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 Twenty-six Week Extension Trial of Org 50081 (Esmirtazapine) in Outpatients With Chronic Primary Insomnia (176003/P05721/MK-8265-007) (NCT00750919), a na phase 3 study. The primary outcome is Change From Baseline in Total Sleep Time (TST).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00750919 |
| Phase | Phase 3 |
| Condition | Sleep Initiation and Maintenance Disorders, Mental Disorders, Dyssomnias |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 184 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Outpatients with chronic primary insomnia who completed protocol 21106/P05701/MK-8265-002 (NCT00631657) were eligible to enter this extension. The registry describes the analyzed population as participants who received at least one dose of esmirtazapine in the extension. The study enrollment was 184.
Intervention
Participants received esmirtazapine as a 4.5 mg tablet taken orally once daily, for up to 6 months. The extension was open label, so treatment assignment was not masked.
Comparator
There was no control group in this single-group study. The registry does not report a randomized comparison or a like-for-like control arm. Changes from baseline therefore describe outcomes among treated participants, not a contrast against an untreated or alternative-treatment group.
Primary question
The primary outcome was change from baseline in total sleep time, measured in minutes per night, at baseline and Week 26. The endpoint uses participants’ sleep-diary reports. The registry record does not report the numerical mean change, its variability, or a statistical test for this outcome, so the size and precision of any change cannot be assessed from the posted results.
3. Trial Design
This was a Phase 3, single-group, open-label extension trial of esmirtazapine in outpatients with chronic primary insomnia. It was designed to investigate safety and explore efficacy among participants who had completed an earlier clinical trial, protocol 21106/P05701/MK-8265-002 (NCT00631657). Enrollment was 184. The registry lists the study status as terminated, with a start date of 2008-10-07 and a primary completion date of 2010-03-10.
Participants received esmirtazapine 4.5 mg orally once daily for up to 6 months. The official study title describes a twenty-six-week extension, and the primary outcome timeframe is baseline and Week 26. The study was open label, with no masking, and used a single-group model. The registry does not report a concurrent control arm or a randomized allocation. As a result, the design can describe outcomes and adverse events observed during treatment, but it cannot estimate a controlled treatment contrast.
The primary outcome was change from baseline in total sleep time (TST), in minutes per night. Secondary outcomes were change from baseline in sleep latency (SL) and wake time after sleep onset (WASO). The registry lists five outcome measures, but it reports no statistical analyses. Numerical results for the primary and secondary outcomes are not reported in the registry record. The record also does not explain why the trial was terminated or provide further details about the circumstances of termination.
The baseline for the primary outcome was the TST from the last week of the base study. This makes the extension’s baseline dependent on diary data collected in the preceding study rather than on a new, separately described screening measurement. The registry identifies the analysis population as the All-Subjects-Treated (AST) population: participants who received at least one dose of esmirtazapine in the extension.
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.
Overall Study
| Stage | Esmirtazapine |
|---|---|
| STARTED | 184 |
| COMPLETED | 126 |
| NOT COMPLETED | 58 |
Reasons for not completing this period:
| Reason | Esmirtazapine |
|---|---|
| Adverse Event | 9 |
| Withdrawal by Subject | 1 |
| Lack of Efficacy | 8 |
| Could not cooperate, unrelated to trial | 4 |
| Other | 36 |
Analysis population for the primary outcome, as defined in the registry: The All-Subjects-Treated (AST) population consisted of all participants who received at least one dose of esmertazapine in the extension study.
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 | Esmirtazapine |
|---|---|---|
| Participants analysed | 184 | |
| Age, Continuous | years | 47.8 (SD 11.5) |
| Sex: Female, Male: Female | Participants | 111 |
| Sex: Female, Male: Male | Participants | 73 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Total Sleep Time (TST), measured over Baseline and Week 26.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Minutes per night |
| Endpoint classification | Continuous Endpoint |
Total sleep time measures how long participants reported actually sleeping during the night. In this study it was based on sleep diary question 6, recorded by participants using a LogPad, a handheld electronic data-capture device. The endpoint is expressed in minutes per night and is summarized as a mean with standard deviation. Change from baseline compares the Week 26 measure with the baseline measure, defined as TST from the last week of the base study.
