Study to Assess the Efficacy, Safety, and Tolerability of ADL5747 in Participants With Postherpetic Neuralgia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess the Efficacy, Safety, and Tolerability of ADL5747 in Participants With Postherpetic Neuralgia (NCT01058642), a randomized phase 2 study. The primary outcome is Change in Weekly Average Numeric Pain Rating Scale (NPRS) Score From Baseline to End of Treatment (Week 2 of Each Treatment Period).

2. Clinical Question

3. Trial Design

This was a Phase 2A randomized, quadruple-masked, two-period crossover study with placebo and active control. It was designed to assess analgesic efficacy, safety, tolerability, and pharmacokinetics of ADL5747 in participants with postherpetic neuralgia. The reported enrollment was 41. The registry lists the study as terminated and states that it ended early because of lack of efficacy of ADL5747.

In a crossover design, participants receive treatments in separate periods rather than being assigned to a single treatment for the entire study. This can allow comparisons that account for differences between participants, because a participant may contribute information under more than one treatment. That benefit depends on suitable conduct and analysis. Period effects, treatment order, and carryover from one treatment into a later period are issues that may matter in crossover studies. The registry record does not report the planned treatment sequences or the statistical approach for these issues.

ADL5747 was described as 150 mg orally twice daily for 14 days during one of the two treatment periods. Placebo was given orally twice daily for 14 days during one treatment period, and the record also describes placebo twice daily during a 14-day washout between Treatment Period 1 and Treatment Period 2. Pregabalin was included as an active control. Its description includes 75 mg twice daily for the first 3 days and 150 mg twice daily for the last 11 days of a 14-day treatment period; the remainder of that description is incomplete in the registry record.

The registry identifies the masking as quadruple but does not identify the roles of the masked parties. Details of randomization, sequence allocation, adherence, and the intended analysis population are not reported in the registry record. These omissions limit what can be reconstructed about implementation and planned analysis.

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.

Treatment Period 1

Reasons for not completing this period:

Washout Period

Treatment Period 2

Analysis population for the primary outcome, as defined in the registry: Zero participants were analyzed, and no data was collected for this measure. Due to lack of efficacy of ADL5747, the study was terminated early.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: All randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Change in Weekly Average Numeric Pain Rating Scale (NPRS) Score From Baseline to End of Treatment (Week 2 of Each Treatment Period), measured over Baseline, Week 2 of Treatment Period 1 or 2.

The primary endpoint was change in weekly average Numeric Pain Rating Scale score from baseline to the end of treatment, defined as Week 2 of each treatment period. The NPRS is an 11-point scale from 0, indicating no pain, to 10, indicating the worst possible pain. For this measure, the mean of daily average scores was calculated from pain assessments collected up to 3 times per day over a 7-day period.

A pain rating scale can summarize a participant’s reported symptom intensity in a form that can be compared over time. A change score focuses on how the rating at the end of a treatment period differs from the baseline rating, rather than only describing the end value. The registry record does not describe the baseline definition in further detail, the planned method for combining individual observations into a treatment comparison, or a threshold for interpreting a change as important.

These measurement details do not produce an efficacy result on their own. The registry states that zero participants were analyzed for this endpoint and no data were collected. Consequently, there is no posted average change, treatment contrast, or uncertainty estimate to interpret. The endpoint’s stated purpose can be described, but its observed behavior in this study cannot be assessed from the registry results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, quadruple-masked, and crossover. Those design labels describe features of the trial, not the statistical analysis. Randomization is intended to allocate treatment assignments through a chance-based process, helping prevent deliberate or systematic assignment based on participant characteristics. The registry does not describe the randomization procedure, the allocation sequence, or how treatment order was generated.

What does crossover mean for a treatment comparison?

In a crossover study, treatments are given in distinct periods. A participant may therefore contribute observations under more than one treatment. In general, comparing a participant with themselves can reduce the influence of stable differences between participants. It does not remove every source of uncertainty. Outcomes may change over time for reasons unrelated to treatment, and treatment in an earlier period may influence a later period. These are commonly described as period and carryover concerns. The registry reports a washout period between Treatment Period 1 and Treatment Period 2, but does not report how the analysis was to account for period, sequence, or carryover effects. The presence of a washout alone does not show how those issues were evaluated.

What does masking tell us?

The registry calls the study quadruple-masked. Masking can reduce the risk that knowledge of treatment assignment affects participant reports, clinical conduct, or assessment. However, the registry record does not identify which parties were masked or describe how masking was maintained. The design label therefore conveys that masking was planned or used, but does not establish the success of masking in practice.

How is the endpoint constructed?

