This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Compare Safety and Efficacy of Tramadol Hydrochloride/Acetaminophen With Gabapentin in Participants With Diabetic Neuropathy (NCT00634543), a randomized phase 4 study. The primary outcome is Change From Baseline in Pain Intensity Score at Day 43.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00634543 |
| Phase | Phase 4 |
| Condition | Diabetic Neuropathy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 162 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Janssen Korea, Ltd., Korea |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned participants with diabetic neuropathy and painful diabetic neuropathy. The primary analysis population was the full analysis set (FAS): randomly assigned participants who met the eligibility criteria and had at least one post-baseline efficacy assessment. The registry does not report participant characteristics such as age, sex, baseline pain distribution, or duration of diabetic neuropathy, so the population’s clinical profile cannot be described further from the record.
Intervention
The intervention was tramadol hydrochloride (HCl) with acetaminophen. The registry describes an escalating schedule beginning with 1 tablet containing tramadol HCl 37.5 mg and acetaminophen 325 mg once daily at bedtime, followed by twice-daily and then thrice-daily administration during the stated early treatment period. The description says dosage could be increased if there was no pain relief, but the recorded schedule is truncated and does not give the complete escalation details.
Comparator
The comparator was gabapentin. Its recorded schedule begins at 300 mg once daily, then increases to twice daily and thrice daily, with a later schedule including 300 mg in the morning and midday and 600 mg in the evening. The registry description is truncated before the complete dosing information is available. The trial was randomized, parallel-group, and open-label, so participants and study personnel were not masked to assigned treatment.
Primary question
The stated primary endpoint was change from baseline in pain intensity score at Day 43. Pain intensity was assessed using an 11-point numerical rating scale, from 0=no pain to 10=pain as bad as you can imagine. The registry record does not report the treatment-group means, standard deviations, an estimated between-group effect, confidence intervals, or a single primary comparison. It therefore does not establish from the posted primary outcome data how the groups compared on this measure.
3. Trial Design
This was a Phase 4, randomized, open-label, parallel-group study sponsored by Janssen Korea, Ltd., Korea. It compared tramadol hydrochloride/acetaminophen with gabapentin in participants with diabetic neuropathy, with the stated purpose of evaluating effectiveness and safety for painful diabetic neuropathy. The registry lists enrollment of 162 and marks the study completed. The recorded study dates are a start in 2006-12 and primary completion in 2008-10.
Random allocation is intended to reduce systematic differences between treatment groups at entry by using chance to assign participants. It does not guarantee that the groups are identical on every baseline characteristic, and the registry does not report a detailed baseline profile. The parallel design means the comparison was between groups assigned to different study treatments, rather than a record of each participant switching between treatments.
The study was open-label, with masking listed as none. Participants and study personnel could therefore know the assigned treatment. In general, awareness of treatment assignment can influence subjective reports, treatment expectations, interactions with study staff, and assessments that involve judgment. Pain intensity is participant-reported, so the open-label feature is relevant when interpreting a pain-score comparison. It does not by itself establish that reported scores were biased; the registry does not report an assessment of such bias.
The treatment descriptions give dose schedules for both study drugs, including an allowance for dose increases if pain relief was absent. However, those descriptions are cut off before the full dosing instructions are recorded. The registry record does not report adherence, treatment discontinuation, use of additional pain treatments, or the extent to which participants followed the scheduled dosing. It also does not report details of the randomization procedure or allocation concealment.
The registry lists secondary outcomes involving pain relief, participant and investigator overall assessments of study medication, and changes in Brief Pain Inventory and Short Form-36 scores at Day 43. These outcomes provide different perspectives on pain, treatment assessment, and health status. Their presence does not substitute for the missing primary-group estimates, and the record does not report enough outcome results to describe the comparative findings across these measures.
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
| Stage | Tramadol Hydrochloride/ Acetaminophen | Gabapentin |
|---|---|---|
| STARTED | 78 | 84 |
| Treated | 76 | 80 |
| COMPLETED | 59 | 63 |
| NOT COMPLETED | 19 | 21 |
Reasons for not completing this period:
| Reason | Tramadol Hydrochloride/ Acetaminophen | Gabapentin |
|---|---|---|
| Other | 1 | 2 |
| Protocol Violation | 3 | 3 |
| Adverse Event | 11 | 11 |
| Withdrawal by Subject | 4 | 4 |
| Lost to Follow-up | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) included all randomly assigned participants who met the eligiblility criteria and had at least 1 post-baseline efficacy assessment data. Last observation carried forward (LOCF) was used.