As a general statistical point, a continuous endpoint such as TST retains information about the size of each participant’s measured value rather than reducing the outcome to a yes-or-no category. A mean can describe the average level or average change, while a standard deviation describes how dispersed individual values are around that mean. Neither alone conveys the uncertainty around the estimated mean; that requires an uncertainty measure such as a confidence interval.
The diary-based endpoint also depends on participants recording their sleep and on enough diary entries being available to form weekly averages. The registry describes rules for using observed diary entries and for leaving some weeks missing when no diary data were available. It does not report the resulting mean change, standard deviation, or confidence interval for TST. Consequently, the endpoint’s observed direction, magnitude, and precision are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the intended primary outcome and the way diary data were processed, but it does not report a numerical result for change in TST. There is no posted mean change, standard deviation, confidence interval, or p-value for the primary outcome. The record therefore does not establish how much, in which direction, or with what precision TST changed between baseline and Week 26 in the analyzed population.
This absence matters for interpretation. A mean change would describe the average within-participant difference over the specified period, while the standard deviation would describe variation in those changes or values, depending on the reported analysis. A confidence interval would express the uncertainty around an estimate. Without these results, readers cannot assess whether the estimate is precise or compatible with a wide range of possible changes. The registry also lists changes in sleep latency and wake time after sleep onset as secondary outcomes, but their numerical results are not reported in the registry record.
Even if outcome values were available, this study’s single-group, open-label design would limit what could be attributed to the intervention. Participants entered after completing an earlier trial, there was no control group, and treatment was not masked. A before-and-after change in this setting could reflect multiple influences over time, including factors unrelated to treatment. It would not by itself separate a treatment-associated change from those other influences.
The registry lists 184 participants enrolled and defines the AST population as those who received at least one dose. It does not report the number with usable Week 26 diary data or a numerical outcome analysis population. Enrollment should therefore not be read as the count contributing complete primary-outcome data. The record lists five outcome measures and no statistical analyses. It does not report a test of the primary outcome or an inferential result that could support a claim about statistical evidence.
Overall, the posted record supports a description of the study design, the planned sleep measures, and the diary-processing approach. It does not provide the numerical efficacy results needed to quantify the observed change or its uncertainty. The design also does not include a controlled comparison, so any within-group change would require cautious interpretation rather than being treated as a causal treatment effect.
9. Statistical Methods Explained
The registry describes a continuous primary outcome: change from baseline in TST, measured in minutes per night and summarized as a mean with standard deviation. It identifies baseline as TST from the last week of the base study and gives baseline and Week 26 as the outcome timeframe. It does not report the actual mean change, standard deviation, confidence interval, or statistical test. The methods can therefore be described, but the primary estimate and its uncertainty cannot be evaluated from the posted results.
What does a mean change describe?
As a general statistical explanation, a mean change summarizes the average difference in a measurement across participants. It is a measure of the group’s average trajectory, not a statement that every participant changed by that amount. A standard deviation describes the spread of observations around a mean. It is different from a standard error, which describes the precision of an estimated mean, and from a confidence interval, which gives a range of values compatible with the data and the statistical method used. The registry identifies standard deviation as the dispersion measure but does not report a numerical value for it.
How were diary observations handled?
The registry says daily diary data were converted to weekly averages. For a treatment week with more than three non-missing morning diaries, the non-missing diary data for that week were used. When a week had three non-missing morning diaries or fewer, data from the previous week were also used, with the two weeks’ data combined as a weighted mean using the number of observed diaries as weights. If a treatment week had no diary data, it was considered missing and was not imputed.
As a general explanation, a weighted mean gives greater influence to the component with more observations. Using information from an adjacent week can retain some diary information when the current week has few entries, but it also means the weekly value may draw on observations from more than one week. Leaving a week missing rather than imputing it avoids inserting a constructed value for an entirely unobserved week. It does not, by itself, resolve possible bias if missingness is related to sleep or to other participant characteristics. The registry does not report how many weeks or participants had missing diary data, or whether any sensitivity analyses assessed the effect of missingness.
What can the single-group design estimate?
The study is listed as a single-group, open-label extension without a control arm. In general, a within-group before-and-after estimate describes the change observed among participants over time. It does not isolate the effect of treatment from changes that might have occurred without treatment, changes in reporting, or other time-related influences. Masking can reduce some forms of expectation-related influence, but this study is listed as having no masking. These design features are relevant when interpreting any observed change; they do not supply a result where none is reported.
What do the planning illustrations represent?
