Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy (NCT00232141), a randomized phase 3 study. The primary outcome is Change From Baseline for Numerical Rating Scale (NRS) Pain Scores at Endpoint-LOCF (Last Observation Carried Forward) Relative to Baseline.

2. Clinical Question

3. Trial Design

The registry identifies NCT00232141 as a completed phase 3 study of pregabalin versus placebo for neuropathic pain associated with HIV neuropathy. It describes randomized allocation, quadruple masking, and a parallel-group model. The official title also identifies the study as double-blind, placebo-controlled, and multicenter. Enrollment was 302. The listed start was 2005-10 and primary completion was 2007-11.

The interventions were pregabalin and placebo. The registry does not give dose, titration schedule, treatment duration details beyond the Week 14 primary timeframe, or further arm-specific procedures. Those details are not reported in the registry record. The primary endpoint is a continuous pain score, with the registry reporting least-squares means and standard errors for change from baseline. The primary comparison is also reported as an ANCOVA mean difference in final values.

The primary analysis population is described as the ITT population, or full analysis set: randomized participants who took at least one dose and had at least one post-randomization efficacy assessment. The registry also states that the endpoint-LOCF mean value was computed from the last 7 diary entries, from Day 2 up to and including the day after the last dose within the dose-adjustment or main period. The text of that population description is incomplete in the registry record, so further detail is not reported there.

The study lists 33 outcome measures and 156 analyses, including secondary measures of sleep, anxiety and depression, pain interference, patient global impression, neuropathic pain symptoms, and quantitative assessment of neuropathic pain. The registry does not describe the original sample-size justification, interim analyses, or a complete prespecified statistical plan; these 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.

Before assignment: A total of 472 subjects were screened for the study, and 302 subjects were randomized to study treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT population (ie, full analysis set)=all randomized participants who took at least 1 dose \& had at least 1 post-randomization efficacy assessment. The endpoint-LOCF mean value was computed from last 7 diary entries (Day 2 up to and including the day after the last dose w/n Dose-Adjustment or Maintenance phase (up to Day 99).

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 for Numerical Rating Scale (NRS) Pain Scores at Endpoint-LOCF (Last Observation Carried Forward) Relative to Baseline, measured over Baseline, Week 14.

The primary endpoint is change from baseline in mean Numerical Rating Scale pain scores at endpoint-LOCF, with baseline and Week 14 identified as the timeframe. Participants recorded daily pain on an 11-point scale, from 0 for no pain to 10 for worst possible pain. A change score expresses how the recorded pain score at follow-up differs from the participant’s baseline score. The registry reports group least-squares means and standard errors for this continuous measure.

Using repeated diary entries can represent pain over a period rather than relying on one isolated rating. The endpoint-LOCF approach uses the last available diary observations as described in the record, rather than requiring a complete final diary for every participant. This choice also means that the endpoint value may draw on observations from different points in follow-up when participants have different last recorded entries. The precise implications depend on the missing-data pattern and the analysis assumptions, which are not fully described in the registry record.

A between-group comparison is needed to assess whether average change differed between randomized groups. Within-group improvement alone cannot distinguish a treatment-related difference from changes that may occur in both groups. The endpoint is therefore useful as a measure of reported pain change, but it does not by itself describe every dimension of neuropathic pain or patient experience.

7. Results Posted in the Registry

• Pregabalin: mean -2.88 versus -2.63 on control; difference -0.25 (95% CI -0.83 to 0.33), standardized effect d = -0.10; z-test p = 0.400.

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 for NRS-Sleep Interference Scores

• 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 errors.
• Result:
  • Pregabalin: mean -2.53 versus -2.34 on control; difference -0.19 (95% CI -0.74 to 0.36), standardized effect d = -0.08; z-test p = 0.502.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pregabalin and the control. The interval gives the range of effects that remain compatible with the data.