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: Full analysis set (FAS) included all randomly assigned participants who met the eligibility criteria and had at least 1 post-baseline efficacy assessment data.
| Characteristic | Unit | Tramadol Hydrochloride/ Acetaminophen | Gabapentin | Total |
|---|---|---|---|---|
| Participants analysed | 71 | 76 | 147 | |
| Age Continuous | Years | 58.2 (SD 7.4) | 56.6 (SD 9.3) | 57.4 (SD 8.4) |
| Sex: Female, Male: Female | Participants | 34 | 45 | 79 |
| Sex: Female, Male: Male | Participants | 37 | 31 | 68 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Pain Intensity Score at Day 43, measured over Baseline and Day 43.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in pain intensity score at Day 43. Pain intensity was measured on an 11-point numerical rating scale, with 0 representing no pain and 10 representing pain as bad as you can imagine. The scale is intended to represent a participant’s reported pain intensity; change from baseline describes how that score differs from the participant’s starting score over the specified assessment period.
In general, a change score can help describe whether reported pain intensity shifted during a study, while a comparison between randomized groups can estimate how those changes differed under the assigned treatments. That comparative estimate, rather than a change within either group alone, is generally the relevant quantity for assessing a randomized treatment contrast. A measure’s clinical meaning also depends on how changes are distributed and on the uncertainty around the estimated comparison.
The registry states that the endpoint summary parameter was the mean and that dispersion was to be described with a standard deviation. A mean describes the central value of a group’s scores; a standard deviation describes how spread out individual scores are around that mean. These summaries do not reveal the actual findings without the reported group estimates and comparison. Those values, along with a confidence interval or test result for the primary comparison, are not reported in the registry record.
The recorded analysis population was the FAS, with last observation carried forward (LOCF) used. The registry does not give further detail about the timing or handling of missing pain assessments beyond that description. Consequently, the endpoint definition is clear at a broad level, but the posted record does not permit a numerical interpretation of the primary treatment contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record identifies a clinically relevant comparison: pain intensity after assignment to tramadol HCl/acetaminophen or gabapentin in participants with painful diabetic neuropathy. It also specifies the measurement scale, the Day 43 assessment, the mean as the summary parameter, and standard deviation as the dispersion measure. These details explain what the primary endpoint was intended to capture.
However, the registry record does not report the primary outcome values by treatment group. It does not give mean changes, standard deviations, a between-group estimate, a confidence interval, or a p-value for a single primary comparison. The record explicitly indicates that the primary outcome has several categories or time points and was not reduced to one comparison. As a result, the posted information does not support a numerical statement about the direction, size, or precision of the primary treatment contrast.
That absence matters. A reported within-group change would not, by itself, show whether one treatment produced a different change than the other. A treatment comparison requires an estimate of the contrast between groups and information about its uncertainty. Without those results, it is not possible to assess whether the observed group difference, if any, was small or large, or whether the data were compatible with a range of possible effects. The registry record also does not report a threshold for interpreting a change as clinically important.
The design characteristics help frame, but do not resolve, this uncertainty. Randomization is intended to support a fair comparison by limiting systematic allocation differences. The open-label design leaves subjective outcomes potentially susceptible to expectations or reporting effects. Neither feature tells the reader what the primary result was, and neither should be treated as a replacement for the missing estimate.
The registry lists secondary outcome categories, including pain relief, overall assessments of medication, and changes in other measures at Day 43. The record does not include numerical results for these outcomes in the registry record for this analysis. Their listing alone does not establish a favorable or unfavorable finding. It also does not resolve the lack of a single primary comparison.
Safety entries report zero serious adverse events in each treatment group, alongside other adverse-event counts of 33 for tramadol HCl/acetaminophen and 18 for gabapentin. These are descriptive counts, not evidence of a causal difference on their own. The registry does not report event definitions, severity distributions for the non-serious category, or a comparative statistical analysis of safety outcomes. Death counts are not reported in the registry record.
Overall, the available record supports a description of the trial’s purpose, design, endpoint, and selected safety counts. It does not provide the primary efficacy estimates needed to quantify or judge the treatment comparison. No conclusion that either treatment performed better or worse follows from the endpoint description alone.
9. Statistical Methods Explained
What does the primary endpoint represent?