The endpoint uses the NPRS, an 11-point scale whose endpoints are 0 for no pain and 10 for the worst possible pain. Daily average scores were formed from pain assessments obtained up to 3 times per day over a 7-day period, and the mean of daily averages was used for the weekly average. The primary outcome then describes change from baseline to the end of treatment at Week 2 of each period. This summarizes repeated symptom ratings rather than relying on a single assessment. The registry does not report additional details about the baseline calculation, how incomplete daily observations would be handled, or the exact treatment contrast planned.

What would a treatment estimate and confidence interval show?

In general, a treatment estimate summarizes the observed contrast between treatments for the chosen endpoint. A confidence interval describes the range of values reasonably compatible with the data and the analysis assumptions. A narrower interval indicates greater precision than a wider interval, but neither the estimate nor its precision can be assessed without endpoint results. No primary outcome values, treatment estimate, or confidence interval are posted in this record.

What is the role of a significance test?

In general, a significance test evaluates how compatible the data are with a specified null hypothesis, conditional on the test assumptions. A p-value is not a measure of the size or clinical importance of an effect, and it does not replace an estimate with an uncertainty interval. The registry record does not report a primary endpoint p-value or the planned test. It is therefore not possible to infer a statistical conclusion from the posted primary outcome information.

What does the planning illustration represent?

The sample-size section is a planning illustration, not a description of the study’s actual design justification and not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. The registry does not report the trial’s own sample-size justification. Moreover, because the primary endpoint has no collected data, the record does not provide an observed endpoint effect that can be independently assessed. Planning calculations describe hypothetical design requirements under assumptions; they do not establish that a trial had a particular probability of detecting an effect after completion.

For outcomes that are counts, variability can sometimes exceed what a simple model assumes. In general, over-dispersion means that the observed variation is greater than the model’s expected variation; ignoring it can make uncertainty appear too small. This concept is not a reported feature of this pain endpoint, and the registry does not report a model or dispersion estimate for it. The primary endpoint is unavailable, so there is no basis in this record to assess model fit, residual variation, or the suitability of any particular analysis.

Overall, the design labels and endpoint definition describe the intended framework. The statistical analysis plan, treatment contrast, handling of crossover effects, missing-data procedures, and analysis population are not reported in the registry record. No numerical primary outcome analysis is available to validate against that framework.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the change in weekly average NPRS score from baseline to the end of treatment. Its timeframe refers to Week 2 of Treatment Period 1 or 2, while the study includes ADL5747, placebo, and pregabalin. The record does not present a single reduced comparison for these possible treatment and period combinations. The analysis display consequently does not summarize a primary comparison.

Multiplicity arises in general when several hypotheses, endpoints, time points, or treatment comparisons are tested. Testing multiple questions can increase the chance of at least one apparently unusual result, so a statistical plan may specify which comparison is primary and whether adjustments or a testing hierarchy are used. The registry record does not report a multiplicity strategy, an ordering of comparisons, or an adjustment procedure. This does not establish that no such plan existed; it means the plan is not reported in the registry record.

The record states that zero participants were analyzed and that no data were collected for the primary measure. That leaves no observed primary endpoint values from which to examine missingness, exclusions, or the difference between enrolled and analyzed participants. The reason no data were collected is stated as early termination due to lack of efficacy of ADL5747. The registry does not describe whether any partial endpoint observations existed outside the primary outcome record or how such observations would have been handled.

Missing-data methods, analysis populations, and rules for including participants in the primary analysis are not reported in the registry record. There is no basis for inferring an intention-to-treat analysis, a per-protocol analysis, imputation, or another approach. The absence of collected endpoint data should not be interpreted as evidence that missingness was handled successfully or that the endpoint was complete; it means the efficacy analysis cannot be evaluated from the posted information.

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 registry reports serious adverse events for three treatment groups. For ADL5747, 0 of 18 participants at risk were reported as affected; for placebo, 0 of 38; and for pregabalin, 0 of 19. These are group-specific counts. Because the trial used a crossover design, the group denominators should not be treated as separate counts of unique people or added to infer the number of participants enrolled.

The registry also reports other adverse events: 4 of 18 participants at risk in the ADL5747 group, 7 of 38 in the placebo group, and 9 of 19 in the pregabalin group. These counts are not the primary efficacy outcome. The record does not provide event-level terms for these other events in the information, nor does it give a basis for attributing them to a treatment. A count of participants affected is not the same as a count of event episodes.

Death counts are not reported in the registry record. The zero serious-event counts indicate that no affected participants were reported in these group summaries; they do not establish the absence of every possible safety concern. The posted information does not include enough detail to compare risks statistically or to interpret differences as causal.

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

The record documents a randomized, masked crossover study of ADL5747, placebo, and pregabalin in participants with postherpetic neuralgia. It specifies a primary pain-rating outcome and reports enrollment of 41. It also states that the trial was terminated early due to lack of efficacy of ADL5747. These registry entries describe the study and its reported status, but they do not amount to a numerical estimate of treatment effect.