Gracely Pain Scale Score

• 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:
  • Pregabalin: mean -2.70 versus -2.76 on control; difference 0.06 (95% CI -0.74 to 0.86), standardized effect d = 0.02; z-test p = 0.884.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pregabalin and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover several related but distinct aspects of pain and wellbeing: sleep, sleep interference, anxiety and depression, pain inventory scores, patient global impression, neuropathic pain symptoms, and quantitative assessment of neuropathic pain. This breadth can help describe whether the primary pain score is accompanied by changes in other measured domains. It also means that the secondary outcomes do not all answer the same question or use the same scale.

The posted secondary results do not provide a consistent basis for overturning or strengthening the primary interpretation. The available detailed comparisons include estimates near zero relative to their uncertainty, and their intervals include no difference. These outcomes should be read as complementary descriptions, not as independent confirmations of a treatment effect. A secondary measure can capture a meaningful dimension that the primary endpoint does not, but its result does not replace the registered primary comparison.

The registry lists 33 outcome measures and 156 analyses, while 28 secondary outcomes are posted. When many outcomes or analyses are examined, some apparently notable findings can arise by chance even when there is no underlying group difference. Unadjusted secondary p-values do not account for the full set of comparisons and therefore carry less weight than a result supported by a prespecified primary analysis. The record does not report a multiplicity adjustment strategy, so it is not possible to determine whether or how the sponsor controlled the chance of false-positive findings across secondary analyses.

Accordingly, the secondary outcomes are most useful for contextualizing the primary result and identifying domains for further study. Their interpretation should remain cautious, especially where the registry provides summary statistics but no sponsor-reported inferential analysis. The available record does not establish a coherent pattern of secondary findings that changes the central uncertainty in the primary outcome.

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

• Change From Baseline for MOS (Medical Outcomes Study)-Sleep Subscales and Sleep Problem Indices
• Change From Baseline for Hospital Anxiety and Depression Scale (HADS) Subscales
• Change From Baseline for Modified Brief Pain Inventory-Short Form (mBPI-sf) Scores
• Change From Baseline for NRS-Sleep Interference Scores
• Categorized Patient Global Impression of Change (PGIC)
• Patient Global Impression of Change (PGIC) Rating
• Change in Neuropathic Pain Symptom Inventory (NPSI) Subscores and Total Intensity Scores
• Change in Quantitative Assessment of Neuropathic Pain (QANeP)

9. Statistical Interpretation

10. Statistical Methods Explained

What does a change score represent?

A change score compares a follow-up measurement with a baseline measurement. Here, the outcome is a numerical rating of pain, and the registry reports mean changes for pregabalin and placebo. Because lower scores correspond to less pain on the described scale, a negative change represents a decrease from baseline. To answer the comparative question, the focus is the difference between the group changes, not whether one group’s change is individually different from zero.

Group averages give a compact description, but they do not show the full spread of individual responses. A mean can conceal substantial variation: some participants may have larger changes, others smaller changes, and some may move in the opposite direction. The registry’s primary outcome reports standard errors for the least-squares means, rather than standard deviations. A standard error describes uncertainty in an estimated mean, not the spread of individual participant scores.

What is a least-squares mean?

A least-squares mean is an adjusted group mean estimated within a statistical model. It can differ from a simple arithmetic average because it reflects the model’s specification and any included covariates. The registry labels the primary outcome values as least-squares means and identifies ANCOVA as the sponsor’s method for the between-group comparison. However, the registry record does not identify the ANCOVA covariates or provide the full model specification. Those details are not reported in the registry record.

ANCOVA, or analysis of covariance, compares groups while accounting for one or more measured variables in a model. In a trial, baseline outcome values may be included to improve estimation of a follow-up group contrast. That is a general explanation of the method, not a statement about the exact covariates used in this trial. Because the model details are absent, the reported ANCOVA result cannot be independently reconstructed in full from the record.

How should the reported and recalculated comparisons be distinguished?

The registry’s own analysis is an ANCOVA comparison reported as a mean difference in final values. The accompanying recalculation is an unadjusted comparison derived from posted summary statistics. It is useful as a transparent check on the scale and broad direction of the result, but it is not the same analysis as the sponsor’s model. The sponsor’s estimate and interval should be treated as the trial’s own inferential result; the recalculation does not recover adjustments or modeling choices that are not reported.

