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 Efficacy and Tolerability of Ramelteon in Patients With Rapid Eye Movement (REM) Behavior Disorder and Parkinsonism (NCT00745030), a randomized na study. The primary outcome is Change in the Frequency of RBD Based on the Daily Sleep Diaries, Completed Daily for the Duration of the Study by the Study Subjects' Bed Partners/Caregivers.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00745030 |
| Phase | NA |
| Condition | REM Behavior Disorder, Parkinsonism |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Northwestern University |
| Results posted | Yes |
2. Clinical Question
The study asked whether ramelteon could be evaluated for changes in REM behavior disorder (RBD) events among people with parkinsonism. The planned comparison was ramelteon versus placebo, with the primary outcome focused on change in RBD-event frequency recorded in daily sleep diaries by bed partners or caregivers. The registry record describes a 12-week study, but it also states that recruitment difficulties prevented enrollment of enough participants and that no data were collected.
Population
People with RBD and parkinsonism were the intended population. The brief summary describes diagnosis based on clinical interview, with confirmation by polysomnographic data. The registry record reports enrollment of 3 participants, below the planned recruitment of 20.
Intervention
Ramelteon, listed as Rozerem and as TAK-375 in the arm description, was given as 8mg tablets.
Comparator
The comparator was placebo, listed as 8 mg tablets. The study was described as randomized and placebo controlled.
Primary question
The planned primary question concerned change in RBD-event frequency, assessed using daily sleep diaries over 12 weeks. No treatment comparison for this outcome is available because the registry record states that no data were collected and data will not be analyzed.
The proposed rationale was that RBD can disrupt sleep and affect people with parkinsonism and their bed partners. The brief summary describes ramelteon as a candidate for investigation, not as an established treatment in this study. With no analyzed endpoint data, the record cannot establish whether the groups differed, how large any difference might have been, or how precisely an effect could be estimated.
3. Trial Design
The registry describes a randomized, parallel-group study with quadruple masking. The official title calls the study placebo controlled, double blind, randomized, prospective, and a pilot study. The record does not explain the difference between its quadruple-masking designation and the title’s double-blind wording, or identify which roles were masked. Those details are not reported in the registry record.
The planned arms were ramelteon (TAK-375) 8mg tablets and placebo 8 mg tablets. The brief summary describes a prospective, randomized, placebo-controlled 12-week study. It says the investigators planned to recruit 20 subjects with RBD and parkinsonism. Actual enrollment was 3. The study status is terminated, and the primary outcome description attributes termination to low enrollment and recruitment difficulties.
The record lists the study start as 2008-06 and primary completion as 2009-12. These dates describe the registry record’s study timeline; they do not establish that participants completed the planned follow-up. The primary outcome timeframe is listed as 12 weeks, but no participant-level follow-up or adherence information is reported.
The primary outcome was change in RBD frequency based on daily diaries completed by bed partners or caregivers. A secondary outcome concerned change in tonic muscle activity between baseline and final polysomnographic studies. The registry reports that no data were collected and the data will not be analyzed. Consequently, randomization and the planned parallel comparison describe the design, not a completed efficacy analysis. The record does not report how randomization was generated, how allocation was concealed, the intended allocation ratio, or the detailed treatment and assessment procedures.
The study is classified as phase NA. It is sponsored by Northwestern University. No statistical analysis plan or sample-size justification is reported in the registry record. The brief summary’s plan to recruit 20 subjects should not be treated as evidence that the trial had a documented power calculation.
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 | Ramelteon (TAK-375) 8mg Tablets | Placebo 8 mg Tablets |
|---|---|---|
| STARTED | 1 | 2 |
| COMPLETED | 1 | 2 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: We had difficulties with recruitment and did not manage to recruit enough participants so no data was collected and the study was terminated.
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 | Ramelteon (TAK-375) 8mg Tablets | Placebo 8 mg Tablets | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 2 | 3 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 2 | 3 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 57 (SD 0) | 57 (SD 7.85) | 57 (SD 7.85) |
| Sex: Female, Male: Female | Participants | 1 | 0 | 1 |
| Sex: Female, Male: Male | Participants | 0 | 2 | 2 |
| Region of Enrollment: United States | participants | 1 | 2 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Change in the Frequency of RBD Based on the Daily Sleep Diaries, Completed Daily for the Duration of the Study by the Study Subjects' Bed Partners/Caregivers, measured over 12 weeks.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was change in the frequency of RBD events, assessed through daily sleep diaries completed by participants’ bed partners or caregivers. The stated timeframe was 12 weeks. The diaries were intended to capture events in everyday sleep rather than relying only on a single assessment at a study visit. The endpoint therefore targets a symptom frequency that could vary over time and that may be observed by someone sharing the participant’s sleep environment.
