A Study of the Safety and Effectiveness of ADX-N05 for Excessive Daytime Sleepiness in Subjects With Narcolepsy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Safety and Effectiveness of ADX-N05 for Excessive Daytime Sleepiness in Subjects With Narcolepsy (NCT01681121), a randomized phase 2 study. The primary outcome is Change From Baseline in the Average Sleep Latency Time (in Minutes) as Determined From the Maintenance of Wakefulness Test (MWT) for ADX-N05 300 mg vs. Placebo at Last Assessment..

2. Clinical Question

The registry record describes a Phase 2 study of ADX-N05 for excessive daytime sleepiness in people with narcolepsy. The clinical question is focused on a measurable ability to stay awake, rather than on a diagnosis or a long-term health outcome. The Maintenance of Wakefulness Test (MWT) records sleep latency during set opportunities to remain awake; the outcome uses the average from the first four trials.

The primary endpoint covers change from baseline to Week 12 or the last available post-baseline assessment. This comparison therefore concerns the difference between groups in average change over the stated assessment period. It is not a comparison of final scores alone. Baseline values, individual participant trajectories, and detailed assessment schedules are not reported in the registry record.

The registry also lists patient- and clinician-rated measures and additional MWT outcomes. Those measures can address related aspects of sleepiness and perceived change, but they are not interchangeable with the objective primary measure. The available record does not set out a clinical threshold for a meaningful MWT or questionnaire change, nor does it identify a primary analysis population in the population field. The result should consequently be read as a comparison of the posted group summaries, not as a complete account of which participants were eligible for each analysis or how each individual’s change was classified.

3. Trial Design

This was a randomized, parallel-group, placebo-controlled, multicenter Phase 2 study. The registry lists triple masking. It does not identify which groups of people were masked, so the masking label alone cannot establish the exact procedures used to maintain masking. Enrollment was 93. The record describes the study as completed, with a start date of 2012-09 and primary completion in 2013-08.

The intervention and comparator descriptions state that ADX-N05 and matching placebo were taken once a day for 12 weeks. The primary outcome title specifies ADX-N05 300 mg, while a secondary MWT outcome specifies ADX-N05 150 mg. The record does not provide a fuller account of dose assignment, dose changes, adherence, or whether other doses were used in other outcomes. The primary outcome timeframe is baseline up to Week 12 or the last assessment after dosing.

The primary endpoint was the change from baseline in average sleep latency across the first four MWT trials. The outcome description says the MWT is a validated objective measure of the ability to stay awake for a defined period. The stated primary analysis compared treatment and control group changes using a two-sample t-test. Other analysis details—including adjustment variables, analysis population, and handling of missing endpoint values—are not reported in the registry record.

The registry lists 10 outcome measures and eight secondary outcomes. The detailed posted secondary comparisons include an MWT average at Week 4 and Epworth Sleepiness Scale (ESS) changes at Week 4 and the last assessment. Other listed secondary outcomes include individual MWT trials and participant or clinician global-impression outcomes. Numerical results for those other listed outcomes are not reported in the registry record. The record lists no reported analyses, so it does not give a fuller statistical analysis plan or an account of how the secondary outcomes were analyzed.

Although total enrollment is recorded as 93, the primary outcome summaries use 40 participants in the ADX-N05 group and 45 in the placebo group. These are the group counts attached to the posted outcome summaries, not an explanation of participant flow. Reasons why those counts differ from enrollment, how many participants were randomized or treated, and how missing observations affected each analysis are not reported in the registry record. No assumptions about those points can be recovered from the posted group means and standard deviations.

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

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 Change From Baseline in the Average Sleep Latency Time (in Minutes) as Determined From the Maintenance of Wakefulness Test (MWT) for ADX-N05 300 mg vs. Placebo at Last Assessment., measured over Baseline up to Week 12/Last Assessment post-dose..

The primary endpoint is change from baseline in average sleep latency, measured in minutes with the Maintenance of Wakefulness Test. The outcome averages the first four MWT trials and compares ADX-N05 300 mg with placebo at the last assessment. The timeframe is baseline up to Week 12 or the last post-dose assessment. A positive change indicates an increase in the recorded time before sleep during the test, while the endpoint description frames the test as an objective measure of the ability to stay awake for a defined period.