Any sample-size figures associated with planning are illustrations, not observed power and not the trial’s own design justification. The stated assumptions for the illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The registry does not report the trial’s own sample-size justification. Since the trial itself had one group and the numerical observed effect is not reported in the registry record, the illustrations should not be interpreted as evidence that this extension had a particular probability of detecting an effect.
As a general explanation, planning calculations use assumptions about the effect to be detected, variability, analysis method, and significance threshold to estimate a needed sample size. Changing the assumed effect changes the planning target. Such calculations are not a substitute for an observed treatment result, and they do not show whether the planned study was adequately powered unless the underlying design and assumptions are appropriate and fully reported.
What is not available for statistical review?
The registry lists five outcome measures and zero statistical analyses. It does not report the model or test used to analyze the primary endpoint, the numerical outcome estimates, their uncertainty, or an analysis-specific participant count. The record also does not report whether analyses adjusted for any covariates or how any multiplicity across outcomes was handled. Those details are not reported in the registry record, so no unreported model, test, or adjustment should be assumed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary outcome as change from baseline in TST and identifies change from baseline in sleep latency and wake time after sleep onset as secondary outcomes. It also states that five outcome measures were listed, but the record reports no statistical analyses. Numerical results and inferential tests for these outcomes are not reported in the registry record.
As a general statistical explanation, multiplicity arises when several outcomes, time points, or comparisons are tested. If many tests are conducted, the chance of at least one apparently notable result can increase. A prespecified analysis plan and any adjustment approach help readers understand how the family of tests was handled. The registry does not report a multiplicity procedure, nor does it provide enough analysis detail to determine whether one was used.
The primary endpoint used diary observations converted to weekly averages. Weeks with three non-missing morning diaries or fewer were combined with data from the previous week using a weighted mean; weeks without diary data were considered missing and were not imputed. The registry does not report the amount or pattern of missing diary data, the number contributing to the Week 26 estimate, or sensitivity analyses for missing outcomes. These omissions limit assessment of how representative the observed data might have been.
The named analysis population was AST, consisting of participants who received at least one dose. The record does not report how many of those participants contributed to each endpoint analysis. It also does not report whether participants who discontinued treatment or lacked final diary data were included in any particular analysis. Those details are 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 |
|---|---|---|---|
| Esmirtazapine | 3 | 184 | 1.6% |
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 |
|---|---|
| Esmirtazapine | 59 of 184 |
Most frequent serious adverse event terms
| Event term | Organ system | Esmirtazapine |
|---|---|---|
| Acute myocardial infarction | Cardiac disorders | 1 of 184 |
| Intervertebral disc degeneration | Musculoskeletal and connective tissue disorders | 1 of 184 |
| Strabismus correction | Surgical and medical procedures | 1 of 184 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Esmirtazapine |
|---|---|---|
| Insomnia | Psychiatric disorders | 23 of 184 |
| Nasopharyngitis | Infections and infestations | 19 of 184 |
| Weight increased | Investigations | 11 of 184 |
| Headache | Nervous system disorders | 10 of 184 |
| Somnolence | Nervous system disorders | 10 of 184 |
Serious events with the highest arm-level rate: acute myocardial infarction (0.5%), intervertebral disc degeneration (0.5%), strabismus correction (0.5%).
The registry lists 184 participants at risk for serious adverse events and 3 affected, and 184 at risk for other adverse events and 59 affected. These are participant counts, not event rates over a specified person-time period. The record does not provide additional detail about event timing, duration, severity beyond the serious/non-serious distinction, or causal attribution to esmirtazapine.
Three serious adverse event terms are listed, each with a reported frequency of 0.5%: acute myocardial infarction, intervertebral disc degeneration, and strabismus correction. The registry does not indicate in this record whether these terms account for all serious events or how events were judged related to treatment. Deaths are not reported in the registry record.
These figures are descriptive observations from an open-label, single-group extension. They do not provide a comparison against a control group, and the counts alone do not determine whether an event was caused by treatment. The registry record also does not provide further information about event-level overlap or follow-up time. Interpretation should therefore stay close to the reported counts and terms rather than extending them to comparative or causal conclusions.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a Phase 3, open-label extension study of esmirtazapine in outpatients with chronic primary insomnia who completed an earlier study. It describes a once-daily 4.5 mg oral dose for up to 6 months, a single-group design, and a primary outcome based on participants’ diary-reported total sleep time. It also specifies a rule for forming weekly diary averages and identifies the treated population used for the primary outcome.