The endpoint is change from baseline in pain intensity score at Day 43, summarized with a mean and standard deviation. In general, a change score represents the difference between a later measurement and a baseline measurement. The mean gives a group-level summary, while the standard deviation describes variability among individual scores. Neither statistic alone describes the estimated difference between randomized groups.
For a randomized comparison, the treatment contrast is generally the difference between the groups’ outcomes under the chosen analysis. A confidence interval is a way to express the statistical uncertainty around an estimated contrast: it indicates a range of values that are compatible with the data and the assumptions of the method. A narrower interval indicates greater precision than a wider interval, all else equal. The registry record does not report a primary contrast or confidence interval, so precision cannot be assessed from the primary outcome information recorded.
What does randomization contribute?
Randomization assigns participants by chance rather than by clinical choice. In general, this helps make treatment groups comparable with respect to measured and unmeasured characteristics at the time of assignment, though chance imbalances can remain. The registry identifies the allocation as randomized but does not report the sequence-generation method, allocation concealment, or baseline characteristics. It is therefore possible to describe the intended role of randomization, but not to evaluate its implementation in detail from this record.
The parallel model means participants were allocated to a treatment group for the study comparison. The record does not report a crossover design. With an open-label study, participants and personnel were not masked to assignment. In general, masking can reduce the influence of treatment expectations on subjective reporting and assessment. Its absence is especially relevant to a self-reported pain scale, although the presence of this risk does not prove that results were biased.
What does the FAS and LOCF description mean?
The registry defines the full analysis set as randomly assigned participants who met eligibility criteria and had at least one post-baseline efficacy assessment. It states that last observation carried forward was used. In general, LOCF replaces a missing later measurement with that participant’s last observed measurement. This approach can keep participants with incomplete follow-up in an analysis, but it relies on an assumption that the last measurement is a reasonable stand-in for an unobserved later value. That assumption may be implausible if symptoms change after the last observed assessment, and LOCF can understate or overstate uncertainty depending on the setting.
The record does not report how many participants lacked Day 43 values, the reasons for missing measurements, or whether sensitivity analyses were conducted. It also does not report other missing-data methods. Without those details, the likely influence of missing observations cannot be assessed. The FAS definition also differs from an analysis of every randomized participant because eligibility and a post-baseline assessment are specified as inclusion conditions.
What statistical test was used?
The registry record does not report the test or model used for the primary outcome, whether covariates were included, how repeated measurements or multiple time points were handled, or the exact contrast used. The fact that the outcome was summarized by a mean and standard deviation does not establish which inferential procedure was applied. A reader should not infer a t-test, analysis of covariance, or another method from those descriptive statistics alone.
In general, a statistical test evaluates how compatible observed data are with a specified null hypothesis under a model. A p-value is not a measure of the size or clinical importance of an effect, and it does not give the probability that a hypothesis is true. An estimated effect and confidence interval are typically more informative about magnitude and precision. No primary p-value, effect estimate, or interval is reported in the registry record.
How should planning assumptions be understood?
The record describes a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. It says the target effect is a stated fraction of the observed effect. In general, such calculations estimate how many participants per arm might be needed under specified assumptions to attain a chosen power for a future or hypothetical design. They are planning illustrations, not observed power and not evidence that the original trial was designed using those assumptions.
The record does not report the trial’s own sample-size justification or enough primary outcome results to interpret an observed-effect-based illustration. The illustration’s assumptions also do not establish that the original analysis used the normal approximation, equal allocation, or the stated significance threshold. A planning calculation depends on the assumed effect, variability, allocation, and testing framework; changing those assumptions can change the required sample size. The calculation should not be treated as a result about treatment effectiveness.
What do multiple outcomes imply?
The registry lists multiple outcome measures and analyses, including secondary assessments of pain relief, medication ratings, and changes in other health measures. In general, testing multiple outcomes or time points raises a multiplicity issue: the chance of finding at least one apparently unusual result can increase when many statistical tests are considered. Adjustment procedures can control some forms of this risk, but they may also change the interpretation or precision of individual comparisons.
The registry record does not report a multiplicity strategy, hierarchy among outcomes, or a prespecified single primary contrast. The noted issue that the primary outcome has several categories or time points and was not reduced to one comparison is particularly important: it prevents a clear, singular primary estimate from being identified in the posted results. The record does not report whether the categories or time points were analyzed separately or combined using another approach.