The primary outcome record says zero participants were analyzed and no data were collected for the measure. As a result, the posted results cannot show how NPRS scores changed under any treatment, how the treatments compared, or how precise a comparison might have been. Readers cannot infer a direction or magnitude of an effect from the endpoint data, because no endpoint data are posted. The stated termination reason should not be converted into an unreported treatment estimate or a statistical test result.

The safety summaries report zero participants with serious adverse events in each of the three groups, alongside counts for other adverse events. Those figures describe the registry’s group summaries; they do not establish that a treatment caused or prevented an event, and they do not answer the primary efficacy question. Death counts are not reported in the registry record.

In general, absence of a posted result is different from a result showing no effect. It prevents assessment of the observed effect and its uncertainty. Likewise, a planning illustration is not observed power and cannot fill the gap left by missing endpoint results. The record supports a careful description of what was planned and what was reported, but not a quantitative conclusion about analgesic efficacy.

13. Why This Trial Matters Statistically

This trial illustrates why a registry record must be read at more than one level. The design and endpoint fields describe the intended scientific question, while the results fields determine whether that question can be answered from posted data. Here, the record specifies a weekly average NPRS change outcome and a crossover comparison, but says that no primary outcome data were collected and no participants were analyzed for that measure.

That distinction matters statistically because an endpoint definition is not an endpoint result. A scale, a schedule of assessments, and a treatment plan do not supply an effect estimate or its precision. Without those results, neither a confidence interval nor a hypothesis test can be interpreted, and the reason given for early termination cannot serve as a substitute for a quantitative comparison.

The study also shows why a crossover design requires analysis details. In general, within-participant comparisons can be useful, but conclusions depend on how periods and treatment sequences are handled and whether carryover is a concern. The record identifies the crossover model and a washout period but does not report the statistical plan. That gap limits assessment even before considering the absence of outcome data.

Finally, safety and efficacy summaries answer different questions. The serious adverse event counts and other adverse event counts are descriptive information, not evidence about the primary pain endpoint. Keeping those evidence types separate avoids overstating what the registry can establish. The main statistical lesson is straightforward: when outcome data are unavailable, the scientifically responsible interpretation is to describe the missing result and the limits it creates, rather than infer an effect from study labels or termination status.

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 explicit: zero participants were analyzed for the primary outcome, and no data were collected for that measure. There is no posted change in NPRS score, treatment contrast, estimate of variability, confidence interval, or test result. The registry’s statement that the study was terminated early due to lack of efficacy of ADL5747 does not provide those missing quantities.

The record gives an enrollment of 41, but it does not explain the relationship between enrollment and completion of the treatment periods or provide participant flow for the primary analysis. The analysis population and the intended handling of participants who did not complete a period are not reported in the registry record. Consequently, the enrollment figure cannot be used to infer the number contributing to each treatment comparison.

Important design and analysis details are also absent. The registry does not report treatment sequence allocation, the full statistical plan, how period or carryover effects would be handled, multiplicity procedures, or missing-data methods. It identifies quadruple masking without identifying the masked roles. The pregabalin arm description is incomplete, so its full dosing sequence is not available in the record.

The safety information is limited to group counts for serious and other adverse events. Event-level detail for the other adverse events, attribution, and death counts are not reported in the registry record. These limits prevent detailed safety comparisons and causal interpretation. Taken together, the posted information permits description of the trial framework and selected safety counts, but not a quantitative assessment of the primary efficacy question or a complete reconstruction of trial conduct and analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Assess the Efficacy, Safety, and Tolerability of ADL5747 in Participants With Postherpetic Neuralgia — NCT01058642.
• Registry record last updated 2015-07-30; status last verified 2015-07.
• Results first posted 2015-07-08.
• 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

NCT01058642 is a Phase 2A randomized, quadruple-masked, two-period crossover study of ADL5747 in participants with postherpetic neuralgia, with placebo and pregabalin as comparators. Reported enrollment was 41, and the registry lists the study as terminated.

The primary outcome was change in weekly average NPRS score from baseline to Week 2 of each treatment period. The registry states that the study ended early due to lack of efficacy of ADL5747, but also reports that zero participants were analyzed and no primary outcome data were collected. No quantitative efficacy result is therefore available in the record.

Serious adverse events were reported for 0 of 18 participants at risk with ADL5747, 0 of 38 with placebo, and 0 of 19 with pregabalin. Other adverse event counts were 4 of 18, 7 of 38, and 9 of 19, respectively. Death counts are not reported in the registry record. Statistical analysis details, including the treatment comparison and missing-data methods, are not reported.