DS-5565 Phase III Study for Post-herpetic Neuralgia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for DS-5565 Phase III Study for Post-herpetic Neuralgia (NCT02318719), a randomized na study. The primary outcome is Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia.

2. Clinical Question

The clinical question is about change in a participant-reported pain measure over the treatment period. Participants recorded pain in an electronic diary once daily, describing their pain over the past 24 hours before taking study drug. The score ranged from 0, meaning no pain, to 10, meaning worst possible pain; higher scores indicated worse pain. The registry defines negative change values as improvement, with more negative values representing greater improvement.

The trial also included a 52-week open-label extension. A secondary outcome described change in Visual Analog Scale pain from baseline at Week 14 to Week 66 following DS-5565 administration. That extension outcome is distinct from the primary Week 14 ADPS question. Numerical results for either outcome are not reported in the registry record, so the relative results of the dose groups and placebo cannot be assessed from the recorded outcome description alone.

3. Trial Design

The registry describes a randomized, double-blind, parallel-group study comparing placebo with three daily DS-5565 dose groups. The official title identifies the trial as an Asian Phase 3 study, while the registry phase entry is listed as NA. The study was multicenter and included a 14-week placebo-controlled treatment period followed by a 52-week open-label extension. Its status is completed.

The intervention descriptions specify oral DS-5565 at 15 mg, 20 mg, or 30 mg per day. The 15 mg group had 2 weeks of titration and 12 weeks at a fixed dose; the 20 mg group had 1 week of titration and 13 weeks at a fixed dose; and the 30 mg group had 2 weeks of titration and 12 weeks at a fixed dose. The placebo description specifies 14 weeks. The registry reports total enrollment of 765, but does not report the number assigned to each primary-period group in the registry record recorded for this analysis.

The study began in 2015-01, and primary completion is recorded as 2017-05-25. The sponsor is Daiichi Sankyo Co., Ltd. The registry describes the study objective as investigating the efficacy and safety of DS-5565 compared with placebo in subjects with post-herpetic neuralgia. The primary outcome was change in ADPS from baseline to Week 14. The listed secondary outcome concerns VAS pain through Week 66 following DS-5565 administration in Asian participants. Further details about sites, eligibility criteria, allocation procedures, and conduct of the extension 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: This study included a double-blind phase where participants received DS-5565 (15 mg, 20 mg, or 30 mg) or placebo and an open-label extension phase where participants received DS-5565 (starting dose 5 mg).

Double-blind Phase

Reasons for not completing this period:

Open-label Extension Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Average daily pain score (ADPS) was assessed in the modified Intent-to-Treat Analysis Set.

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 in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia, measured over Baseline to Week 14.

The primary endpoint is change in the Average Daily Pain Score from baseline to Week 14. Participants recorded their pain once daily in an electronic diary, rating how their pain had felt over the previous 24 hours. The scale ran from 0, no pain, to 10, worst possible pain. The weekly ADPS was the average of the diary pain scores. The outcome description states that higher ADPS scores indicated worse outcome.

The endpoint is expressed as change from baseline, rather than as a Week 14 score alone. Negative changes represent improvement in average daily pain, and more negative changes represent greater improvement. This direction is important when reading group estimates: a negative change should not be mistaken for worsening simply because its numerical value is below zero.

Daily diary recording is intended to capture repeated reports of pain over time, while the weekly average provides a summary for comparison at the scheduled endpoint. In general, a continuous endpoint can describe both the direction and magnitude of change, but its interpretation depends on the scale, the comparison group, and the uncertainty around the estimate. The registry identifies the modified Intent-to-Treat Analysis Set as the population for ADPS assessment. It does not report the numerical baseline or Week 14 group summaries, treatment contrasts, confidence intervals, or p-values. Therefore, the endpoint definition is available, but the recorded information does not establish the size or precision of any group difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies ADPS as a continuous measure summarized by a mean and standard deviation. It describes a randomized, parallel-group, double-blind comparison of placebo with DS-5565 dose groups. It does not report the specific statistical model, the exact treatment contrasts, or the procedure used to calculate uncertainty. The methods below explain the general statistical ideas relevant to this kind of outcome; they should not be read as confirmation that a particular method was used in this trial.

What does a mean represent?

In general, a mean is an average that summarizes the values observed in a group. For a change-from-baseline outcome, a group mean describes the average direction and size of change among the participants included in that analysis. Here, the endpoint definition gives the direction: negative change represents improvement in ADPS, and more negative change represents greater improvement. A mean is a summary, not a description of every participant’s experience, and it can conceal variation in individual values.

What does a standard deviation add?

In general, a standard deviation describes how spread out individual observations are around their group mean. A smaller spread indicates that observations are more clustered near the mean, while a larger spread indicates greater variation. It is not the same as the uncertainty in the estimated mean or in a difference between groups. The registry identifies standard deviation as the endpoint’s dispersion measure, but numerical standard deviations are not reported in the registry record.

Why focus on a between-group contrast?