Using change from baseline focuses the comparison on how the measured outcome shifted during follow-up, rather than only on the values at the end of follow-up. Averaging several trials is the outcome definition stated in the registry; it represents repeated test observations in one summary measure. These features do not, by themselves, explain how missing trials were handled or whether all participants completed every trial. Those procedures are not reported in the registry record.

An objective test can complement reports of how sleepy a participant feels, but it measures a different aspect of the experience. The registry includes ESS and global-impression outcomes among the secondary measures. It does not provide a clinical threshold for a meaningful change in the MWT, or explain how a change in minutes should be translated into day-to-day function. The primary endpoint therefore gives a quantified test result, not a complete account of symptoms, functioning, or longer-term outcomes.

7. Results Posted in the Registry

• ADX-N05: mean 12.80 versus 2.10 on control; difference 10.70 (95% CI 6.77 to 14.63), standardized effect d = 1.18; z-test p = <0.001.

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.

Change From Baseline in the Average Sleep Latency Time (in Minutes) as Determined From the Maintenance of Wakefulness Test (MWT) (Average of the First Four Trials) Following Four Weeks of Treatment With ADX-N05 150 mg vs. Placebo

• 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:
  • ADX-N05: mean 9.50 versus 1.40 on control; difference 8.10 (95% CI 4.69 to 11.51), standardized effect d = 1.02; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for ADX-N05 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in Epworth Sleepiness Scale (ESS) Scores for ADX-N05 vs. Placebo at Week 4

• 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:
  • ADX-N05: mean -5.60 versus -2.40 on control; difference -3.20 (95% CI -5.32 to -1.08), standardized effect d = -0.65; z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for ADX-N05 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in ESS Scores for ADX-N05 vs. Placebo at Last Assessment

• 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:
  • ADX-N05: mean -8.50 versus -2.50 on control; difference -6.00 (95% CI -8.26 to -3.74), standardized effect d = -1.10; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for ADX-N05 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary continuous outcomes show a generally aligned numerical pattern across two related kinds of measurement: MWT sleep latency and ESS score change. The ADX-N05 group’s mean change is higher for the MWT average at Week 4, while its ESS changes are more negative at Week 4 and at the last assessment. This overall pattern is directionally consistent with the primary MWT comparison in the sense that the group summaries separate in the same broad direction for the outcomes as recorded.

That consistency should not be overstated. An MWT result and an ESS result do not measure exactly the same thing: one is an objective test of remaining awake, and the other is a questionnaire score. The record does not provide a threshold for meaningful change on either scale, detailed participant-level data, or an explanation of how the measures relate within participants. It also lists global-impression measures and individual MWT trials, but their numerical results are not reported in the registry record.

The registry lists eight secondary outcomes, but detailed numerical comparisons are posted for three. The record lists 10 outcome measures and zero reported analyses. This means the available secondary results do not give a complete numerical account of every listed outcome. It is not possible to tell from the registry record whether omitted numerical results were unavailable, not analyzed, or not posted.

Unadjusted secondary results carry less weight than a single prespecified primary comparison because examining multiple outcomes and assessment times increases the chance of seeing apparently notable results by chance. In general, multiplicity procedures can account for that concern, but the registry record does not report whether any such procedure was planned or used. The listed p-values are unadjusted. These secondary findings can provide supporting context for the primary result, but they should not be treated as independent proof or as replacements for the primary endpoint.

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

• Change From Baseline in the Average Sleep Latency Time (in Minutes) as Determined From the Maintenance of Wakefulness Test (MWT) (Average of the First Four Trials) Following Four Weeks of Treatment With ADX-N05 150 mg vs. Placebo
• Change From Baseline in Sleep Latency Time (in Minutes) as Determined From Each of the 5 Individual MWT Trials for ADX-N05 vs. Placebo at Week 4
• Change From Baseline in Sleep Latency Time (in Minutes) as Determined From Each of the 5 Individual MWT Trials for ADX-N05 vs. Placebo at Last Assessment
• Change From Baseline in Epworth Sleepiness Scale (ESS) Scores for ADX-N05 vs. Placebo at Week 4
• Change From Baseline in ESS Scores for ADX-N05 vs. Placebo at Last Assessment
• Number of Participants With Improved Clinical Global Impression of Change (CGI-C) Scores for ADX-N05 vs. Placebo at Week 4
• Number of Participants With Improved Patient Global Impression Change (PGI-C) Scores for ADX-N05 vs. Placebo at Week 4
• Number of Participants With Improved PGI-C Scores for ADX-N05 vs. Placebo at Last Assessment

