Assess the Effect of Zolpidem, Silenor & Placebo on Arousability, Ataxia/Balance & Cognition in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assess the Effect of Zolpidem, Silenor & Placebo on Arousability, Ataxia/Balance & Cognition in Healthy Volunteers (NCT02353299), a randomized phase 4 study. The primary outcome is Auditory Arousal Threshold (AAT) at T-max.

2. Clinical Question

The primary outcome concerns arousability under a specific laboratory test, rather than a broad measure of sleep or daytime functioning. The study also recorded walking, balance, memory, and adverse-event outcomes. Those additional measures can provide context about performance on the tested tasks, but they do not change what the primary outcome measures.

The posted comparisons are between the Silenor 6 mg condition and placebo at 4 hours, and between zolpidem 10 mg and placebo at 1.5 hours. The registry lists a crossover design, so the same volunteers could contribute observations under different conditions. The registry record does not describe treatment sequence, washout procedures, or whether the posted comparisons account for within-person pairing. Those details matter when judging how the comparisons were analyzed.

3. Trial Design

This completed Phase IV study is listed as randomized, double-blind, placebo-controlled, and crossover. The registry gives enrollment as 52 and describes the participants as normal healthy adult male volunteers. Its study title refers to a four-way crossover study, with Silenor 6 mg, zolpidem 10 mg, and matching placebo conditions. The posted arm descriptions distinguish a placebo assessment at 4 hours from a placebo assessment at 1.5 hours.

The treatment conditions were a single nighttime dose of Silenor 6 mg or zolpidem 10 mg, with assessments timed to the stated T-max for the relevant treatment. AAT assessments for Silenor and its matching placebo were conducted at 4 hours post dose; assessments for zolpidem and its matching placebo were conducted at 1.5 hours post dose. The registry record does not report the treatment sequence, washout interval, or other operational details of the crossover.

Randomization is intended to reduce systematic differences in treatment assignment, while double masking is intended to limit the influence of treatment knowledge on participants and study personnel. The registry record does not explain how masking was maintained or whether it was assessed. Placebo conditions provide the relevant comparison at the corresponding assessment time, but the two active-treatment comparisons occur at different times after dosing and should be read as separate comparisons.

The primary outcome is continuous: mean auditory arousal threshold in decibels, with standard deviation as the measure of spread. Secondary outcomes include walking, balance, memory, and adverse-event measures. Although the registry reports that the study is completed, detailed protocol information, the original statistical analysis plan, and the trial's own sample-size justification are not reported in the registry record.

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.

First Intervention (1 Night)

Second Intervention (1 Night)

Third Intervention (1 Night)

Fourth Intervention (1 Night)

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.

Population: Subjects were healthy males

6. Primary Endpoint

The registry lists the primary outcome as Auditory Arousal Threshold (AAT) at T-max, measured over at either 1.5 or 4 hours post dose.

The primary endpoint is auditory arousal threshold (AAT) at T-max, recorded in decibels. The registry describes presenting a 1000 Hz tone through audiometric earphones. The tone began at 30 dB and increased by 5 dB until the participant woke or the maximum level of 110 dB was reached. The outcome is therefore a threshold measured during a defined auditory arousal test, not a general rating of sleep quality or a direct measure of everyday alertness.

A higher threshold means that a louder tone was needed to produce waking during the test, or that the participant reached a higher level before waking. That makes the measure relevant to the study's question about arousability after nighttime administration. Because the assessment is tied to a specified time after each dose, the results describe performance under those timing and testing conditions.

The registry reports group means and standard deviations. A mean describes the average threshold within an arm; a standard deviation describes variation among the observations in that arm. Neither measure alone describes the full distribution or explains individual responses. The record does not report a clinically meaningful threshold difference, a validated cutoff, or how AAT relates to real-world outcomes. Interpretation should therefore remain focused on the measured auditory test and its posted comparisons.

