are not reported in the registry record.
The endpoint metadata identifies mean and standard deviation as the measure and dispersion. In general, a mean describes the average outcome, while a standard deviation describes variation among observations around that mean. These summaries can help characterize the data, but a mean and standard deviation alone do not specify the treatment effect, its uncertainty, or the comparison method. No observed means, standard deviations, effect estimates, confidence intervals, or p-values are reported for the primary endpoint.
The trial is described as investigating four doses against placebo, and the outcome list includes multiple symptom measures and assessment times. General statistical practice distinguishes a prespecified primary comparison from additional exploratory comparisons, because testing many doses, outcomes, and time points creates more opportunities for apparently notable findings. The detailed hierarchy of comparisons, model specification, covariate adjustment, and any multiplicity procedure are not reported in the registry record. They should not be inferred from the existence of several outcomes.
The record lists 14 outcome measures and 16 analyses. This indicates that the registered results involve multiple outcome and analysis entries, but it does not reveal their statistical specifications. The registry record does not report whether the analysis used a repeated-measures model, a count model, or another method. Although the outcome is based on event frequency, the exact inferential model cannot be identified from the endpoint description alone. General methods for count data may account for over-dispersion, which occurs when observed variation exceeds what a simple count model assumes, but the use of such a method in this trial is not reported in the registry record.
Sample-size figures, when presented as planning illustrations, are not observed power. A planning illustration asks how many participants per arm might be needed under specified assumptions; it does not show the probability that the completed study detected an effect. The registry record does not report the trial’s own sample-size justification, target effect, or detailed power calculation. Any protocol-specific justification or interim-analysis plan is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity is relevant because the trial description includes four active doses, placebo, more than one symptom dimension, and more than one assessment time. The summary identifies frequency and severity at 4 and 12 weeks as co-primary efficacy endpoints; the detailed primary outcome entry specifies frequency at Week 4. The secondary outcomes add weekly frequency, severity, composite scores, and responder and remitter counts. When many comparisons are considered, general statistical practice may control the overall chance of false-positive findings through a prespecified testing strategy. The registry record does not report a multiplicity-adjustment method or a hierarchy for interpreting these outcomes.
The primary outcome definition includes specific rules for incomplete diary weeks. At least 4 fully observed days were required for a weekly average; when fewer days were available, the previous week’s average was carried forward, with baseline carried forward if Week 1 data were insufficient. These are the reported missing-data rules for this endpoint. Additional sensitivity analyses, reasons for missing diary entries, and the extent of missingness by group are not reported in the registry record.
The defined Intent-to-Treat population requires randomization and at least one pre-baseline and one post-baseline weekly average. The record does not report how many participants met that definition, how many were excluded from the analysis, or whether other analysis populations were used for efficacy or safety. The number randomized to each group is also not reported in the registry record. The enrollment figure alone does not supply those analysis counts.
Methods for handling missing values in outcomes other than the specified primary endpoint, as well as protocol deviations and withdrawals, are not reported in the registry record. The sponsor’s detailed statistical analysis plan, including any planned interim analyses, is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Placebo | 2 | 314 | 0.6% |
| Esmirtazapine 2.25 mg | 1 | 162 | 0.6% |
| Esmertazapine 4.5 mg | 1 | 160 | 0.6% |
| Esmirtazapine 9 mg | 3 | 151 | 2.0% |
| Esmirtazapine 18 mg | 1 | 158 | 0.6% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 91 of 314 |
| Esmirtazapine 2.25 mg | 71 of 162 |
| Esmertazapine 4.5 mg | 70 of 160 |
| Esmirtazapine 9 mg | 58 of 151 |
