Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet (NCT01106859), a randomized phase 1 study. The primary outcome is Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold.

2. Clinical Question

The study asked a focused performance question: whether highway-driving lane-position variability after middle-of-the-night zolpidem differed from placebo according to a specified threshold. It also included a bedtime zopiclone condition, allowing the registry to describe driving performance after that treatment condition in the same trial framework. The record lists insomnia as the condition, but the participants are described as healthy adult volunteers rather than people being treated for insomnia.

The primary outcome is a categorized comparison with placebo, not simply a mean SDLP value. Its categories are intended to distinguish performance that is worse, neutral, or improved relative to placebo according to the 2.5 cm threshold. The registry record does not report the number of participants in any of those categories, so it does not establish from the listed endpoint information how the treatment conditions compared.

The trial also names other driving and safety outcomes, including mean SDLP, mean standard deviation of speed, treatment-emergent adverse experiences, and outcomes using other SDLP thresholds. Their numerical results are not reported in the registry record. The clinical question therefore needs to be kept distinct from the missing result: the registry describes what was assessed, but the primary category counts and the supporting outcome estimates are not reported in the registry record.

3. Trial Design

This is a completed Phase 1, randomized, triple-masked, placebo-controlled, four-way crossover study. The official title describes it as double-blind, while the registry design fields classify masking as triple. It was single-center and enrolled 40 healthy adult volunteers. The registry lists the study start as 2010-06 and primary completion as 2010-09.

The four treatment conditions were zolpidem 3 hours before driving, zolpidem 4 hours before driving, zopiclone at bedtime 9 hours before driving, and placebo. In the zolpidem conditions, a placebo matching zopiclone was taken at bedtime. In the zopiclone condition, a placebo matching zolpidem was taken in the middle of the night. The placebo condition used a placebo matching zopiclone at bedtime and a matching zolpidem placebo in the middle of the night. These matching treatments are described in the registry to clarify how the conditions were masked.

A crossover design compares treatments within a participant across treatment conditions, rather than relying only on comparisons between separate parallel groups. This general feature can make within-participant contrasts informative because each participant may serve as their own reference. The registry record does not report treatment sequence details, the interval between treatment periods, or how period and sequence effects were addressed. Those details matter when interpreting any crossover analysis, but cannot be inferred from the design label alone.

The primary outcome timeframe is 3-9 hours post dose. SDLP was assessed during a highway driving test, with the car's lateral position relative to the left lane boundary recorded by an infrared camera mounted on the roof. The registry lists an intent-to-treat population for the primary endpoint. Further detail on participant flow, adherence, and the number contributing data to each treatment comparison is 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.

Before assignment: Forty-four candidates were screened. Four screening failures: high blood pressure (2), positive drug test (1), personal reasons (1)

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent to treat population

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold, measured over 3-9 hours post dose.

The primary endpoint is the number of participants whose standard deviation of lateral position, or SDLP, after active treatment was classified relative to placebo using a 2.5 cm threshold. SDLP describes variability in the car's lateral position during the highway driving test. The registry says lateral position was recorded relative to the left lane boundary using an infrared camera mounted on the car's roof. The assessment timeframe is 3-9 hours post dose.

The registry describes the endpoint as three categories: worse, neutral, and improved. It defines worse as a difference in SDLP greater than 2.5 cm and improved as a difference less than -2.5 cm. Its description of neutral says the difference is greater than or equal to 2.5 cm and less than or equal to -2.5 cm. Those two bounds cannot both hold for the same value, so the neutral-category wording appears internally inconsistent. The record does not clarify the intended definition.

In general, a threshold-based endpoint can make an average measurement easier to interpret in terms of a prespecified amount of change. It also discards information: participants with different measurements may be grouped together if they fall on the same side of a threshold. The registry record does not report the category counts, so neither the direction nor the precision of the primary outcome comparison can be assessed from the endpoint description alone. The threshold's clinical interpretation is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record gives the design labels and endpoint definitions, but it does not report a complete statistical analysis plan. The explanations below describe general statistical concepts and distinguish them from methods actually documented for this trial.

What does a crossover design compare?

In general, a crossover study compares outcomes under different treatment conditions within the same participants. This can reduce the influence of stable differences between participants, because a participant's outcome under one condition can be contrasted with that participant's outcome under another. The benefit depends on the validity of the design and analysis. Treatment order, time between periods, and the possibility that one treatment affects outcomes in a later period can all matter. The registry identifies a randomized four-way crossover design, but the sequence and period details and the method for accounting for them are not reported in the registry record.

Randomization is intended to help prevent systematic differences in treatment assignment. Masking is intended to reduce the influence of expectations or knowledge of treatment assignment on participants, study staff, or outcome assessment. The registry classifies masking as triple and the official title calls the study double-blind. It does not specify in the record which roles were masked, so the difference in labels cannot be resolved from the information reported.

What does SDLP measure?