7. Results Posted in the Registry

• Silenor 6 mg (DXP-4H): mean 85.20 versus 78.00 on control; difference 7.20 (95% CI 1.20 to 13.20), standardized effect d = 0.46; z-test p = 0.019.
• Zolpidem 10 mg (ZOL-1.5H): mean 103.20 versus 78.00 on control; difference 25.20 (95% CI 19.21 to 31.19), standardized effect d = 1.62; z-test p = <0.001.
• Placebo (PBO-1.5H): mean 84.70 versus 78.00 on control; difference 6.70 (95% CI -0.17 to 13.57), standardized effect d = 0.38; z-test p = 0.056.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Tandem Walk Step-Offs

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Silenor 6 mg (DXP-4H): mean 1.50 versus 0.90 on control; difference 0.60 (95% CI -0.16 to 1.36), standardized effect d = 0.31; z-test p = 0.122.
  • Zolpidem 10 mg (ZOL-1.5H): mean 8.10 versus 0.90 on control; difference 7.20 (95% CI 4.99 to 9.41), standardized effect d = 1.25; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Silenor 6 mg (DXP-4H) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Zolpidem 10 mg (ZOL-1.5H) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Tandem Walk Duration Over Five Trials

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Silenor 6 mg (DXP-4H): mean 4.97 versus 4.82 on control; difference 0.15 (95% CI -0.48 to 0.78), standardized effect d = 0.09; z-test p = 0.640.
  • Zolpidem 10 mg (ZOL-1.5H): mean 6.69 versus 4.82 on control; difference 1.87 (95% CI 1.03 to 2.71), standardized effect d = 0.85; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Silenor 6 mg (DXP-4H) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Zolpidem 10 mg (ZOL-1.5H) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Berg Balance Test

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Silenor 6 mg (DXP-4H): mean 54.50 versus 55.10 on control; difference -0.60 (95% CI -1.25 to 0.05), standardized effect d = -0.36; z-test p = 0.068.
  • Zolpidem 10 mg (ZOL-1.5H): mean 51.40 versus 55.10 on control; difference -3.70 (95% CI -4.93 to -2.47), standardized effect d = -1.16; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Silenor 6 mg (DXP-4H) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Zolpidem 10 mg (ZOL-1.5H) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary results cover several kinds of performance: tandem walking, balance, memory, and adverse events. Across the posted continuous measures, the pattern is not uniform across treatments or endpoints. Zolpidem comparisons show more marked differences from the corresponding placebo reference on several posted walking and balance measures, while the Silenor comparisons are less consistent and include estimates with intervals spanning zero. This broad pattern offers context, but it is not a single combined measure of function.

The secondary findings are related to the primary result in that they examine other outcomes after the same nighttime treatment conditions. They do not measure AAT, however, and they should not be treated as confirmation of the primary endpoint. Each task has its own scale, variability, and interpretation. The registry record does not provide a common threshold for meaningful change across these outcomes. Numerical results for the named memory tasks are not reported in the registry record.

Unadjusted secondary results carry less weight because several outcomes and contrasts are considered, and no multiplicity strategy is reported. A small p-value from an isolated secondary comparison can arise by chance when many analyses are examined. Conversely, an interval spanning zero does not prove that there is no difference; it reflects uncertainty under the particular calculation. The registry also lists no reported analyses for the secondary outcomes, so the posted recalculations do not replace a prespecified model-based analysis.

The crossover design makes the relationship among within-participant observations important for interpreting these findings. Arm-level summaries alone do not show how each person's results changed across conditions. In addition, assessment timing differs between treatment comparisons, and the placebo conditions are correspondingly timed. The secondary results are best read as outcome-specific, exploratory context for the study's stated performance questions, rather than as independent proof of broad or lasting effects.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Tandem Walk Step-Offs
• Tandem Walk Duration Over Five Trials
• Berg Balance Test
• Immediate Free Recall Task
• Delayed Free Recall Task
• Number of Participants With Adverse Events

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous, so its arm summaries are means and standard deviations. A mean gives the arithmetic average of the recorded AAT values in an arm. A standard deviation describes how spread out individual measurements are around that average. It is not the same as the uncertainty around the mean: the latter also depends on how many observations contribute and on the analysis used.

The displayed mean differences compare each listed arm with its specified placebo reference. A positive difference means the active-arm mean is higher than the reference mean in the Silenor and zolpidem comparisons. For the placebo-at-1.5-hours comparison, the estimate describes the difference from the placebo-at-4-hours reference. These are contrasts of averages, not descriptions of how every participant responded.

The intervals give a range of values compatible with the estimated contrast under the calculation's assumptions. An interval that includes zero does not establish a clear direction of difference at the interval's associated confidence level; an interval excluding zero indicates that zero is outside that range. The confidence level for the posted intervals is not reported in the registry record, so it should not be inferred from the interval endpoints alone. Intervals also do not tell whether a difference is clinically important.