| Esmirtazapine 18 mg | 80 of 158 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | Esmirtazapine 2.25 mg | Esmertazapine 4.5 mg | Esmirtazapine 9 mg | Esmirtazapine 18 mg |
|---|---|---|---|---|---|---|
| Syncope vasovagal | Nervous system disorders | 1 of 314 | 0 of 162 | 0 of 160 | 0 of 151 | 1 of 158 |
| Wolff-Parkinson-White Syndrome | Cardiac disorders | 0 of 314 | 0 of 162 | 0 of 160 | 1 of 151 | 0 of 158 |
| Diverticular perforation | Gastrointestinal disorders | 0 of 314 | 1 of 162 | 0 of 160 | 0 of 151 | 0 of 158 |
| Asthenia | General disorders | 0 of 314 | 0 of 162 | 0 of 160 | 1 of 151 | 0 of 158 |
| Non-cardiac chest pain | General disorders | 0 of 314 | 0 of 162 | 0 of 160 | 1 of 151 | 0 of 158 |
| Diverticulitis | Infections and infestations | 0 of 314 | 0 of 162 | 1 of 160 | 0 of 151 | 0 of 158 |
| Ovarian fibroma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 314 | 0 of 162 | 0 of 160 | 1 of 151 | 0 of 158 |
| Nightmare | Psychiatric disorders | 1 of 314 | 0 of 162 | 0 of 160 | 0 of 151 | 0 of 158 |
| Suicidal ideation | Psychiatric disorders | 1 of 314 | 0 of 162 | 0 of 160 | 0 of 151 | 0 of 158 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Esmirtazapine 2.25 mg | Esmertazapine 4.5 mg | Esmirtazapine 9 mg | Esmirtazapine 18 mg |
|---|---|---|---|---|---|---|
| Fatigue | General disorders | 9 of 314 | 16 of 162 | 26 of 160 | 16 of 151 | 23 of 158 |
| Somnolence | Nervous system disorders | 6 of 314 | 19 of 162 | 21 of 160 | 11 of 151 | 27 of 158 |
| Headache | Nervous system disorders | 33 of 314 | 14 of 162 | 9 of 160 | 5 of 151 | 13 of 158 |
| Weight increased | Investigations | 6 of 314 | 7 of 162 | 13 of 160 | 11 of 151 | 18 of 158 |
| Increased appetite | Metabolism and nutrition disorders | 4 of 314 | 8 of 162 | 8 of 160 | 10 of 151 | 14 of 158 |
| Dry mouth | Gastrointestinal disorders | 6 of 314 | 8 of 162 | 7 of 160 | 12 of 151 | 9 of 158 |
| Dizziness | Nervous system disorders | 12 of 314 | 8 of 162 | 4 of 160 | 5 of 151 | 13 of 158 |
| Influenza | Infections and infestations | 15 of 314 | 9 of 162 | 3 of 160 | 6 of 151 | 2 of 158 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 16 of 314 | 6 of 162 | 4 of 160 | 3 of 151 | 6 of 158 |
| Menopausal symptoms | Reproductive system and breast disorders | 8 of 314 | 5 of 162 | 10 of 160 | 6 of 151 | 4 of 158 |
Serious events with the highest arm-level rate: wolff-parkinson-white syndrome (0.7%), asthenia (0.7%), non-cardiac chest pain (0.7%), ovarian fibroma (0.7%), syncope vasovagal (0.6%).
The registry lists serious adverse event and other adverse event counts for each treatment group. In the placebo group, 2 of 314 participants at risk were affected by serious adverse events, and 91 of 314 were affected by other adverse events. For esmirtazapine 2.25 mg, the corresponding counts were 1 of 162 and 71 of 162. For 4.5 mg, they were 1 of 160 and 70 of 160; for 9 mg, 3 of 151 and 58 of 151; and for 18 mg, 1 of 158 and 80 of 158.
These are counts of participants affected, not counts of every event experienced. Serious and other adverse events are separate registry categories; the record does not explain whether an individual participant could appear in both categories. The listed serious-event terms include Wolff-Parkinson-White Syndrome, Asthenia, Non-cardiac chest pain, Ovarian fibroma, Syncope vasovagal, and Diverticulitis, with the percentages recorded alongside those terms. The registry record does not give the context needed to attribute each listed term to a specific treatment group.
The death values are not reported in the registry record. These adverse-event summaries do not provide event timing, duration, severity beyond the serious classification, or investigator assessments of relatedness. The counts are descriptive and do not, on their own, establish a causal treatment effect or a comparative safety conclusion.
12. What the Result Does, and Does Not, Mean
The trial design addresses a dose-finding question: it compares four daily esmirtazapine doses with placebo for moderate to severe menopausal vasomotor symptoms. Its primary endpoint is change in average daily frequency of moderate and severe hot flushes at Week 4, with the trial summary also identifying frequency and severity at 4 and 12 weeks as co-primary efficacy endpoints. This describes what the study set out to assess.
The posted registry information does not report the numerical efficacy results. It therefore does not show whether hot-flush frequency or severity changed in any group, how the dose groups compared with placebo, or how large and precise any difference was. A study objective and outcome definition are not a substitute for results. No conclusion about an efficacy effect can be drawn from the design description alone.