9. Statistical Interpretation

10. Statistical Methods Explained

The registry describes the primary outcome as a continuous measure: change in MWT sleep latency, in minutes. For a continuous outcome, a group mean summarizes the average observed value, while a standard deviation describes how dispersed individual observations are around that mean. These are different quantities. A standard deviation is not an uncertainty interval for the group mean or for the treatment comparison.

What does the mean difference represent?

The comparison is defined as the ADX-N05 mean minus the placebo mean. For the primary endpoint, the group means are 12.8 and 2.1 minutes, respectively, and the posted mean difference is 10.7 minutes. The positive sign means the ADX-N05 group had a larger mean change in the recorded endpoint. It does not mean that each participant changed by that amount; it is a difference between group averages. The standard deviations, 10.28 and 7.88 minutes, indicate that individual changes varied around those averages.

The same general interpretation applies to the secondary continuous outcomes, although the meaning of a positive or negative value depends on the scale. MWT outcomes are measured in minutes. ESS outcomes are scores on a scale, and the posted differences are negative. The registry record does not give a clinically meaningful threshold for ESS change, so the statistical direction and magnitude should not be converted into a claim about a particular level of symptom improvement.

What does the two-sample t-test do?

The primary outcome description says the treatment groups were compared using a two-sample t-test on change from baseline. In general, a two-sample t-test evaluates whether the observed difference between two group means is compatible with a null hypothesis of no difference, while accounting for estimated variability and the number of observations. The p-value is calculated relative to that null model and its assumptions. It does not measure the chance that the null hypothesis is true, and it does not describe the probability that an individual participant will have a particular outcome.

The posted primary unadjusted p-value is <0.001. It is a small p-value under the comparison as calculated, but it should be read alongside the estimated difference and its interval. A p-value alone does not say whether a difference is important to patients or whether the statistical assumptions and missing-data decisions are appropriate. The registry identifies the test but does not report diagnostic checks, covariate adjustment, or detailed implementation choices.

Why consider variability and distribution?

A mean-and-standard-deviation summary is most directly informative when the mean is a useful description of the data and the inference is not unduly affected by extreme observations or strong departures from the model’s assumptions. The t-test is commonly used for comparing means; its performance depends on the data and design. The registry does not provide participant-level observations, plots of the endpoint distribution, or diagnostic analyses, so distributional shape and the influence of extreme changes cannot be assessed from the summary statistics alone.

General statistical note: over-dispersion means that the observed variability is greater than a model expects. When a model underestimates variability, its uncertainty estimates can be too narrow and its tests can be too optimistic. This concern is especially relevant to models for counts or clustered observations; it is not something that can be diagnosed from the primary endpoint’s two group standard deviations alone. No over-dispersion assessment is reported in the registry record.

How should the interval and p-value be read together?

An interval estimate gives a range of values compatible with the data and the calculation’s assumptions, rather than a single point estimate alone. For the primary difference, the posted interval extends from 6.769 to 14.63 minutes, while the estimated mean difference is 10.7 minutes. The interval indicates uncertainty around the estimated difference; it is not a range containing every participant’s response. The registry record does not state the interval’s confidence level, so no confidence percentage should be attached to it based on this information alone.

The interval and p-value answer related but distinct questions. The p-value summarizes how incompatible the observed data are with a specified null comparison under the statistical model. The interval shows a range of plausible magnitudes under its method. Neither accounts automatically for bias from selective reporting, deviations from the planned analysis, or missing data. The primary description specifies a t-test, but the registry record does not report all methods needed to evaluate those potential sources of uncertainty.

What does a standardized effect add?

A standardized effect expresses a mean difference relative to a measure of pooled variability. The posted primary standardized effect is 1.178. This can help describe the observed separation relative to the within-group spread, but it is not in minutes and does not replace the original-scale estimate. It is also not a clinical threshold. Standardized effects can be sensitive to the population’s variability and are not directly interpretable as a change in daily functioning.