The p-values express how inconsistent the data are with a specified null model, conditional on the assumptions of the analysis. They are not the probability that the null hypothesis is true, and they do not quantify the size or importance of an effect. The displayed primary-comparison p-values are unadjusted. The registry record does not report a multiplicity adjustment, a prespecified testing hierarchy, or the full statistical model behind sponsor analyses.

The registry identifies the trial as a crossover study. In a crossover design, participants receive more than one condition over time, and comparisons can use the fact that each person serves as their own control. This can be informative because stable differences between people are less influential in a within-person comparison. However, measurements from the same participant are generally related. The degree of that relationship affects the uncertainty of a paired contrast. The posted recalculations use arm-level summary statistics and are labeled unadjusted; the registry record does not report the within-person covariance or say that pairing was used in these calculations. For that reason, the recalculated intervals and p-values should not be treated as a full crossover analysis.

The term unadjusted also matters because the study has multiple outcomes and contrasts. When many hypotheses are examined, the chance of obtaining an apparently notable result somewhere among them can increase. A suitable approach depends on the planned objectives and analysis hierarchy. The registry record does not report whether a correction, gatekeeping procedure, or other multiplicity strategy was planned or applied. Without that information, individual secondary p-values carry less weight than they would under a fully described confirmatory analysis.

The secondary outcomes include continuous measures such as tandem walk step-offs, tandem walk duration, and Berg Balance Test score, as well as memory tasks and adverse-event counts. Means and standard deviations summarize continuous measures, but their interpretation depends on each measure's scale and direction. A difference in a score is not automatically a difference of clinical importance. The memory outcomes are named in the registry, but corresponding numerical summaries are not included in the posted secondary results described for this record. Their results are therefore not reported in the registry record.

Standard deviations are especially relevant when outcome distributions are uneven or contain unusually large values. For a continuous outcome with a strongly skewed distribution, the mean and standard deviation may not capture the typical participant's result well. For count-like measures such as step-offs, observations may cluster near small values while some participants have much larger counts. General statistical practice may use models or summaries suited to such distributions, but the registry record does not report distributional checks, transformations, or model choices. No specific alternative analysis can be attributed to this trial.

The posted safety information separates serious adverse events, other adverse events, and deaths. These are different categories and should not be conflated. The arm-level counts indicate how many participants were at risk and how many were affected according to the registry summary. The record does not provide event descriptions for serious events because none are listed, nor does it provide details about event timing, severity grades, or attribution beyond the posted categories.

Finally, sample-size illustrations based on observed effects are planning calculations, not evidence about the trial's original design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect set to a stated fraction of the observed effect. The trial's own design assumptions and sample-size justification are not reported in the registry record. Those planning calculations should not be confused with the analysis of the completed study.

11. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimate. For the primary comparisons, the recalculated interval for Silenor versus the 4-hour placebo condition runs from 1.196 to 13.2 dB around a mean difference of 7.2 dB. The interval for zolpidem versus the 1.5-hour placebo condition runs from 19.21 to 31.19 dB around a mean difference of 25.2 dB. The interval for the comparison between the two placebo assessment times runs from -0.167 to 13.57 dB around a mean difference of 6.7 dB.

The interval endpoints communicate a range of uncertainty, not a set of values that each has an individual probability of being the true difference. The confidence level is not reported in the registry record. The interpretation also depends on the assumptions behind the recalculation, including how the crossover structure and within-participant dependence are handled. The registry does not report those details for these recalculated comparisons.

The first two primary intervals exclude zero, while the placebo-time comparison interval includes zero. This describes the location of zero relative to the recalculated intervals; it does not settle clinical importance or correct for the number of comparisons. The width of an interval reflects both variability and the amount of information available, but it cannot be interpreted independently of the analysis method.

The arm standard deviations also show that measurements varied within each condition. For example, the posted AAT standard deviations are 11.8 for Silenor at 4 hours, 18.6 for its placebo condition, 11.8 for zolpidem at 1.5 hours, and 17.1 for its placebo condition. These summaries help describe within-arm spread, but they do not reveal the paired differences for participants in a crossover study. The registry record does not report a confidence interval from a sponsor crossover model or the confidence level for the recalculated intervals.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for 80% power and participants per arm for 90% power; they are not total event counts. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is the stated fraction of the observed effect. The trial's original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives an illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the calculation's assumptions, if that effect and those assumptions were correct. The 90% power column uses a higher target probability of detection and consequently requires more participants per arm for the same effect. These are planning concepts, not guarantees about a future study.