The recalculated interval describes plausible values for the group contrast under the assumptions used for that simple calculation. It is not a substitute for the interval from the trial’s model. The posted estimates are close, and the inferential reading is similar: the estimated contrast is modest and uncertainty includes no difference. Since the registry marks no discrepancy, there is no material conflict between the reported and recalculated estimates in the posted summaries.

What does a p-value say?

A p-value 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, and it does not measure the size or importance of an effect. The primary sponsor-reported p-value is 0.391, while the simple unadjusted recalculation gives p = 0.4. Both are above the conventional 0.05 threshold used in the planning illustration and do not constitute evidence of a statistically significant between-group difference under that threshold.

Failure to cross a significance threshold does not establish that the true effect is exactly zero. The effect estimate and confidence interval carry information about possible magnitude and direction, while the p-value gives a test-based summary. Interpretation should consider all of these together rather than treating a single threshold as a complete verdict.

Why can over-dispersion matter?

Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. In continuous outcomes, greater variability makes group comparisons less precise and can widen uncertainty intervals. The posted primary outcome gives standard errors, but does not report a specific over-dispersion assessment or model diagnostic. No claim about over-dispersion in this trial can therefore be made. The general point is that precision depends not only on group size but also on the variability and structure of the measurements.

Diary outcomes can also be correlated within a participant: adjacent daily scores from one person are generally not independent observations in the way measurements from different people might be. A statistical method that analyzes repeated diary data would need to account for that dependence. The registry’s endpoint description says that the endpoint-LOCF mean was computed from the last 7 diary entries, but does not give enough information to determine how the underlying diary observations were modeled. That modeling detail is not reported in the registry record.

11. Confidence Intervals and Precision

The primary sponsor-reported estimate is a mean difference of -0.25, with a 95% confidence interval from -0.83 to 0.32. A confidence interval is a range of values that reflects sampling uncertainty under the statistical model and its assumptions. It is not a guarantee that the true effect lies within the particular interval, nor does it assign a probability to the effect after the data have been observed.

Because this interval includes zero, the posted analysis is compatible with no average difference between groups. It also includes values favoring either group. The interval’s span indicates that the estimate is not precise enough to pin down a single narrow effect size. The point estimate is more favorable to pregabalin, but the uncertainty around it should remain central to interpretation.

The registry reports an ANCOVA interval, while the recalculation is based on posted summary statistics and uses a different, unadjusted approach. The recalculated interval and the registry interval are not identical; the registry’s analysis is the trial’s own inferential result. Both lead to the same broad reading that the interval includes zero. The record does not report a threshold for clinical importance, so the interval cannot be judged against a registry-defined clinically meaningful margin.

Precision is affected by the number of analyzed participants, outcome variability, and the analysis model. The outcome-specific group sizes are not identical across all measures, and the registry’s primary population definition requires both a dose and a post-randomization efficacy assessment. The record does not report enough detail about missing observations or model covariates to determine their contribution to precision. Thus, the interval is informative but should be read in the context of the endpoint-LOCF approach and incomplete reporting of analysis details.

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 figures are planning illustrations based on the observed effect, not the trial’s original design calculation. For these continuous outcomes, the figures are participants per arm, not a combined total. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers detecting a stated fraction of the observed effect.

The 80% power column describes the number of participants per arm that the planning calculation estimates would be needed for an 80% chance of detecting the chosen effect at the stated significance level, if the planning assumptions hold. The 90% power column describes the corresponding planning number for a 90% chance. Higher planned power requires more participants, all else equal. The values are not observed power.

The rows for 100%, 75%, and 50% of the observed effect illustrate how the calculation changes when the target effect is smaller than the observed estimate. Smaller effects are harder to distinguish from random variation and therefore require more participants per arm under the same assumptions. These values should be read as conditional planning scenarios, not as a claim that any particular future study would attain the assumed effect or variability.

The trial’s own original sample-size assumptions and justification are not reported in the registry record. The listed planning inputs should not be mistaken for the protocol’s design assumptions. The figures also do not account for details that are not specified in the illustration, such as any adjustment for missing outcomes or multiple comparisons.