For a randomized comparison, the central statistical question is usually the difference in outcome between the intervention group and its comparator. In general, a contrast uses the groups’ outcome information together to estimate how their results differ. Comparing change within a DS-5565 group alone does not isolate the difference from the change observed with placebo. The registry record does not give numerical contrasts for the primary outcome, so the direction and magnitude of any between-group difference cannot be described.

What does a confidence interval communicate?

In general, a confidence interval expresses the uncertainty around an estimated quantity, such as a group difference. A narrower interval indicates greater precision under the assumptions of the method; a wider interval indicates less precision. The interval also helps readers judge which effect sizes remain compatible with the observed data and method. It is not a guarantee about the true effect, nor does it describe the range of individual participant outcomes. No confidence interval for the primary outcome is reported in the registry record.

What does a p-value address?

In general, a p-value relates the observed data to a specified statistical model and null hypothesis. It does not give the probability that a treatment is effective, quantify the size of an effect, or replace an estimate with an interval. Interpretation depends on the prespecified analysis and on whether multiple comparisons were considered. A primary-outcome p-value is not reported in the registry record, and the statistical plan underlying any test is not reported either.

Why can over-dispersion matter?

In general, over-dispersion arises when observed variability is greater than a statistical model expects. If a model underestimates variability, standard errors and intervals may be too small and tests may appear more conclusive than warranted. The possibility is especially relevant when a chosen model relies on assumptions about how variability behaves. The primary ADPS outcome is continuous and is described with a mean and standard deviation; the registry record does not identify a model or report an over-dispersion assessment. It would therefore be inappropriate to claim that over-dispersion was or was not present.

How should the design inform interpretation?

Randomization is intended, in general, to make the assigned groups comparable in expectation, while blinding can reduce the influence of knowledge about assignment on behavior, assessment, or reporting. These design features do not remove the need to examine outcome completeness, analysis choices, and uncertainty. The trial is recorded as randomized and double-blind, but allocation details and the operational blinding procedures are not reported in the registry record. The record also does not describe the statistical model used for the primary endpoint.

What can planning calculations tell readers?

In general, sample-size planning calculations illustrate how design assumptions relate to the amount of information a study would need to detect a chosen effect under a stated approach. They are not observed power, do not describe the results actually obtained, and do not establish that an effect exists. The planning assumptions recorded for this study refer to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect. The registry record does not report the planning calculation values or the study’s own sample-size justification in the registry record. Since the numerical observed effect is also not reported, no planning illustration can be interpreted as an estimate of the primary treatment result.

These concepts clarify what would be needed for a full statistical reading: group summaries, an explicit contrast, an uncertainty measure, and enough detail to understand the analysis population and methods. The registry record’s endpoint description supplies the outcome’s scale and direction, but does not supply those numerical results or methods.

10. Multiplicity, Missing Data and Analysis Populations

The primary ADPS outcome is described as having several categories or time points, and the record does not reduce it to one comparison. The registry also lists 3 analyses. It does not report the detailed analysis results, identify a single primary contrast among them, or describe a plan for controlling the chance of false-positive findings across multiple comparisons. Whether multiplicity adjustment was used is not reported in the registry record. Without that information, individual comparisons should not be treated as if they necessarily represented a single prespecified test.

The primary outcome population is the modified Intent-to-Treat Analysis Set. The registry record does not define the modifications to the Intent-to-Treat population, report the number included in each analysis, or explain how participants were handled if they did not contribute Week 14 diary data. The amount and pattern of missing ADPS data are not reported. The method used to address missing observations, if any, is not reported in the registry record.

In general, missing-data methods matter because the observed outcomes may not represent all randomized participants, particularly if the likelihood of missing data is related to pain, treatment, or tolerability. Different assumptions and methods can lead to different estimates. This general concern does not establish that missing data biased this trial; the record does not give enough information to assess that possibility.

The registry describes an open-label extension and a secondary VAS outcome through Week 66. These should be distinguished from the blinded Week 14 primary comparison. The analysis population, missing-data approach, and multiplicity handling for the extension outcome are not reported in the registry record.

11. 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: cellulitis (0.4%), pneumonia (0.4%), breast cancer (0.4%), gastric cancer (0.4%), hepatocellular carcinoma (0.4%).

For the placebo group and the DS-5565 15 mg/Day, 20 mg/Day, and 30 mg/Day groups, the serious adverse-event entries report 0 affected participants in each group. The listed numbers at risk are 303 for placebo, 152 for 15 mg/Day, 153 for 20 mg/Day, and 155 for 30 mg/Day. The open-label extension entry reports 20 affected participants among 237 at risk. Deaths are recorded as 0 in each of the blinded-period groups and 1 in the open-label extension.

Other adverse events are reported as affecting 45 participants in the placebo group, 44 in the 15 mg/Day group, 53 in the 20 mg/Day group, and 72 in the 30 mg/Day group. The open-label extension reports 99 affected participants. These are registry counts; they should not be interpreted as comparative rates without considering the relevant group sizes, period of observation, and reporting definitions. The extension is open-label and is not the same comparison as the blinded treatment period.