As a general statistical concept, repeated diary entries can describe how an outcome changes during follow-up, but interpreting such data requires a clear definition of an event, consistent recording, and a specified method for combining observations. The registry record does not report the event definition, how diary completeness would be assessed, or how daily observations would be reduced to a participant-level endpoint. Those methods are not reported in the registry record.
The intended comparison was change in RBD frequency between the ramelteon and placebo groups. The endpoint is relevant to the study’s stated question because it measures the frequency of the behavior under investigation. However, the record states that no data were collected and that the study was terminated because of low enrollment and recruitment. There is therefore no reported endpoint value, group contrast, or estimate of uncertainty. The secondary measure of tonic muscle activity from baseline and final polysomnography is distinct from the diary-based primary outcome and cannot substitute for an unobserved primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that there is no efficacy result to interpret. The registry record states that no data were collected and that the primary outcome data will not be analyzed. It reports enrollment of 3 participants, but does not provide outcome observations or a treatment-effect estimate. Accordingly, no conclusion about the direction, magnitude, or precision of a ramelteon-placebo difference in RBD frequency can be drawn from this record.
The design planned randomization and a placebo comparison, which would ordinarily support an estimate of the effect of assignment to the study arms. But design features cannot replace observed endpoint data. Randomization does not itself demonstrate balance in a very small enrolled group, and the record does not report participant characteristics by arm. It also does not report treatment exposure, completion of follow-up, or diary availability.
The adverse-event figures describe the limited safety reporting, not efficacy. The registry lists 1 participant at risk for serious and other adverse events in the ramelteon group and 2 in the placebo group, with 0 affected in each group for both categories. These counts are small, and the record does not report deaths. The counts should be read as registry-reported events in this study, not as precise estimates of comparative risk.
In general, an effect estimate is more informative when accompanied by an uncertainty interval. A confidence interval describes a range of values compatible with the data under the statistical model; it does not guarantee that the true effect lies within that range. Here, no efficacy estimate or confidence interval is reported because the registry record says the outcome data were not collected or analyzed. There is no basis for interpreting a p-value, statistical significance, or clinical importance.
The record’s design summary mentions a planned recruitment target of 20, while actual enrollment was 3. This difference indicates that the intended scale of recruitment was not achieved, but it does not quantify an effect or establish why individual people did or did not participate. The stated reason for termination is low enrollment and recruitment difficulty. The result is a study that documents a research question and a planned comparison, but does not yield an analyzed answer to that question.
9. Statistical Methods Explained
The registry describes a randomized, parallel-group comparison of ramelteon and placebo. In general, random allocation is used to reduce systematic differences between groups at the point of assignment. It does not guarantee that groups will be similar on every characteristic, especially when enrollment is small. The registry record does not report the randomization sequence method, allocation concealment, or planned allocation ratio, so those aspects cannot be assessed.
What would a treatment-effect estimate represent?
For the stated primary outcome, an analysis would ordinarily compare change in RBD-event frequency between the assigned groups over the planned 12-week timeframe. The exact estimand—the precise treatment effect the analysis aims to describe—depends on choices such as how change is defined, which observations count, and how incomplete diaries or discontinued treatment are handled. These details are not reported in the registry record. More importantly, the record states that no outcome data were collected and that the data will not be analyzed. No treatment-effect estimate is available.
Why do uncertainty intervals matter?
As a general explanation, a confidence interval expresses uncertainty around an estimate under a specified statistical model and analysis procedure. A narrow interval generally indicates greater precision than a wide interval, while both the estimate and interval depend on the data and assumptions. An interval does not establish that an effect is clinically important, and it cannot be calculated meaningfully without an analyzed estimate and suitable data. The registry record reports no efficacy estimate or confidence interval.
A p-value, when used, measures how surprising data at least as incompatible with a null hypothesis would be under the assumptions of a particular test. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. No p-value or inferential analysis is reported for the primary outcome. The record explicitly states that data will not be analyzed, so statistical significance is not an appropriate interpretation of this study.
How should the planned sample-size note be read?
The sample-size assumptions describe a planning illustration using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They also describe an effect to detect as a stated fraction of an observed effect. Such assumptions can be used generally to illustrate how planning requirements depend on the target effect and statistical choices. A planning illustration is not an observed result, and a sample size associated with a power target is not observed power.
