Japanese IP-TN Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Japanese IP-TN Trial (NCT02831569), a na phase 3 study. The primary outcome is Percentage of Patients With Drug-related Adverse Events [AEs].

2. Clinical Question

In statistical terms, the primary question is descriptive: how many participants in the treated group were recorded as having drug-related adverse events during the specified period? Because the trial had no control group, the result cannot estimate a difference in adverse-event risk between the combination and another treatment or no treatment. It also cannot distinguish events associated with the medication from events that might have occurred in the same population without it. The trial was open-label, so participants and investigators knew the treatment being given. The registry record does not report further details about how drug relationship was assessed.

3. Trial Design

The Japanese IP-TN Trial was a Phase III, open-label, single-group, multicentre study. Allocation was listed as not applicable, and masking was listed as none. The intervention was loxoprofen sodium/methocarbamol fixed dose combination tablets. The registry describes oral administration for 2 weeks, followed by a 1-week follow-up period.

The study was designed to confirm safety and efficacy in patients with low back pain, scapulohumeral periarthritis, or cervico-omo-brachial syndrome associated with muscle strain. The brief summary says that more than 90 patients would be screened to enroll approximately 80. Actual enrollment is listed as 80. The registry dates the study start to 2016-07-27 and primary completion to 2016-10-19; the status is completed.

After written informed consent, an investigator assessed eligibility. Patients who completed the procedures and assessments at the first visit received the trial medication and entered the open-label treatment period. Those who completed treatment entered follow-up and completed the trial after confirmation at the last visit or by phone interview. Further detail about visit timing or the precise assessment schedule is not reported in the registry record.

A single-group design can describe outcomes among enrolled participants, but it does not provide a concurrent control for comparison. The open-label design also means treatment assignment was known. These features matter when interpreting subjective assessments, adverse-event reporting, and claims about treatment effects. The registry record does not report the rationale for selecting this design, a formal sample-size justification, or a statistical analysis plan. The planning assumptions associated with a sample-size illustration should not be mistaken for the trial’s actual design: this trial had one group, not two equally allocated arms.

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

Analysis population for the primary outcome, as defined in the registry: Treated Set \[TS\]: The analysis set included patients who received at least one dose of the trial medication during the trial period. Safety analysis was performed on TS.

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: Treated Set \[TS\]: The analysis set included patients who received at least one dose of the trial medication during the trial period. Safety analysis was performed on TS.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patients With Drug-related Adverse Events [AEs], measured over Up to 3 weeks..

The primary endpoint is the percentage of participants with drug-related adverse events, assessed up to 3 weeks. It is a binary outcome at the participant level: a participant is counted as having the outcome if at least one qualifying event is recorded, rather than being counted once for every event. The primary outcome description identifies the endpoint as a percentage, while the registry’s adverse-event figures list the number at risk and the number affected.

The posted figures list 80 participants at risk and 0 affected for the loxoprofen sodium/methocarbamol fixed dose combination group. These are the recorded counts; no additional percentage needs to be inferred to understand the reported result. The safety analysis population was the Treated Set, which included patients who received at least one dose during the trial period.

Adverse-event endpoints are used to describe safety observations during a defined period of exposure and follow-up. A participant-level percentage can be easier to interpret than a total event count when some participants may experience more than one event. As a general statistical point, however, a low or zero observed count does not establish that the underlying risk is zero. Its precision depends on the amount of information in the data, and an interval estimate would help express that uncertainty. A confidence interval for this endpoint is not reported in the registry record.

The registry also lists a secondary pain assessment after 2 weeks. Its specific measurement method, analysis details, and result are not reported in the registry record, so that outcome cannot be interpreted from the recorded details available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each person is classified according to whether a drug-related adverse event was recorded during the defined period. A percentage summarizes the proportion of participants with that classification. The registry’s safety figures give the affected count and the number at risk, with 80 at risk and 0 affected in the listed group. The registry record does not provide a confidence interval or a detailed account of the calculation used for the percentage.

What does a confidence interval add?

As a general statistical explanation, a confidence interval describes the uncertainty around an estimate. It indicates which values remain reasonably compatible with the observed data under the method used. An estimate based on a finite group is not an exact measurement of the underlying event probability. This is especially important when no events are observed: zero in the study group does not by itself show that the probability in a broader population is exactly zero. No interval for this result is reported in the registry record, and no interval is calculated in this interpretation.

What can a single-group result establish?

A single-group study can report how many participants experienced an outcome while receiving the study medication. It cannot directly estimate a contrast with a control condition when no control group was enrolled. In a general explanation, comparative effects require information about outcomes under each of the conditions being compared, with a design and analysis that support that contrast. This trial’s allocation is listed as not applicable and its model as single group. Accordingly, the observed safety count is descriptive rather than a randomized comparison.