The registry lists cellulitis, pneumonia, breast cancer, gastric cancer, hepatocellular carcinoma, and hyperglycaemia among the serious-event terms, each reported as 0.4%. The record does not provide further context for interpreting those term percentages in this summary. Safety counts do not establish causation, and the entries do not provide enough information to compare event risk across treatment periods.

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

The record establishes that this was a randomized, double-blind, placebo-controlled study of oral DS-5565 in Asian participants with post-herpetic neuralgia. It describes a 14-week treatment period, a 52-week open-label extension, the ADPS primary endpoint, and the scale’s direction. It also records adverse-event counts. These details help define the clinical and statistical question the study set out to address.

The record does not report the numerical primary endpoint results. As a result, it does not show the ADPS mean changes by group, the estimated differences between DS-5565 and placebo, or the uncertainty around those comparisons. It does not allow a reader to determine from the recorded results whether groups differed, how large a difference might have been, or how precisely it was estimated. No conclusion about the primary efficacy comparison can be drawn from the endpoint description alone.

The outcome’s interpretation has a stated direction: negative ADPS change represents improvement, and more negative change represents greater improvement. That definition would help interpret results if numerical comparisons were available. It does not itself indicate that a change occurred or that groups differed. Nor would an observed change within a group, by itself, establish a treatment effect relative to placebo.

The safety entries describe counts in the blinded-period groups and in the open-label extension. They are not a substitute for the missing primary outcome estimates and should be interpreted in light of the different treatment periods and the registry’s reported group sizes. The record does not establish that any listed event was caused by treatment.

More broadly, a registry record is not a complete statistical report. Details such as the statistical model, multiplicity handling, missing-data methods, and operational definition of the modified Intent-to-Treat population are not reported. The appropriate reading is therefore bounded: the design and outcome definitions are described, but the central numerical efficacy results and several analysis details are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for pairing a randomized, double-blind, placebo-controlled design with a repeated participant-reported pain measure. Participants recorded pain daily, and ADPS summarized diary reports as a weekly average. That outcome structure makes the scale definition and the handling of repeated records important to understanding what a Week 14 change represents.

The endpoint is a continuous measure, summarized by a mean and standard deviation, and its direction is explicitly stated. Negative change represents improvement, which helps prevent a common interpretive error when reading change scores. The primary outcome population is also identified as a modified Intent-to-Treat Analysis Set, making the analysis population a relevant part of the statistical description.

The design includes three DS-5565 dose groups and placebo, followed by an open-label extension. That structure raises general questions about which treatment contrasts were central, how multiple comparisons were handled, and how the extension should be separated from the blinded randomized period. The registry record does not report enough statistical detail to resolve those questions, and it does not report the primary numerical comparisons.

This makes the distinction between an endpoint definition and an outcome result especially important. The record tells readers what was measured and when, but not the estimates needed to judge magnitude or precision. The safety entries provide event counts, but those counts answer a different question from the primary pain endpoint. A careful statistical reading preserves these distinctions rather than inferring results from the design or the stated study objective.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting efficacy is that numerical results for the primary ADPS outcome are not reported in the registry record. Group means, standard deviations, treatment contrasts, confidence intervals, and p-values are absent from the outcome information. The primary outcome entry also notes several categories or time points rather than a single reduced comparison, while detailed results for the listed analyses are not reported.

The registry identifies the modified Intent-to-Treat Analysis Set but does not define it or report its analysis size. The amount and pattern of missing diary data, the method for handling missing observations, and sensitivity analyses are not reported in the registry record. The model and other statistical methods used for the primary outcome are also not reported. Consequently, it is not possible to assess whether the analysis choices were robust to alternative assumptions.

The record does not describe multiplicity control across outcome categories, analyses, dose groups, or time points. It also does not report the study’s own sample-size justification. These omissions limit evaluation of the planning rationale and of how inferential claims should be interpreted across comparisons.

The safety entries give group counts, but additional details needed for fuller interpretation, including event definitions and further context for the listed event terms, are not reported in the registry record. The open-label extension is distinct from the blinded comparison, and the record does not provide extension analysis methods in the registry record. These limitations concern what is available in the registry record; they do not show that the trial lacked methods or analyses that may have been documented elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: DS-5565 Phase III Study for Post-herpetic Neuralgia — NCT02318719.
• Registry record last updated 2020-11-02; status last verified 2020-10.
• Results first posted 2020-11-02.
• 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

NCT02318719 is a completed randomized, double-blind, parallel-group study of DS-5565 versus placebo in Asian participants with post-herpetic neuralgia. The official title describes a Phase 3, multicenter study with a 14-week treatment period followed by a 52-week open-label extension. The registry phase entry is NA. Total enrollment is recorded as 765, and the sponsor is Daiichi Sankyo Co., Ltd.

The primary outcome is change in ADPS from baseline to Week 14, assessed in the modified Intent-to-Treat Analysis Set. Negative change represents improvement. The registry record does not report the numerical primary outcome results or the detailed statistical methods needed to interpret a treatment contrast. It records serious and other adverse-event counts for the blinded-period groups and the open-label extension. The design and outcome definitions are available, but the primary efficacy result is not reported in the registry record.