Likewise, adverse-event counts are descriptive information, not a complete comparison of harms. The registry provides affected-participant counts by group, but does not provide event-level details, timing, relatedness, or death counts. Those limits matter when interpreting differences in the listed counts.
In general, a treatment comparison is more informative when its estimate is presented with uncertainty and interpreted alongside the design, missing-data assumptions, and the complete set of planned comparisons. The record’s diary rules and analysis-population definition help explain how the primary outcome was intended to be assembled, but the detailed model and statistical plan are not reported in the registry record. Thus, the posted information supports a description of the trial’s question and methods, but not an evidence-based statement about the magnitude, precision, or clinical importance of its efficacy findings.
13. Why This Trial Matters Statistically
This trial is statistically notable for its combination of a dose-finding design and repeated symptom measurement. The five groups allow a planned comparison across placebo and four esmirtazapine doses, while daily diary entries are condensed into average daily frequency measures over baseline and treatment weeks. The endpoint therefore depends on both the underlying symptom reports and rules for converting diary observations into weekly values.
The registered endpoint definition makes the missing-data approach especially relevant. Weekly averages require a minimum amount of observed diary information, and weeks below that threshold use a carried-forward value. As a general statistical principle, such rules influence which values enter the analysis and how unobserved periods are represented. Knowing the rule is useful, but evaluating its consequences also requires information about missingness and sensitivity analyses, which are not reported in the registry record.
There are also several dimensions to interpretation: four doses, frequency and severity outcomes, and multiple assessment times. The record identifies co-primary outcomes and a larger set of secondary outcomes, but does not report how multiplicity was handled. That makes it important to distinguish the registered study question from any single isolated comparison and to consider whether results are consistent across doses and endpoints. Numerical efficacy results are not reported in the registry record, so those comparisons cannot be evaluated from the posted information.
Finally, the record illustrates why design, endpoint construction, and results must be read separately. Randomization and masking describe features intended to support a fair comparison; diary definitions specify how an outcome is measured; neither provides the missing estimates or their precision. The absence of reported efficacy estimates limits statistical interpretation, even though the design and endpoint rules are described in detail.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation of the posted record for interpreting efficacy is that it does not report numerical primary or secondary outcome results. There are no group-level changes, between-group estimates, confidence intervals, or p-values in the registry record. The direction, magnitude, and precision of any treatment differences therefore cannot be assessed.
The registry’s summary describes frequency and severity at 4 and 12 weeks as co-primary endpoints, while the detailed primary outcome entry specifies frequency at Week 4. The record does not explain the hierarchy among those measures or how multiple comparisons were handled. It also does not report the statistical model, adjustment for baseline values, or sensitivity analyses for missing data.
The primary endpoint uses diary data and LOCF rules when a week has insufficient observed days. The amount and pattern of missing diary information, the number of participants meeting the Intent-to-Treat analysis definition, and the number analyzed in each group are not reported in the registry record. The overall enrollment of 946 does not resolve those gaps.
For safety, the record gives affected-participant counts but not full event narratives, timing, duration, relatedness, or death counts. It does not report the sample-size justification or interim-analysis plan. These limitations concern the information available in the registry record; they do not establish what may have been reported elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Dose-Finding Safety and Efficacy Trial of Org 50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (177001/P06472/MK-8265-013) — NCT00535288.
- Registry record last updated 2019-04-02; status last verified 2019-03.
- Results first posted 2014-07-30.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00535288 is a completed phase 3 randomized, parallel-group, placebo-controlled trial of esmirtazapine for moderate to severe menopausal vasomotor symptoms. The listed enrollment is 946. The five treatment groups were placebo and esmirtazapine at 2.25 mg, 4.5 mg, 9 mg, or 18 mg, taken orally once daily for up to 12 weeks. The registry classifies masking as quadruple.
The primary outcome description concerns change from baseline in average daily frequency of moderate and severe hot flushes at Week 4, based on daily electronic diary entries. The trial summary also identifies frequency and severity at 4 and 12 weeks as co-primary efficacy endpoints. The primary endpoint analysis population is defined as randomized participants with at least one pre-baseline and one post-baseline weekly average.
Serious and other adverse-event counts are listed by treatment group. Numerical efficacy outcomes, detailed analysis methods, multiplicity procedures, and death counts are not reported in the registry record.