The standardized effect is based on the posted summaries. It is not an independent confirmation of the result, because it uses the same group data as the mean difference. The original scale remains important for clinical interpretation, and the registry does not supply a threshold that would establish what magnitude matters to participants.

What information is unavailable?

The registry record does not report the analysis population, an account of participant flow by outcome, missing-data methods, covariate adjustments, or a full statistical analysis plan. The primary outcome description gives the test and the comparison period, but not these other details. The record also lists no reported analyses. That limits assessment of whether all planned outcomes and analysis decisions are represented in the posted results.

General statistical note: randomized allocation helps make groups comparable on average, but it does not remove the need to describe who was analyzed and how missing measurements were handled. If outcome availability differs between groups, a comparison among participants with observed measurements can differ from the comparison intended by the trial. The group summaries alone cannot establish whether such differences occurred. These limitations do not negate the numerical comparison; they bound what can be concluded from it.

11. Confidence Intervals and Precision

The primary mean difference is 10.7 minutes, and its posted interval runs from 6.769 to 14.63. This interval is more informative about precision than the point estimate alone because it indicates the range of values compatible with the calculation. Its positive endpoints indicate that the posted interval does not cross zero. The registry record does not state the interval’s confidence level, so it should not be labeled with a particular confidence percentage.

The standard deviations show noticeable variation in both groups: 10.28 minutes for ADX-N05 and 7.88 minutes for placebo. This participant-level variation is distinct from uncertainty in the estimated group difference. The sample counts attached to the primary outcome are 40 and 45. The interval calculation reflects the summaries and its statistical assumptions, but it cannot show how robust the result is to unreported choices about missing values or analysis population.

A narrower interval would indicate greater precision under the same inferential framework; a wider interval would indicate less precision. Precision is not the same as clinical importance. Even a relatively precise estimate needs a meaningful-outcome threshold and context before its practical significance can be judged. Neither is reported for the primary endpoint. Nor does the interval capture all possible uncertainty due to design or reporting limitations, including the absence of detailed participant flow and an account of missing-data handling.

The secondary comparisons also have interval estimates, but they should not be treated as independent confirmations of the primary result. They concern related outcomes and assessment times, and the record does not report a multiplicity adjustment. Their precision should be interpreted together with the fact that several outcomes were considered and that only some have detailed numerical comparisons posted.

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 sample-size planning figures are illustrative calculations based on the observed effect, not the trial’s original design assumptions. The figures for these continuous comparisons are participants per arm, not total events. The listed planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a hypothetical study to have an 80% chance of detecting the specified effect under those assumptions, if that effect is the true one and the statistical model is appropriate. The 90% column uses a higher target chance of detection, so it generally calls for more participants per arm than the 80% target. These are planning targets, not guarantees about what a future study will find.

The rows that plan for 100%, 75%, and 50% of the observed effect explore different assumed effect sizes. A smaller effect is harder to distinguish from random variation, so detecting it at the same power generally requires more participants. The planning figures illustrate that relationship; they do not establish the effect that a future trial should expect or the appropriate design for a new study. The calculations are not observed power: they do not measure the probability that this completed trial detected an effect, and they do not change the interpretation of its observed estimates.

These estimates also rely on simplifying assumptions. Equal allocation, the normal approximation, the selected significance level, and use of a fraction of the observed effect are planning choices for the illustration. The record does not report whether the original trial used these assumptions. They should therefore be understood as a separate planning exercise, not as a reconstruction of the trial’s protocol or sample-size justification.

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 = 10.700; pooled standard deviation σ = 9.087.
2. n = 2 × (1.96 + 0.842)² × 9.087² / 10.700² = 11.3, rounded up to 12 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 <- 10.7                      # observed difference in means
sigma <- 9.08700329677846                     # 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(1681121)
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 = 12 (80% power), 16 (90% power)
 75% of observed effect: n per arm = 21 (80% power), 27 (90% power)
 50% of observed effect: n per arm = 46 (80% power), 61 (90% power)
power.t.test: 12.4 
Simulated power at n = 12 per arm: 0.783 (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 record includes a primary outcome and multiple secondary outcomes. It lists 10 outcome measures, including eight secondary outcomes, and detailed numerical comparisons are posted for three secondary outcomes. The registry record reports zero analyses. The primary outcome description names a two-sample t-test, but it does not describe a plan for controlling the chance of false-positive findings across outcomes, assessment times, or comparisons.