10. Multiplicity, Missing Data and Analysis Populations
The record lists a primary pain-intensity outcome and secondary outcomes covering pain relief, participant and investigator assessments of study medication, and changes in Brief Pain Inventory and Short Form-36 scores at Day 43. It also indicates six outcome measures and six analyses. The registry record does not report how those outcomes were prioritized, whether a formal hierarchy was used, or whether multiplicity adjustments were applied.
In general, multiplicity arises when several outcomes, time points, or statistical comparisons are assessed. Without an appropriate plan, interpreting isolated statistically significant findings can overstate the strength of evidence. A prespecified primary comparison and a stated adjustment strategy help clarify which result is confirmatory and how other results should be interpreted. Here, the registry notes that the primary outcome has several categories or time points and was not reduced to one comparison. No single primary estimate can therefore be identified from the recorded information.
For missing data, the FAS included randomly assigned participants meeting eligibility criteria who had at least one post-baseline efficacy assessment, and LOCF was used. In general, LOCF carries the last observed value forward to replace a missing later value. Its validity depends on assumptions about how the outcome would have changed after the last measurement. The record does not report the amount or reasons for missing outcome data, whether missingness differed between groups, or whether sensitivity analyses were performed.
The registry record does not describe an intention-to-treat analysis of all randomized participants, a per-protocol analysis, or other analysis populations. It also does not report the statistical method for the primary outcome or the analysis population used for each secondary outcome. These omissions limit evaluation of how missingness, multiple outcomes, and analysis choices may have affected the reported findings.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Tramadol Hydrochloride/ Acetaminophen | 0 | 76 | 0.0% |
| Gabapentin | 0 | 80 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Tramadol Hydrochloride/ Acetaminophen | 33 of 76 |
| Gabapentin | 18 of 80 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tramadol Hydrochloride/ Acetaminophen | Gabapentin |
|---|---|---|---|
| Dizziness | Nervous system disorders | 13 of 76 | 10 of 80 |
| Nausea | Gastrointestinal disorders | 14 of 76 | 4 of 80 |
| Somnolence | Nervous system disorders | 5 of 76 | 5 of 80 |
| Headache | Nervous system disorders | 6 of 76 | 4 of 80 |
| Dyspepsia | Gastrointestinal disorders | 6 of 76 | 3 of 80 |
The registry lists zero serious adverse events for tramadol hydrochloride/acetaminophen among 76 participants at risk and zero for gabapentin among 80 participants at risk. It also records other adverse events affecting 33 participants in the tramadol hydrochloride/acetaminophen group and 18 in the gabapentin group, using at-risk counts of 76 and 80, respectively. These are posted counts; no rates or comparative estimates are calculated.
In general, an adverse-event count describes how many participants were recorded with events under the registry’s reporting definitions. It does not show event timing, duration, recurrence, severity, or whether an event was judged related to treatment unless those details are separately reported. The registry record does not provide those details for the other adverse-event counts, nor does it report a statistical comparison of safety between groups.
The zero serious-event entries should be read as the recorded counts, not as proof that serious events are impossible or that the treatments have identical safety. The death entries are not reported in the registry record. The record also does not explain how the safety at-risk groups relate to the stated enrollment, so no reconciliation of those populations can be made from the reported information.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this completed Phase 4 study randomized participants with diabetic neuropathy to an open-label comparison of tramadol HCl/acetaminophen and gabapentin. It identifies change from baseline in pain intensity at Day 43 as the primary endpoint, describes the scale, and specifies an FAS with LOCF. These details let readers understand the intended question and some features of the analysis.
The primary efficacy findings themselves are not reported as a single comparison. The record does not give group means, standard deviations, a between-group estimate, a confidence interval, or a primary p-value. It also notes that the primary outcome involved several categories or time points and was not reduced to one comparison. The treatment contrast’s direction, magnitude, and precision therefore cannot be determined from the posted primary outcome information.
This absence does not mean the treatments had equal outcomes, nor does it mean either treatment performed better. It means the posted record lacks the result needed to quantify the comparison. A description of an endpoint or a study objective is not a result, and the fact that a trial was completed does not supply the missing outcome estimates.
The safety entries can be described narrowly: the registry records zero serious adverse events in each treatment group and other adverse events in both groups, with the reported counts and at-risk denominators. These figures do not by themselves establish a comparative safety effect. The registry does not report deaths, detailed event characteristics, or a statistical safety comparison.