Open-label status is another design feature to keep in mind. As a general matter, knowing which intervention is being given can affect how symptoms are noticed, reported, or assessed. The registry record lists no masking. It does not describe the procedures used to attribute an event to the medication, so the role of those procedures cannot be evaluated from the registry information.

How should planning illustrations be read?

The record describes a sample-size planning illustration based on the observed effect. Its assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. These are assumptions for a planning exercise, not a description of the trial’s single-group design. The illustration is not observed power and does not show that the trial had a particular probability of detecting an effect. The registry record does not report the trial’s own sample-size justification. No planning count is reproduced.

More generally, a planning calculation depends on the outcome, the effect size one aims to detect, the error rate, the allocation, and the statistical method. For a binary outcome, assumptions about the event probability matter. When an observed event count is zero, using the observed result as a planning basis can be especially sensitive to the assumptions chosen. The planning illustration should therefore be distinguished from the observed safety data and from the protocol’s design rationale.

What analysis details remain unknown?

The registry lists 0 analyses. It does not report an inferential test, a model, adjustment variables, an interval method, or a missing-data procedure for the primary endpoint. It also does not report whether any interim analyses were planned or conducted. Those details cannot be inferred from the endpoint description or the reported counts. In general, the choice of method affects how uncertainty is summarized, while analysis-population definitions affect which participants contribute to a result. Here, the safety population is specified as the Treated Set, but further handling rules are not reported.

Over-dispersion is a general concern in some count-data models when variability exceeds what the model expects. It is not a directly reported feature of this participant-level binary endpoint, and the registry does not report a count-data model. The registry record therefore gives no basis for saying that over-dispersion was assessed or modeled. In general, statistical methods should match the outcome and design; method choices cannot be reconstructed from a single observed count.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Loxoprofen Sodium/Methocarbamol [FDC]")
n      <- c(80)
events <- c(6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Loxoprofen Sodium/Methocarbamol [FDC]  80  6  7.5  2.8  15.6  3.5  15.4  3.5  15.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary percentage of participants with drug-related adverse events and a secondary pain assessment after 2 weeks. It does not report a multiplicity adjustment or a strategy for controlling the chance of false-positive findings across outcomes. The analysis list contains 0 analyses, and the inferential procedures for either outcome are not reported in the registry record. The secondary outcome’s measurement details and result are also not reported in the registry record.

As a general statistical point, examining multiple outcomes can create more opportunities to identify an apparently notable result by chance. A prespecified hierarchy, adjustment, or other multiplicity strategy can clarify how findings should be interpreted. No such approach is reported, so it should not be assumed that one was used.

The primary safety analysis population is identified as the Treated Set. It includes patients who received at least one dose of trial medication, and the registry states that safety analysis was performed on this set. The adverse-event listing gives 80 at risk. The registry does not report how participants with incomplete follow-up, missing assessments, withdrawal, or other unavailable data were handled. It also does not provide a count of missing outcome observations or a missing-data analysis.

In general, the treatment of missing data can affect a reported percentage because the denominator and the assumptions about unavailable outcomes matter. No missing-data method or sensitivity analysis is reported in the registry record, so the robustness of the endpoint to missing observations cannot be assessed from the recorded information. These omissions do not establish that data were missing; they mean the registry record does not describe their status or handling.

12. 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 5% reporting threshold.

The serious adverse-event listing gives 80 participants at risk and 0 affected in the loxoprofen sodium/methocarbamol group. It lists no serious event terms. These are the recorded serious-event figures for the listed group; they should be read as observed counts, not as a guarantee that serious events cannot occur. The death count is not reported in the registry record.

The listing also gives 80 at risk and 0 affected for other adverse events. The primary endpoint, however, is specifically the percentage of participants with drug-related adverse events. The registry’s serious-event figures should not be treated as interchangeable with that endpoint: seriousness and attribution to the drug are distinct classifications. The record does not give further detail about the relationship between these categories or the criteria used to classify events.

As a general statistical point, a zero count is compatible with uncertainty about the underlying event frequency, particularly when interpreting results beyond the participants observed. A confidence interval for the serious adverse-event result is not reported in the registry record. The trial included a 2-week treatment period and a 1-week follow-up, and the primary outcome timeframe is listed as up to 3 weeks. The counts therefore describe the stated trial observation period, not risk over an unreported longer period.

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

The result means that the registry’s listed safety data recorded 0 participants with drug-related adverse events among 80 at risk in the Treated Set. It is a finding about the participants enrolled and observed in this single-group, open-label trial, under the endpoint definition and assessment period recorded. It is useful as a description of what was observed in this trial.