SDLP is the standard deviation of lateral position during the highway driving test. In general, a standard deviation describes the degree of variation around an average. In this trial, the lateral position of the car relative to the left lane boundary was recorded by an infrared camera mounted on the car's roof. Greater variability in lane position is the kind of driving-performance measure the endpoint focuses on; the registry does not report a numerical result or a clinical interpretation for the observed values.

The primary endpoint converts a difference in SDLP relative to placebo into categories using a 2.5 cm threshold. Thresholds can simplify interpretation by marking a boundary for categorization, but categorization loses some detail compared with retaining the underlying continuous measurements. The registry's neutral-category definition gives two incompatible bounds: a difference at least 2.5 cm and at most -2.5 cm. The record does not explain whether one sign or bound was entered incorrectly, so that category should not be reinterpreted or repaired without clarification.

How should counts and means be distinguished?

The primary outcome is a count of participants in categories. It differs from a mean SDLP outcome, which would summarize a continuous measurement. A categorical count can show how many participants crossed a chosen threshold, while a mean can describe the average measurement across participants. Neither form is inherently sufficient on its own: the interpretation depends on the endpoint definition, the treatment contrast, the analysis population, and the uncertainty around the estimate. The registry lists secondary outcomes for both mean SDLP and SDLP-threshold comparisons, but their numerical results are not reported in the registry record.

For binary outcomes in general, an effect estimate may compare the chance of an event between treatment conditions. In a crossover trial, however, repeated treatment observations on the same participant are related; treating each condition as if it came from a separate independent group can misrepresent uncertainty. The appropriate analysis depends on the design and data structure. The registry record does not report a model or other analysis method for the primary category endpoint, so no particular binary model should be attributed to this study.

What do uncertainty measures tell a reader?

In general, a confidence interval expresses uncertainty around an estimated effect under the chosen model and assumptions. A narrow interval indicates greater precision than a wide interval, but neither width nor statistical significance alone establishes clinical importance. A p-value, in general, describes how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It is not the probability that the null hypothesis is true. No confidence intervals or p-values for the primary driving outcome are reported in the registry record.

Over-dispersion is a general issue for count outcomes when observed variability exceeds what a simple count model expects. If present, a model that assumes too little variation can produce uncertainty estimates that are too small. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not identify an outcome model or report a dispersion assessment, so it is not possible to say whether this issue arose in the trial analysis.

What do planning assumptions mean?

The registry describes planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning assumptions rather than observed trial results. The record says that time-to-event planning tables give the total number of events and other planning tables give participants per arm. These illustrations are not observed power, and they should not be read as the trial's own design justification. The trial's sample-size rationale is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures and 15 analyses. The named outcomes cover multiple aspects of driving performance and safety, including mean SDLP, mean standard deviation of speed, treatment-emergent adverse experiences, and SDLP comparisons using several thresholds. Examining multiple outcomes or contrasts can increase the chance that at least one result appears notable by chance. In general, multiplicity procedures can control or otherwise address this issue, but the appropriate approach depends on which outcomes and comparisons were planned and how they relate to the study question.

The statistical plan for multiplicity, including whether any adjustment was used or which analysis was designated for confirmatory interpretation, is not reported in the registry record. The record identifies a primary outcome, but its category results are not reported in the registry record. The listed secondary outcomes likewise do not include numerical results in the information recorded. It is therefore not possible to assess the pattern of estimates or the effect of any multiplicity procedure.

The primary outcome population is described as intent to treat. The registry record does not explain how that population was defined for a crossover study, how missing driving-test observations were handled, or how many participants contributed usable data to each endpoint or treatment comparison. Reasons for missing data and any imputation or sensitivity analyses are not reported in the registry record.

In general, missingness can affect interpretation when participants without observed outcomes differ from those with observed outcomes, or when missingness relates to treatment or performance. A stated intent-to-treat population does not by itself explain how absent measurements were handled. Details on treatment sequence, period effects, and the analysis population for secondary outcomes are also not reported in the registry record. Those omissions limit assessment of both the analysis and the reliability of any treatment comparison.

11. Safety Results

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

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 adverse-event record lists 40 participants at risk in each treatment condition. It reports 0 serious adverse experiences in the zolpidem 4 Hours Prior condition, 0 in the zolpidem 3 Hours Prior condition, 0 in the zopiclone condition, and 0 in the placebo condition. These are the serious-event counts recorded for this study. Death counts are not reported in the registry record.

The registry separately lists non-serious treatment-emergent adverse experiences: 5 for zolpidem 4 Hours Prior, 5 for zolpidem 3 Hours Prior, 6 for zopiclone, and 4 for placebo. These counts should not be confused with serious-event counts. The registry does not provide event terms or further detail on severity and timing in the listed safety information.

In general, zero observed serious events in a study does not establish that the underlying risk is zero. A safety count also does not establish that two treatments have equivalent safety, particularly without an uncertainty estimate and sufficient information about the study's duration and follow-up. The record is a crossover trial, so the listed treatment conditions should not be interpreted as four independent parallel groups. The safety counts describe what the registry reports; they do not, by themselves, answer the driving-performance question.