Rows using 100% of the observed effect use the observed contrast as the target for the illustration. Rows using 75% or 50% of the observed effect represent smaller target differences. Smaller effects are harder to distinguish from random variation and therefore require more participants. The listed results are sensitive to the observed effect: estimates from a completed study can be unstable, and planning a later study around an optimistic effect can produce an inadequate design if the true effect is smaller.

These figures are not observed power. They do not measure the probability that the completed trial detected an effect, and they do not replace an analysis of its uncertainty. The calculations are simple planning illustrations based on arm-level summaries; they do not describe the trial's original design or account for crossover-specific information unless such details are included in the calculation. The registry record does not report the original sample-size rationale or the assumptions used to plan enrollment.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 7.200; pooled standard deviation σ = 15.608.
2. n = 2 × (1.96 + 0.842)² × 15.608² / 7.200² = 73.8, rounded up to 74 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 7.2                      # observed difference in means
sigma <- 15.6084389461802                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2353299)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 74 (80% power), 99 (90% power)
 75% of observed effect: n per arm = 132 (80% power), 176 (90% power)
 50% of observed effect: n per arm = 296 (80% power), 396 (90% power)
power.t.test: 74.7 
Simulated power at n = 74 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity plan for the primary or secondary outcomes. It does not state whether one contrast was designated as the sole confirmatory test, whether tests were ordered hierarchically, or whether p-values were adjusted to account for multiple comparisons. The posted p-values are described as unadjusted recalculations. Without a reported plan, their role in formal inference is uncertain, particularly for secondary outcomes.

Missing-data handling is also not reported in the registry record. The posted arm summaries include the number contributing to each measure, but the record does not describe why the available counts differ between some arms, whether measurements were missing, or how any missing observations were handled. It does not report imputation, sensitivity analyses, or rules for excluding incomplete records. The reason for any difference in analyzed counts is not reported in the registry record.

The analysis population is not described. The record does not say whether results are based on all randomized participants, participants who completed every treatment period, or another defined population. Nor does it report how withdrawals, protocol deviations, or incomplete crossover sequences were treated. These details matter because exclusions after randomization can affect the comparability that randomization is intended to support.

The registry identifies a crossover design but does not report a model that accounts for treatment sequence, period, carryover, or within-participant correlation. These are considerations in crossover analyses, not claims about what occurred in this trial. The registry record does not report whether they were assessed or how they were handled. The absence of these details limits assessment of the posted estimates and their uncertainty.

The record also does not report an analysis plan or sponsor-reported statistical analyses. As a result, it is not possible to determine from the registry whether the displayed outcomes, contrasts, and analysis choices were prespecified, or whether additional analyses were conducted but not posted. These omissions do not establish that an analysis was not performed; they mean that it is not reported in the registry record.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists zero serious adverse events in each of the four treatment conditions and zero deaths in each condition. The numbers at risk are 51 for Silenor 6 mg at 4 hours and 52 for each of the other listed conditions. These are the posted arm-level figures. The registry record does not provide descriptions of serious events, and no serious-event terms are listed.

Other adverse events are recorded separately from serious adverse events. The posted affected-participant counts are 13 for Silenor 6 mg, 11 for placebo at 4 hours, 12 for zolpidem 10 mg, and 10 for placebo at 1.5 hours. These counts should not be confused with serious events or deaths. The registry record does not provide event-level details, timing, severity, or treatment attribution for these other events.

These figures describe what was recorded in the study conditions; they do not establish comparative safety. The crossover structure and the registry's lack of event-level information limit interpretation of the counts. The absence of listed serious events does not establish the absence of all possible harms, particularly outside the study's population, observation conditions, and reported record.

16. What the Result Does, and Does Not, Mean

The results describe auditory arousal thresholds and selected performance measures among healthy volunteers after a single nighttime administration of the study treatments, assessed at the stated post-dose times. The primary summaries show higher mean AAT values in the active-treatment conditions than in their respective placebo conditions. The recalculated differences and intervals quantify those posted arm-level contrasts, subject to the limitations of unadjusted calculations and unreported crossover analysis details.

These findings do not show how the treatments affect people with a sleep disorder or other health conditions. The registry describes healthy male volunteers, and the results cannot be assumed to apply to populations not studied. They also do not establish what happens at other doses, after repeated administration, at other assessment times, or in settings outside the laboratory tests described in the registry.