Multiplicity is the statistical issue that arises when several hypotheses are examined. In general, testing more outcomes creates more opportunities for a small p-value to occur by chance, even when no true difference exists for any one outcome. Adjusting for multiplicity can make inference more conservative or can organize which comparisons are confirmatory. The registry record does not report whether an adjustment, hierarchy, or other strategy was planned or applied. The secondary p-values are therefore unadjusted and should be regarded as exploratory context rather than definitive confirmation.

Missing-data information is also limited. Primary outcome counts are 40 for ADX-N05 and 45 for placebo, while enrollment is 93. The registry does not explain the relationship between enrollment and the group counts used in the outcome summaries. It does not report participant flow, reasons for unavailable outcomes, the number with baseline and follow-up measurements, or a method for handling missing values. No inference about why the counts differ is warranted from the available summaries.

The population analyzed for the primary endpoint is not identified in its population field. The registry record does not state whether the comparison used all randomized participants, participants who received treatment, or another analysis population. The analysis population for the secondary outcomes is likewise not specified. This matters because the population included and the treatment of missing measurements can affect the interpretation of a group comparison.

The primary endpoint description provides a test and an assessment period, but other elements of the statistical plan—including covariate adjustment, assumptions about missing data, and multiplicity procedures—are not reported in the registry record. These gaps limit the ability to assess whether the posted summaries represent the full intended analysis. They do not change the stated group means, but they make the uncertainty around broader claims greater than the interval estimate alone conveys.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: conversion disorder (2.3%), cholecystitis acute (2.3%).

The serious adverse event summaries give the number at risk and the number affected in each group. For ADX-N05, 44 participants were at risk and 2 had a serious adverse event; for placebo, 49 were at risk and 0 had a serious adverse event. The listed serious-event terms are Conversion Disorder and Cholecystitis Acute, each reported at 2.3%. The record reports zero deaths in each group.

These figures describe events recorded in this trial; they do not establish that a treatment caused an event or that the groups have different underlying risks. The summaries do not provide event timing, duration, severity beyond the serious-event classification, relatedness assessments, or a fuller account of how events were collected. Those details are not reported in the registry record.

The record also lists other adverse events affecting 21 participants at risk in the ADX-N05 group and 12 in the placebo group, with 44 and 49 at risk, respectively. These are separate from the serious adverse event counts. The registry summary does not provide additional context in the figures to determine event type, duration, or clinical importance. Group-level counts should therefore be read as descriptive safety information, not as a complete safety assessment.

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

The posted primary result is a comparison of average changes in an objective measure of wakefulness during an assessment period. The ADX-N05 group’s mean change was 12.8 minutes and the placebo group’s was 2.1 minutes; the mean difference was 10.7 minutes, with an interval from 6.769 to 14.63 and an unadjusted p-value of <0.001. This describes the observed group summaries for the primary endpoint. It does not establish how every participant responded, or what the result means for a person outside this trial.

The result is specific to the MWT average across the first four trials and the last assessment, up to Week 12 or the last available post-baseline assessment. It does not by itself establish longer-term effects, effects on daily functioning, or outcomes not measured in the record. The study is described as Phase 2, and the registry record does not report follow-up beyond the stated treatment and assessment timeframe.

Statistical evidence and clinical importance are related but distinct. The small unadjusted p-value and interval estimate describe the comparison under the statistical calculation; they do not define a threshold for a meaningful change. No threshold for interpreting the MWT difference is reported. The secondary ESS results are on a different scale, and the registry record does not state a meaningful-change threshold for that measure either.

The record also does not report enough information to judge all aspects of analysis conduct. The primary outcome population field is blank, participant flow is not described in detail, and missing-data handling and multiplicity procedures are not reported. These limitations restrict how confidently the result can be generalized or treated as a complete account of all outcomes. The summaries can be described as showing a group difference in the posted primary measure, without turning that finding into medical advice or a claim about an individual’s likely experience.