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

This record describes a controlled study of next-morning highway-driving performance after middle-of-the-night zolpidem dosing. Its design includes zolpidem given 3 hours or 4 hours before driving, a bedtime zopiclone condition, and placebo. The primary endpoint is a count-based classification of SDLP relative to placebo at a 2.5 cm threshold. These details establish the question and measurement framework, not the direction or size of the findings.

The numerical results for the primary endpoint are not reported in the registry record. The registry also does not report numerical results for the listed mean driving outcomes or SDLP-threshold secondary outcomes. Consequently, the treatment conditions cannot be ranked by driving performance from the recorded endpoint descriptions, and no claim about the size or precision of a treatment difference is supported by the information reported.

The record reports zero serious adverse experiences in each listed condition and gives non-serious adverse-event counts. Those safety observations apply to the study as recorded; they do not establish that serious events cannot occur or that treatments are equivalent in safety. The participant group is described as healthy adult volunteers, so the record does not establish how the findings would apply to other populations.

In general, a trial result is interpreted in light of its outcome definition, analysis, uncertainty, missing data, and design. Here, the primary endpoint wording for the neutral category is internally inconsistent, and the analysis details needed to assess the crossover comparisons are not reported in the registry record. The registry record therefore supports a description of the trial's design, intended measurements, and recorded safety counts, but it does not support a conclusion about the primary driving-performance result.

13. Why This Trial Matters Statistically

This study is statistically notable for pairing a within-participant crossover framework with a threshold-based driving-performance endpoint. A crossover design can offer a direct way to compare treatment conditions within participants, while the threshold endpoint attempts to translate continuous lane-position variability into categories relative to placebo. Each choice has interpretive consequences: crossover analyses need to account for repeated observations, and thresholding can obscure variation among participants within a category.

The registry also names multiple outcomes and analyses, spanning continuous driving measures, threshold comparisons, and adverse experiences. That breadth makes the prespecified analysis plan and multiplicity strategy important for interpreting any collection of results. Neither is described in the registry record. The absence of numerical primary outcome results is especially consequential because the trial's central comparison cannot be evaluated from its endpoint definition alone.

The endpoint definition itself presents an additional statistical issue. The stated bounds for the neutral category cannot both apply to a single SDLP difference, and the registry does not clarify the intended rule. A category boundary must be unambiguous for counts to be reproducible and interpretable. The wording should therefore be treated as a documentation limitation rather than silently corrected.

Finally, the safety record illustrates why counts need context. It records no serious adverse experiences in the listed conditions, but these counts do not provide a complete description of uncertainty or establish absence of risk. Overall, this trial record is useful for understanding how the question was framed and what outcomes were planned, while the missing outcome estimates and analysis details sharply limit statistical interpretation.

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 for interpreting efficacy is that the primary endpoint category counts are not reported in the registry record. Numerical results for the listed secondary driving outcomes are also not reported. Without these results, there is no basis in the recorded information for describing the observed treatment differences, their direction, or their precision.

The primary endpoint's neutral-category definition is internally inconsistent: it gives a lower bound of at least 2.5 cm and an upper bound of at most -2.5 cm. The record does not clarify the intended rule. This creates uncertainty about how that category should be understood and whether its definition was transcribed correctly.

The registry identifies a four-way crossover design but does not report the treatment sequence, interval between periods, handling of period or carryover effects, or statistical model. Participant flow, endpoint-specific analysis counts, and missing-data handling are not reported in the registry record. These omissions prevent a full assessment of whether the analysis reflected the repeated-measures structure and how missing observations may have affected comparisons.

The record lists 9 outcome measures and 15 analyses, but the multiplicity strategy and detailed statistical plan are not reported. It also does not report a sample-size justification for the trial. The healthy adult volunteer population limits direct generalization beyond the population described. Finally, the adverse-event listing gives serious-event counts and non-serious counts, but the listed safety information does not include event terms or death counts. These are limitations of the registry record, not evidence that unreported methods or outcomes had a particular result.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet — NCT01106859.
• Registry record last updated 2012-02-14; status last verified 2012-02.
• Results first posted 2012-01-20.
• 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.

18. Record Summary

NCT01106859 is a completed Phase 1, single-center, randomized, triple-masked, placebo-controlled, four-way crossover study sponsored by Transcept Pharmaceuticals. The official title calls the study double-blind. It enrolled 40 healthy adult volunteers and assessed next-morning highway-driving performance after zolpidem tartrate sublingual tablet 3.5 mg administered in the middle of the night.

The four conditions were zolpidem 3 hours before driving, zolpidem 4 hours before driving, zopiclone at bedtime 9 hours before driving, and placebo. The primary endpoint counted participants classified as worse, neutral, or improved relative to placebo using a 2.5 cm SDLP threshold, with an assessment timeframe of 3-9 hours post dose. The registry record does not report the primary category results, and its neutral-category definition is internally inconsistent.

The safety record reports 0 serious adverse experiences in each condition. The primary outcome population is listed as intent to treat. Detailed analysis methods, multiplicity procedures, and missing-data handling are not reported in the registry record.