In this study, the registry record states that no data were collected and that efficacy data will not be analyzed. It therefore reports no trial-derived observed effect for the primary endpoint to anchor an observed-effect-based planning interpretation. No sample-size justification or protocol-based power calculation is reported in the registry record. The planned recruitment of 20 subjects is stated in the brief summary, but that number alone does not establish the assumptions or rationale behind the target.
What does over-dispersion mean in general?
For count outcomes such as event frequency, a statistical model may assume a particular relationship between the mean and variability. Over-dispersion occurs when the observed variability is greater than the model allows. If unaddressed, it can make uncertainty estimates too small and statistical evidence appear stronger than it is. This is a general consideration for event-count outcomes; the registry record does not report a count model, an assessment of over-dispersion, or any analysis of the diary outcome.
Repeated diary observations also raise general issues about dependence: entries from the same participant are not necessarily independent of one another. A suitable analysis would need to account for the repeated observations or define a participant-level summary, but the registry record does not specify an approach. The record also does not describe the statistical model for the secondary polysomnographic outcome.
Because the study did not produce an analyzed efficacy dataset, no model choice, diagnostic check, adjustment, or sensitivity analysis can be evaluated from the registry record. This is not evidence that a particular method was used or omitted in an unpublished analysis; the relevant methods are not reported in the registry record, which states that outcome data were not analyzed.
10. Multiplicity, Missing Data and Analysis Populations
The record identifies a primary diary-based outcome and a secondary outcome measuring tonic muscle activity from baseline and final polysomnography. It does not report an inferential analysis plan, a hierarchy of hypotheses, or a procedure for handling multiple comparisons. A multiplicity adjustment is therefore not reported in the registry record. Since the record also states that no data were collected and the outcome data will not be analyzed, there are no reported tests whose multiplicity can be evaluated.
Missing-data handling is also not reported. The record says no data were collected, but does not describe whether any partial diaries, incomplete assessments, or follow-up information existed. It gives no imputation method, missingness assumption, or sensitivity analysis. The absence of reported outcome data should not be replaced with an assumption that observations were missing at random or that a particular method would have been suitable.
The analysis population is not reported in the registry record. There is no statement about an intention-to-treat population, a per-protocol population, or another defined analysis set. The record does not report whether participants received assigned treatment or completed the planned follow-up. With enrollment of 3 and no collected efficacy data, no analysis population or endpoint denominator can be reconstructed from the reported efficacy information.
These omissions limit interpretation of how an efficacy analysis would have been conducted, but they do not change the key result status: no primary outcome analysis is available. Statistical procedures for multiplicity, missing data, and analysis populations cannot be inferred from the randomized design or from the outcome descriptions alone.
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 |
|---|---|---|---|
| Ramelteon (TAK-375) 8mg Tablets | 0 | 1 | 0.0% |
| Placebo 8 mg Tablets | 0 | 2 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ramelteon (TAK-375) 8mg Tablets | 0 of 1 |
| Placebo 8 mg Tablets | 0 of 2 |
The registry lists 1 participant at risk in the ramelteon group and 2 at risk in the placebo group for serious adverse events. It reports 0 serious adverse events in each group. For other adverse events, it likewise lists 1 at risk and 0 affected in the ramelteon group, and 2 at risk and 0 affected in the placebo group. The record does not report deaths.
These are small participant counts. In general, observing no reported events in a small group does not establish that the underlying risk is zero; the estimate would be imprecise, and events occurring outside the observed or recorded period may not be captured. The record does not describe adverse-event collection methods, exposure duration, or the period used for safety follow-up, so those details are not reported in the registry record.
The counts do not support a reliable comparison between arms. They should not be interpreted as showing that either intervention is safer, or as evidence that adverse events cannot occur. They are registry-reported counts among the listed participants at risk, alongside a study terminated for low enrollment and recruitment difficulties. The missing death count is not equivalent to a reported count of zero.
12. What the Result Does, and Does Not, Mean
The record establishes that investigators planned a randomized, placebo-controlled pilot study of ramelteon for RBD in people with parkinsonism. It specifies a daily sleep-diary measure of RBD-event frequency as the primary outcome, with a planned 12-week timeframe. It also identifies a secondary polysomnographic measure of tonic muscle activity. These details describe the study question and intended measurements.
The record does not establish an efficacy result. It reports actual enrollment of 3, states that recruitment difficulties led to termination, and explicitly says that no data were collected and the data will not be analyzed. There is no reported change in RBD frequency, no comparison between treatment groups, and no estimate of uncertainty. Therefore, the study cannot show from its posted results whether ramelteon changed the measured outcome relative to placebo, or by how much.