The posted results do not establish the amount or direction of change in total sleep time. No numerical primary-outcome estimate or measure of its precision is reported in the registry record. The same is true of the listed secondary sleep outcomes. Thus, the registry record does not support a quantitative conclusion about change in sleep latency, wake time after sleep onset, or total sleep time.
More generally, a before-and-after change in an uncontrolled, unmasked extension cannot alone show that treatment caused the change. The absence of a comparator means that observed change, if reported, would not be separated from other influences over time. The extension’s enrollment also consists of people who completed an earlier study, so the findings would describe this selected group rather than automatically applying to all people with insomnia.
The safety entries describe reported counts and event terms among participants at risk. They do not provide a controlled comparison or establish causation. Overall, the registry record offers useful design and measurement details, but the absent numerical efficacy analyses and lack of a control group place clear limits on what can be concluded about treatment-associated outcomes.
13. Why This Trial Matters Statistically
This trial is statistically notable as an extension study that follows participants from an earlier protocol. Such a design can document how outcomes and safety observations are recorded during continued exposure, while the relationship to the preceding study defines the population entering the extension. Here, the registry explicitly identifies prior-study completers and defines the analysis population by receipt of at least one dose.
The study also illustrates how a patient-reported continuous outcome depends on measurement procedures. TST came from daily sleep diaries, which were converted to weekly averages, and the registry gives rules for weeks with limited diary completion. Those choices matter because the final endpoint is shaped not only by the clinical concept being measured but also by how observations are collected and summarized.
At the same time, the single-group, open-label design makes causal interpretation limited. Without a concurrent control group, a change over time cannot be cleanly separated from other influences. The absence of numerical outcome estimates in the registry record adds a further limitation: the direction, magnitude, and precision of the primary outcome cannot be examined.
For statistical readers, the record is a reminder to distinguish an outcome’s definition and data-handling rules from its results. Design details can clarify what was intended to be measured, but they cannot replace reported estimates and uncertainty. Likewise, safety counts in an uncontrolled extension are descriptive, not comparative evidence. The combination of detailed endpoint procedures and missing numerical analyses makes transparent reporting especially important for judging what the study can contribute.
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 trial-specific limitation is that the registry record does not report numerical results for the primary or secondary sleep outcomes. It gives no primary mean change, standard deviation, confidence interval, or test result. The statistical analyses are not reported, so the analysis method and the precision of any estimate cannot be reviewed.
The single-group design has no concurrent control, and treatment was open label. Consequently, any within-group change would not distinguish treatment-associated change from other changes over time or influences on self-reported diary entries. The extension population was restricted to people who completed the earlier study, and the results would not automatically represent people who did not enter or complete that earlier study.
The primary endpoint depended on diary completion and on rules that could combine observations from adjacent weeks when the current week had few entries. The registry does not report how often those rules were applied, how much data were missing, or how many participants contributed to the Week 26 analysis. It also does not report sensitivity analyses for missing diary observations.
The record lists five outcome measures but does not describe how multiplicity was handled. It does not report the study’s own sample-size justification, and the stated planning illustrations are not the trial’s design justification. The registry lists the trial status as terminated but does not report the reason. These gaps limit assessment of both the conduct and interpretation of the extension beyond the design and procedures that are explicitly described.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Twenty-six Week Extension Trial of Org 50081 (Esmirtazapine) in Outpatients With Chronic Primary Insomnia (176003/P05721/MK-8265-007) — NCT00750919.
- Registry record last updated 2021-02-02; status last verified 2021-01.
- Results first posted 2014-06-24.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
This Phase 3 trial was an open-label, single-group extension in outpatients with chronic primary insomnia who completed protocol 21106/P05701/MK-8265-002 (NCT00631657). Enrollment was 184, and the registry lists the status as terminated. Participants received esmirtazapine 4.5 mg orally once daily for up to 6 months.
The primary outcome was change from baseline in diary-reported total sleep time at Week 26, measured in minutes per night. Secondary outcomes included changes in sleep latency and wake time after sleep onset. The record describes weekly diary processing and defines the AST population as participants who received at least one dose.
Numerical efficacy results and statistical analyses are not reported in the registry record. Safety entries include 3 participants with serious adverse events and 59 with other adverse events among 184 at risk for each category.