The safety figures provide a limited account of serious and other adverse events during the study. The presence or absence of recorded events in these group summaries cannot settle questions about causation or rare risks. Further details about event collection and follow-up are not reported in the registry record. The posted efficacy and safety results should therefore be understood within the specific study design, measured outcomes, and available reporting.

17. Why This Trial Matters Statistically

This trial is statistically informative because it sets out a randomized, placebo-controlled comparison and defines an objective primary measure before presenting group summaries. The primary outcome is based on a continuous measure, so the mean difference retains the original unit of minutes. That makes the estimate easier to relate to the test itself than a standardized effect alone, while the interval indicates uncertainty around the estimated group contrast.

The record also illustrates why statistical interpretation needs more than a p-value. The primary mean difference, interval, group standard deviations, and unadjusted p-value each describe a different feature of the evidence: estimated magnitude, uncertainty, within-group variation, and compatibility with a null comparison under the test assumptions. Taken together, they offer a more complete description of the posted primary result than a significance label alone.

The secondary outcomes add useful context because they include both an objective test and a symptom questionnaire. Their broad numerical direction is similar to the primary result, but the registry lists several outcomes and does not report a multiplicity strategy. This highlights the distinction between a coherent pattern across measures and formal evidence that accounts for the number of comparisons. The record also shows how missing population and data-handling details constrain the interpretation of otherwise clear summary statistics.

Finally, the planning illustrations demonstrate how assumed effect size and target power influence sample-size planning. They are based on the observed effect and stated planning assumptions, not on the original design justification. Separating such planning calculations from the completed trial’s observed results is essential: a hypothetical design calculation cannot establish what the trial was planned to detect or how likely it was to detect its observed effect.

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.

The most important trial-specific limitation in interpreting the posted results is the incomplete account of participant flow and outcome availability. Enrollment is 93, whereas the primary outcome summaries have group counts of 40 and 45. The record does not explain this difference, identify the primary analysis population, or state how missing measurements were handled. It is therefore not possible to determine from the posted summaries alone how representative the analyzed observations are of all enrolled participants.

The registry lists multiple secondary outcomes but gives numerical comparisons for only three. Other listed measures include individual MWT trials and improved clinical or patient global-impression scores. Their numerical results are not reported in the registry record. Because the record lists zero reported analyses, it also does not give a full account of which analyses were performed or how the available results relate to all listed outcomes. The risk of selective outcome reporting cannot be evaluated from these summaries alone.

The primary analysis description specifies a two-sample t-test, but the record does not report model checks, covariate adjustment, or the detailed statistical analysis plan. The population field for the primary endpoint is blank. The record also does not report a multiplicity strategy, despite the number of listed outcomes. These gaps affect how fully the posted p-values and interval estimates can be assessed.

The clinical interpretation is limited by the absence of meaningful-change thresholds for the MWT and ESS, as well as the absence of detailed participant characteristics and eligibility criteria. The record describes a population of adults with narcolepsy, but does not provide further information to judge how broadly the results apply. Follow-up beyond the stated 12-week treatment period is not reported. Safety summaries also lack event timing, relatedness, and other contextual details. These limits call for conclusions that stay specific to the reported outcomes and timeframe.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study of the Safety and Effectiveness of ADX-N05 for Excessive Daytime Sleepiness in Subjects With Narcolepsy — NCT01681121.
• Registry record last updated 2021-05-28; status last verified 2021-05.
• Results first posted 2014-09-11.
• 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

The registry describes a completed, randomized, triple-masked, parallel-group, multicenter Phase 2 study of ADX-N05 versus matching placebo for excessive daytime sleepiness in adults with narcolepsy. Enrollment was 93. The study start date was 2012-09, and primary completion was 2013-08. Both intervention descriptions state once-daily treatment for 12 weeks.

The primary outcome was change from baseline in average sleep latency across the first four MWT trials at the last assessment. The posted group means were 12.8 minutes for ADX-N05 and 2.1 minutes for placebo; the mean difference was 10.7 minutes, with an interval from 6.769 to 14.63 and an unadjusted p-value of <0.001. The registry also lists secondary outcomes and adverse-event summaries, while analysis-population, missing-data, multiplicity, and several outcome details are not reported in the registry record.