Likewise, the safety counts do not establish a comparative safety profile. The registry reports no serious or other adverse events among the small numbers listed as at risk, but those counts are too limited to characterize risk reliably. The record does not report deaths.
These findings should not be described as evidence of no treatment effect, nor as evidence of an effect. An unmeasured or unanalyzed outcome leaves the treatment question unanswered in this registry record. The termination is a recruitment outcome, not an efficacy finding. The trial’s randomized design is relevant to its intended method, but without collected and analyzed outcome data it does not provide a treatment-effect estimate.
The record can still be informative about feasibility: the planned recruitment target was 20, whereas enrollment was 3, and low enrollment and recruitment were cited as the reason for termination. It does not report the causes of recruitment difficulty in detail or establish which changes might have enabled completion. Any broader claim about the intervention, the disease population, or clinical practice would go beyond the results reported in this record.
13. Why This Trial Matters Statistically
This study is statistically instructive because it separates a planned design from an analyzable result. Randomization, masking, a comparator, and defined outcomes describe how a trial is intended to answer a question. They do not produce evidence about the treatment contrast unless outcome data are collected and analyzed. Here, the registry record documents a structured question but explicitly reports no collected efficacy data.
The recruitment experience also matters for interpretation. The brief summary planned recruitment of 20 subjects, while the record reports enrollment of 3 and termination due to low enrollment and recruitment. A trial that cannot recruit its intended population may not reach the stage at which its central statistical question can be estimated. This is distinct from an inconclusive estimate with a wide confidence interval: the registry reports no efficacy estimate at all.
The record illustrates why numerical results need context. The adverse-event counts are stated for the enrolled participants, but the small numbers cannot support a precise comparison. Likewise, a sample-size planning illustration is not a substitute for observed outcomes and is not evidence of observed power. The planning note refers to an observed effect, while the efficacy record states that no data were collected; no trial-derived efficacy effect is available in the posted results.
For clinical researchers, the distinction between a completed analysis and a terminated study is essential. A null finding would require analyzed data and an estimate compatible with little or no difference; this record does not report such an estimate. The appropriate statistical reading is that the intended comparison remains unanswered in the registry record, rather than that the intervention did or did not affect the endpoint.
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 principal limitation is that the registry record reports no collected efficacy data and no analysis. The primary diary-based endpoint therefore has no reported values, treatment contrast, or measure of precision. The secondary polysomnographic outcome also has no reported result. The study’s termination after enrollment of 3 leaves the planned treatment question unanswered.
Recruitment was substantially below the planned 20 subjects described in the brief summary. The record attributes termination to low enrollment and recruitment difficulties, but does not provide further information about screening, reasons for non-enrollment, or barriers to participation. Generalizability cannot be evaluated from outcome data that were not collected, and participant characteristics by group are not reported.
The registry record does not report randomization procedures, allocation concealment, masking details, treatment adherence, follow-up completion, diary completeness, or the definition and analysis of an RBD event. It also does not report missing-data methods, analysis populations, a statistical analysis plan, or a sample-size justification. These gaps prevent assessment of how the proposed efficacy analysis would have addressed key design and measurement issues.
The safety counts are based on 1 participant at risk in the ramelteon group and 2 in the placebo group. Such limited counts cannot characterize uncommon events or support a stable comparison, and deaths are not reported. These limitations are specific to the small enrollment and the lack of collected outcome data; they should not be mistaken for evidence that outcomes were measured and found unchanged.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Tolerability of Ramelteon in Patients With Rapid Eye Movement (REM) Behavior Disorder and Parkinsonism — NCT00745030.
- Registry record last updated 2024-01-09; status last verified 2023-12.
- Results first posted 2010-11-10.
- 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
This registry record describes a randomized, parallel-group, placebo-controlled pilot study of ramelteon for RBD in people with parkinsonism. The listed masking designation is quadruple, while the official title describes the study as double blind; the masking details are not reported. Ramelteon 8mg tablets were compared with placebo 8 mg tablets. The primary outcome was change in RBD-event frequency from daily sleep diaries over 12 weeks, and the secondary outcome concerned tonic muscle activity measured by polysomnography.
The brief summary planned recruitment of 20 subjects. The record reports enrollment of 3 and status as terminated, citing low enrollment and recruitment difficulties. It states that no data were collected and that the primary outcome data will not be analyzed. No efficacy estimate or analysis is reported. Serious and other adverse-event counts were 0 in both groups, among 1 participant at risk in the ramelteon group and 2 in the placebo group; deaths are not reported.