Randomization can support causal interpretation when allocation, follow-up, outcome measurement, and analysis are adequately conducted. The record confirms random allocation but does not report enough detail to assess several of those aspects fully. Open-label status may matter for subjective pain reporting, and the stated LOCF method depends on assumptions about missing observations. The record does not provide the information needed to assess the effect of these limitations.
Accordingly, the appropriate reading is bounded: the registry describes the study design and outcome framework, and it records selected safety counts, but it does not provide the primary comparative efficacy result. No treatment recommendation or conclusion about relative effectiveness follows from these registry entries alone.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the difference between a registered research question and a reportable treatment estimate. The registry identifies randomization, the parallel-group design, the open-label status, the pain scale, the primary assessment time, and the intended analysis population. Those elements define much of the framework a reader would need to interpret a complete result.
The main statistical limitation is that no single primary comparison is reported. Without the group-level outcome summaries and an estimate of the contrast, the treatment effect cannot be quantified. Without a confidence interval, its precision cannot be assessed. The note that the primary outcome has several categories or time points and was not reduced to one comparison also makes the primary result difficult to identify. Statistical interpretation depends not only on naming an outcome but on reporting the analysis and its uncertainty.
The study also illustrates why design details and results need to be considered together. Randomization is intended to make a comparison less vulnerable to systematic differences at allocation, while open-label assessment can be relevant when the outcome is subjective. The FAS and LOCF description offers some information about analysis and missing-data handling, but the record does not state the extent of missingness or provide sensitivity analyses. These features shape interpretation without determining the direction of the result.
Finally, the safety counts should not be mistaken for a complete comparative safety analysis. Counts can be useful descriptive information, but event definitions, timing, severity, and statistical comparisons affect what can be inferred. Here, the record offers selected counts but does not report those supporting details.
The statistical lesson is that trial registration and design descriptions are not substitutes for complete outcome reporting. Readers need prespecified contrasts, numerical estimates, uncertainty intervals, analysis details, and transparent handling of missing data to judge the strength and limitations of a clinical comparison.
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.
Several trial-specific limitations constrain interpretation. The study was open-label, with masking listed as none. Because the primary outcome was participant-reported pain intensity, awareness of treatment assignment could have influenced expectations or reporting. The registry does not report any design feature intended to assess or mitigate that possibility.
The primary endpoint is described, but its group estimates and comparative result are not reported. The registry also flags that the primary outcome has several categories or time points and was not reduced to one comparison. This prevents a clear reading of the primary treatment contrast and its precision. The registry record does not report the analysis model, test, confidence interval, p-value, or covariate adjustment for the primary outcome.
The FAS definition excludes randomly assigned participants who did not meet the listed eligibility conditions or lacked a post-baseline efficacy assessment. LOCF was used, but the number of missing observations, reasons for missingness, and sensitivity analyses are not reported in the registry record. The assumptions behind carrying the last value forward therefore cannot be assessed.
The treatment schedules are incomplete in the registry descriptions, which are truncated before all dosing instructions are available. Adherence, treatment changes, discontinuations, and use of additional pain treatments are not reported. Participant characteristics and baseline comparability are also not described in the record.
Safety reporting is limited to serious-event counts and counts for other adverse events, with the recorded at-risk denominators. Event details and deaths are not reported in the registry record, and no comparative safety analysis is given. The registry also does not report a multiplicity strategy for the several listed outcomes or the trial’s own sample-size justification. Together, these gaps limit assessment of both the reliability and the scope of the trial findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Compare Safety and Efficacy of Tramadol Hydrochloride/Acetaminophen With Gabapentin in Participants With Diabetic Neuropathy — NCT00634543.
- Registry record last updated 2013-08-12; status last verified 2013-07.
- Results first posted 2013-07-16.
- 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.
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18. Record Summary
NCT00634543 is a completed Phase 4 randomized, open-label, parallel-group study sponsored by Janssen Korea, Ltd., Korea. It enrolled 162 participants and compared tramadol hydrochloride/acetaminophen with gabapentin for painful diabetic neuropathy. The primary endpoint was change from baseline in pain intensity score at Day 43, measured on an 11-point numerical rating scale. The FAS included eligible randomized participants with at least one post-baseline efficacy assessment, and LOCF was used.
The registry record does not report a single primary comparison or its numerical estimates. It lists zero serious adverse events in each group and other adverse-event counts of 33 and 18, respectively; deaths are not reported in the registry record. The study’s design and outcome definitions are available, but the posted information does not establish the comparative efficacy result or its precision.