AAT is a response to a controlled auditory stimulus. It is not interchangeable with a measure of daily functioning, driving, decision-making, sleep quality, or overall cognitive performance. The other posted outcomes measure particular walking, balance, and memory tasks; they do not provide a complete account of functioning. The record does not report a threshold for clinical importance or a link between the measured changes and meaningful outcomes outside the tests.

The statistical estimates also have limits. The recalculated comparisons are unadjusted, and the registry does not report whether the within-person structure of the crossover was incorporated. The confidence level for the displayed intervals and the multiplicity strategy are not reported in the registry record. Thus, the results should be read as descriptions of posted data, not as definitive evidence for broad conclusions about benefit, harm, or clinical use.

The serious-event and other adverse-event summaries provide a limited account of safety observations. They do not establish the absence of risk, nor do they support a complete comparison of safety without event-level detail and a reported analysis. The meaning of the trial is therefore narrow: it documents outcomes under specific conditions in a defined volunteer population, with important analysis and reporting details unavailable in the registry record.

17. Why This Trial Matters Statistically

This trial illustrates why the design and analysis structure matter as much as the observed arm means. A crossover design can make within-person comparisons useful, because each participant can experience multiple conditions. At the same time, that design calls for an analysis that recognizes related measurements from the same participant. Arm-level summaries alone do not convey the paired changes or the correlation needed to evaluate a crossover contrast fully.

The trial also demonstrates the difference between a statistically detectable contrast and a result with established practical importance. The AAT estimates include intervals and p-values, but the registry does not define a meaningful threshold or connect the laboratory measure to broader functioning. Those distinctions help prevent a p-value from being treated as a complete account of the result.

Multiple endpoints add another interpretive challenge. A study can assess arousability alongside walking, balance, memory, and adverse events, but the more outcomes and comparisons considered, the more important it is to know the prespecified analysis plan and multiplicity strategy. Those details are not reported in the registry record. Secondary signals should therefore be considered in context rather than treated as stand-alone confirmation.

Finally, the record offers an example of why planning figures based on observed effects must be kept separate from a trial's actual design rationale. The illustrative calculations can help readers understand how target effect size and desired power influence planning, but they do not reveal the assumptions used when this study was designed. Transparent reporting of those assumptions, the crossover model, missing-data handling, and analysis populations would make the statistical evidence easier to assess.

18. 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.

Several limitations are specific to the information available for this study. The registry describes healthy adult male volunteers, so the results do not directly characterize other populations. The assessment times are tied to the treatment conditions: Silenor and its placebo were assessed at 4 hours, while zolpidem and its placebo were assessed at 1.5 hours. Comparisons across active treatments therefore do not isolate treatment differences at a common assessment time.

The registry identifies a crossover design but does not report treatment sequence, washout procedures, period effects, carryover assessment, or the method used to account for within-participant correlation. These omissions are important for judging how the posted arm summaries relate to the design. The recalculated estimates are unadjusted calculations from summary statistics, not a reported crossover model.

The registry record does not report the statistical analysis plan, multiplicity handling, analysis populations, missing-data approach, or the original sample-size justification. It also does not report a confidence level for the recalculated intervals or a threshold for clinically meaningful differences. Numerical results for the named memory tasks are not reported in the registry record.

The primary test is a controlled auditory arousal task, and the other measures are specific laboratory performance tasks. The registry does not report how these outcomes correspond to everyday functioning or longer-term outcomes. Finally, the safety summaries lack event-level descriptions and details about timing, severity, and attribution. These reporting gaps constrain interpretation even though the study is listed as completed.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Assess the Effect of Zolpidem, Silenor & Placebo on Arousability, Ataxia/Balance & Cognition in Healthy Volunteers — NCT02353299.
• Registry record last updated 2018-01-02; status last verified 2017-12.
• Results first posted 2017-12-07.
• 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.

22. Record Summary

NCT02353299 is a completed Phase IV, randomized, double-blind, placebo-controlled crossover study sponsored by Currax Pharmaceuticals. The registry lists enrollment of 52 and describes normal healthy adult male volunteers. The study assessed single nighttime doses of Silenor 6 mg and zolpidem 10 mg against matching placebo conditions, with AAT assessment at 4 hours for Silenor and its placebo, and at 1.5 hours for zolpidem and its placebo.

The primary outcome was mean auditory arousal threshold in decibels. The posted arm summaries include walking and balance outcomes, while memory outcome results are not reported in the registry record. The record lists zero serious adverse events and zero deaths in each treatment condition. Details of the crossover analysis, missing-data approach, multiplicity handling, and original sample-size rationale are not reported in the registry record.