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 = -0.250; pooled standard deviation σ = 2.489.
2. n = 2 × (1.96 + 0.842)² × 2.489² / -0.250² = 1,556.2, rounded up to 1,557 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 <- -0.25                      # observed difference in means
sigma <- 2.48920248920373                     # 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(232141)
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 = 1,557 (80% power), 2,084 (90% power)
 75% of observed effect: n per arm = 2,767 (80% power), 3,704 (90% power)
 50% of observed effect: n per arm = 6,225 (80% power), 8,334 (90% power)
power.t.test: 1557.2 
Simulated power at n = 1,557 per arm: 0.801 (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. Analyses Reported by the Sponsor

The registry’s own primary analysis is an ANCOVA mean difference of -0.25, with a 95% confidence interval from -0.83 to 0.32 and p = 0.391. This is the trial’s reported analysis and is the appropriate result to prioritize when describing the sponsor’s inferential finding. The estimate is close to the simple recalculation from the posted group summaries, which gives a mean difference of -0.25 and p = 0.4.

The recalculation is unadjusted and uses summary statistics; it does not reproduce the ANCOVA model. The registry does not report the covariates or full modeling details needed to reconstruct that analysis. Therefore, a difference in the last decimal places or in interval endpoints should not be interpreted as a contradiction between methods. The record indicates no discrepancy, and the two approaches support the same broad interpretation: the estimated difference is small relative to its uncertainty, and the sponsor analysis does not show a statistically significant difference at the conventional threshold.

The registry also reports ANCOVA results for the NRS sleep-interference outcome, but not for the posted Gracely Pain Scale result. This difference in reporting means the available secondary analyses do not all have the same inferential detail. No unreported sponsor model or analysis should be inferred from the posted summaries.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several hypotheses are tested. With more outcomes, time points, subgroups, or analytic choices, the chance of at least one apparently unusual result can increase. The registry lists 33 outcome measures and 156 analyses, and 28 secondary outcomes are posted. These figures indicate a broad set of analyses, but do not reveal which analyses were prespecified, how they were organized into families, or whether any adjustment was applied.

The registry record does not report a multiplicity strategy. It is therefore not possible to say whether the sponsor adjusted secondary p-values, controlled a family-wise error rate, used a hierarchical testing plan, or designated some outcomes as exploratory. This missing information matters because nominal p-values for multiple secondary comparisons should not all be interpreted as if they were the sole confirmatory test. The primary analysis remains the clearest registered comparison for the main question.

Missing-data handling is partly described: the primary endpoint uses endpoint-LOCF based on the last 7 diary entries, and the stated ITT population includes randomized participants who took at least one dose and had at least one post-randomization efficacy assessment. These criteria mean the analysis population is not simply every randomized participant. The record does not report how many observations were missing, why they were missing, or whether missingness differed between groups. It also does not report sensitivity analyses using alternative assumptions about missing data.

LOCF carries an assumption that the last recorded value can stand in for a later unobserved value. In general, that assumption may not reflect a participant’s subsequent outcome, particularly if the outcome changes over time. This is a methodological concern, not evidence that the assumption caused bias in this trial. The registry record does not provide enough information to evaluate the direction or size of any such effect.

The exact analysis population and detailed model specification are also incompletely documented in the available record. The listed population definition is truncated, and ANCOVA covariates are not identified. These omissions limit independent assessment of missing-data handling, model adequacy, and the relationship between the analysis population and all randomized participants.

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

The posted primary result describes the average change in daily pain ratings for participants in the registry-defined analysis population, using an endpoint-LOCF measure. The estimated between-group difference is -0.25, and the sponsor-reported 95% confidence interval includes zero. The statistical evidence does not establish a clear difference between pregabalin and placebo for this primary outcome under the reported analysis.

This does not show that the true difference is exactly zero. The confidence interval allows effects in either direction, and the record does not define a clinical-importance threshold with which to judge the range. Nor does a nonsignificant result establish equivalence or noninferiority: the registry record does not identify an equivalence or noninferiority question or margin. The result should not be recast as a finding that the interventions are interchangeable.