It does not mean that the underlying probability of a drug-related adverse event is zero. A study can observe no events while uncertainty about the event probability remains. The registry record does not report a confidence interval, so the precision of the estimate cannot be assessed from an interval. The result also does not establish that the medication caused or prevented any event, because the study did not include a comparator group.

The finding does not answer a comparative safety question. No treatment-versus-control estimate, relative effect, or controlled contrast can be obtained from a single group alone. Nor can the primary safety result answer the efficacy question: although the registry lists a secondary pain assessment after 2 weeks, its measurement details and result are not reported in the registry record.

The result also should not be interpreted as a full account of every possible safety outcome. The posted figures include zero affected for other adverse events, but the event descriptions and further safety details are not reported in the registry record. Serious-event counts are listed separately, and the death count is not reported in the registry record. The registry’s limited descriptions do not permit a complete assessment of event severity, timing, or attribution.

In general, interpreting a safety estimate involves considering the observed count, the denominator, the observation period, the analysis population, and the uncertainty around the estimate. Here, the Treated Set definition, group count, and timeframe are stated, but an interval estimate and detailed assessment procedures are not. The most defensible reading is therefore narrow: no drug-related adverse events were recorded in the listed treated group during the specified observation period, while the precision and comparative implications remain undetermined.

14. Why This Trial Matters Statistically

This trial illustrates why study design determines the kind of statistical question that can be answered. Although it is a Phase III study, it is single-group and open-label, with no comparator. Its safety figures can describe the enrolled treated participants, but they do not estimate a difference between interventions. The design label alone cannot supply a comparative interpretation that the data structure does not support.

The primary endpoint also highlights the distinction between an observed count and an underlying event probability. The record lists 0 affected participants among 80 at risk. That is a clear description of the observed result, but without an interval estimate it does not convey the precision of the estimated risk. General statistical reasoning cautions against treating a zero observed count as proof of zero underlying risk.

The trial also illustrates why analysis populations matter. The safety outcome applies to the Treated Set, defined by receipt of at least one dose, rather than being described simply as a result for everyone screened or considered for enrollment. The registry record lists 80 enrolled and 80 at risk for the adverse-event group, but it does not provide further detail on missing assessments or follow-up completeness.

Finally, the record distinguishes observed results from planning assumptions. Its sample-size illustration uses assumptions involving two arms, while the actual trial is single-group. A planning illustration is not the study design, a justification for the actual enrollment, or observed power. Keeping these concepts separate helps prevent hypothetical calculations from being mistaken for evidence generated by the trial.

15. 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 primary limitation for interpretation is the absence of a comparator. The single-group design cannot separate outcomes observed during the trial from what might have occurred under another condition. Open-label status is also relevant to the observation and assessment of outcomes. The registry record does not report masking or blinded event adjudication; masking is listed as none.

The primary safety result is a zero affected count among 80 at risk, but the registry does not report a confidence interval or other measure of precision. It also does not report detailed criteria for determining whether an adverse event was drug-related. These gaps limit interpretation of both uncertainty and attribution.

The registry record does not report the trial’s own sample-size justification, an inferential statistical plan, interim analyses, or a method for handling missing data. It lists 0 analyses. Although the safety population is defined as the Treated Set, details about incomplete follow-up and missing outcome observations are not reported in the registry record.

The secondary pain assessment is named, but its specific measure, analysis details, and results are not reported in the registry record. The available safety counts therefore cannot be used to draw conclusions about that outcome. The death count is also not reported in the registry record, and adverse-event terms beyond the indication that no serious event terms are listed are not described.

The observation period is limited to the stated treatment and follow-up schedule, with the primary outcome timeframe listed as up to 3 weeks. The registry record does not provide evidence about outcomes beyond that period. These limitations restrict conclusions to the recorded participants, outcomes, and timeframe; they do not establish that unreported events or analyses did or did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Japanese IP-TN Trial — NCT02831569.
• Registry record last updated 2018-07-20; status last verified 2017-10.
• Results first posted 2018-07-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The Japanese IP-TN Trial was a completed Phase III, open-label, single-group, multicentre study of loxoprofen sodium/methocarbamol fixed dose combination tablets. Enrollment was 80. The registry lists a 2-week treatment period and a 1-week follow-up period for patients with low back pain, scapulohumeral periarthritis, or cervico-omo-brachial syndrome associated with muscle strain.

The primary outcome was the percentage of participants with drug-related adverse events, assessed up to 3 weeks. The safety analysis used the Treated Set. The adverse-event listing records 0 affected among 80 at risk for the combination group. The registry also lists a secondary pain assessment after 2 weeks, but its result is not reported in the registry record.

The single-group design supports a descriptive reading of the recorded outcome, not a controlled comparison. A confidence interval, missing-data procedure, detailed statistical plan, and the trial’s own sample-size justification are not reported in the registry record.