The result also does not describe every participant’s experience. Group means cannot indicate how many individuals improved, remained unchanged, or worsened, and the posted primary summary does not provide responder proportions. The study’s secondary outcomes concern additional domains, but they do not change what the primary pain-score analysis directly estimates.

Interpretation is limited to the studied population, endpoint definition, timeframe, and analysis. The record identifies people with HIV infection and peripheral neuropathy, a baseline-to-Week 14 timeframe, and endpoint-LOCF. It does not report enough information to extend the result to other populations, durations, doses, or clinical settings. No medical recommendation follows from these registry summaries.

In statistical terms, the main message is uncertainty around an estimated group difference that is close to zero. The sponsor’s ANCOVA and the simple recalculation point to the same broad conclusion, while the available information leaves unresolved questions about missing data, model specification, multiplicity, and clinical importance.

17. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the distinction between change within groups and a randomized between-group contrast. The mean pain scores declined in both groups, but the trial’s primary question concerns whether their changes differed. A description of improvement in one arm alone would not answer that comparative question.

It also illustrates why an estimate should be read alongside its confidence interval. The estimated difference favors pregabalin under the reported direction convention, but the interval includes zero and spans effects in either direction. The p-value alone would omit the scale of the estimate and the range of values compatible with the analysis.

The trial combines a repeated diary-based measure with endpoint-LOCF, a named analysis population, least-squares means, and ANCOVA. Each choice shapes what is being estimated and how uncertainty is expressed. The registry reports some of these elements but not the full model, missing-data pattern, or sensitivity analyses. That makes this a useful example of how a result can be numerically interpretable while still leaving important methodological questions open.

Finally, the large set of listed outcomes and analyses provides a practical reminder that secondary findings need context. A wide outcome set can describe multiple dimensions of experience, but isolated unadjusted results should not be given the same confirmatory weight as the primary comparison. The record supports a careful reading of the primary result and restraint about claims beyond it.

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 registry record does not provide the trial’s dose or titration details, full eligibility criteria, or arm-specific descriptions. It identifies a Week 14 endpoint but does not provide further treatment-period detail in the available record. These omissions constrain interpretation of the treatment contrast and the population to which the result might apply.

The primary endpoint uses endpoint-LOCF, but the number and pattern of missing diary observations are not reported. The record also does not provide sensitivity analyses under alternative missing-data assumptions. As a result, the robustness of the estimate to missing-data handling cannot be assessed from the posted information.

The ANCOVA model is identified, but its covariates and full specification are not reported. The primary population description is truncated after the definition of participants who took at least one dose and had at least one post-randomization efficacy assessment. This prevents a full independent reconstruction of the sponsor’s analysis and limits assessment of how the analysis population relates to all randomized participants.

The registry lists many outcomes and analyses but does not report a multiplicity plan. The available secondary summaries are therefore difficult to interpret as confirmatory evidence, particularly where a sponsor-reported inferential analysis is absent. A clinical-importance threshold for the primary scale is also not reported, so statistical uncertainty cannot be translated into a registry-defined judgment of clinical relevance.

Finally, the posted aggregate summaries do not show participant-level distributions or response patterns. They cannot describe individual variation or identify whether effects differed across subgroups. Such subgroup findings, if any, are not reported in the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy — NCT00232141.
• Registry record last updated 2021-02-09; status last verified 2009-06.
• Results first posted 2009-08-11.
• 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

NCT00232141 is a completed phase 3 randomized, quadruple-masked, parallel-group, multicenter trial of pregabalin versus placebo for neuropathic pain associated with HIV neuropathy. Enrollment was 302; the listed start was 2005-10 and primary completion was 2007-11.

The primary endpoint was change from baseline in NRS pain scores at endpoint-LOCF, with a baseline-to-Week 14 timeframe. The sponsor-reported ANCOVA mean difference was -0.25, with a 95% confidence interval from -0.83 to 0.32 and p = 0.391. The interval includes zero, and the record does not establish a clear between-group difference on this endpoint.

The registry lists 33 outcome measures and 156 analyses, with 28 secondary outcomes posted. The original sample-size justification, detailed statistical plan, multiplicity approach, full model specification, and missing-data pattern are not reported in the registry record.