Pharmacokinetic Study of a Fixed Dose Combination Nefopam Hydrochloride (30 mg) / Paracetamol (500 mg): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetic Study of a Fixed Dose Combination Nefopam Hydrochloride (30 mg) / Paracetamol (500 mg) (NCT05129137), a randomized phase 1 study. The primary outcome is Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose.

2. Clinical Question

3. Trial Design

This is a Phase 1, randomized, unmasked crossover study of oral single-dose treatments. The registry record lists 32 enrolled healthy volunteers and marks the study as completed. The start date is 2021-11-29, and the primary completion date is 2021-12-27. Unmasked means that masking is listed as none; the record does not describe any steps taken to conceal treatment assignment from participants or study personnel.

The treatment conditions were a fixed-dose combination of nefopam hydrochloride 30 mg and paracetamol 500 mg, nefopam hydrochloride 30 mg alone, paracetamol 500 mg alone, and the two individual components taken concomitantly. Each arm description specifies a single dose of 2 tablets. A crossover design means participants receive more than one treatment condition over the course of the study, rather than being assigned only one condition. Randomization can be used to determine the order in which treatments are received, but the treatment sequence is not reported in the registry record.

The crossover structure can allow comparisons within the same participant, which may help account for stable differences between participants. That general advantage depends on the study’s conduct and analysis. The registry record does not report the treatment sequence, washout interval, period structure, or a statistical model for accounting for within-participant and period effects. Those details should not be inferred from the design label alone.

The listed primary completion date and completed status describe study progress, not whether a particular pharmacokinetic comparison met a criterion. Results for the primary endpoint are not reported in the registry record. The stated goal is to assess pharmacokinetic profiles after a single dose; the record does not provide a sample-size justification or describe the decision process behind enrollment of 32 participants.

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.

First Period

Second Period

Reasons for not completing this period:

Third Period

Reasons for not completing this period:

Forth Period

Reasons for not completing this period:

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 Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose, measured over up to 48 hours post dose.

The primary endpoint is described as the pharmacokinetic profiles of nefopam and paracetamol after a single dose. The description specifies peak plasma concentration, Cmax, in ng/mL, with measurements at multiple timepoints through 48 hours post dose. Sampling is listed before administration, within 60 min, and at scheduled times after dosing. The measure is summarized as a mean with standard deviation.

Cmax is used in pharmacokinetic research to describe the highest measured plasma concentration following administration. In general, concentration measurements over time help characterize how a drug appears in plasma and how its profile evolves after a dose. Cmax focuses on the peak rather than describing the entire concentration-time curve. It does not, by itself, describe the time at which the peak occurs or the total exposure over the observation period.

The endpoint description refers to profiles in each treatment arm, but the registry record does not give the numerical means, standard deviations, or treatment comparisons. It also does not clarify whether a separate Cmax was derived for each participant from the concentration-time measurements or how any such derivation was handled. The listed outcome is pharmacokinetic, not a measure of symptom relief or another clinical outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a crossover design mean?

In general, a crossover study exposes participants to multiple treatment conditions in sequence. Because a participant may contribute observations under more than one condition, comparisons can use within-participant information. This can reduce the influence of stable differences between participants, such as differences that persist across treatment periods. The benefit is not automatic: the analysis needs to reflect the repeated measurements and the study’s period structure.

The registry record labels this study randomized and crossover, but does not report the treatment sequence, the number or timing of periods, or a washout interval. A washout is an interval intended to reduce the influence of an earlier treatment on measurements in a later period. Whether it was needed, how long it was, and how carryover was assessed are not reported in the registry record. The statistical model and its handling of treatment, period, sequence, and participant effects are also not reported in the registry record.

What does randomization contribute?

In general, randomization assigns treatment order using a chance process. In a crossover study, this can help prevent treatment sequence from being systematically associated with participant characteristics. Randomization does not itself guarantee that all sources of bias are absent, nor does it disclose the sequence used. The registry record identifies randomized allocation but does not report the allocation procedure, sequence generation, or concealment details.

How should Cmax and concentration profiles be understood?

Pharmacokinetic studies measure drug concentrations over time after administration. The primary outcome description names Cmax, or peak plasma concentration, in ng/mL, and gives a sampling schedule that extends up to 48 hours post dose. In general, the concentration-time profile describes the pattern of measured concentrations across the observation period; Cmax condenses that information to the peak concentration. The peak can be useful for comparing concentration levels, but it does not describe every aspect of exposure.

In general, a concentration profile may also be characterized using measures such as the time to peak or the area under a concentration-time curve. Those measures are not named as the primary endpoint in the record, so their values should not be assumed. The record gives no numerical Cmax values, no standard deviations, and no concentration-time estimates. It also does not describe the laboratory assay, sample handling, or method used to derive a participant-level peak from scheduled samples.

What do mean and standard deviation tell the reader?

The endpoint is specified as a mean and standard deviation. In general, the mean is a measure of the center of the observed values. The standard deviation describes their spread around the mean. They answer different questions: a mean gives a central summary, while a standard deviation conveys how variable individual values are. A standard deviation is not a confidence interval and does not directly indicate the precision of a treatment comparison.

For a comparison, a confidence interval would generally help show the range of values compatible with the data and the analysis assumptions. A p-value, when reported, addresses a different question concerning compatibility with a specified null hypothesis. Neither is reported for the primary outcome in the registry record. No statistical analysis is listed, so the data cannot be interpreted as evidence for or against a particular treatment contrast using inferential statistics.

Why do analysis details matter?

Repeated concentrations within a participant are generally correlated rather than independent. In a crossover study, observations from different treatment periods within the same participant are also related. General statistical methods account for these dependencies; treating related observations as independent can misstate uncertainty. The appropriate method depends on the design and endpoint, and cannot be identified from the word “crossover” alone.

The record specifies mean and standard deviation, but does not state whether the primary analysis compared treatment means, modeled the concentration-time observations, or used another approach. It does not report covariate adjustment, handling of missing concentrations, or assumptions about the distribution of the outcome. Pharmacokinetic data may have skewed distributions or other features that affect the choice of summary and model; whether such features were examined is not reported in the registry record.

What can be inferred from the sample-size information?

The registry record does not report a sample-size justification or describe a target power for the original trial. Any sample-size illustration based on an observed effect is a planning calculation, not observed power and not evidence that the study was designed around that effect. The assumptions described for such illustrations include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a fraction of the observed effect. Numerical planning results are not reported in the registry record. They should not be confused with the enrolled sample of 32 participants or with an analysis of the trial’s actual precision.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description includes concentration profiles for two components and multiple sampling times, while the study compares four treatment conditions. This creates several possible ways to summarize or compare the data. In general, testing many outcomes or timepoints can increase the chance of obtaining an apparently notable result by chance if no adjustment or prespecified hierarchy is used. The registry record does not report a multiplicity strategy, a hierarchy of comparisons, or which treatment contrast was designated for formal inference.

The registry record lists seven outcome measures, including metabolite profiles and treatment-emergent adverse events, but lists zero analyses. It does not state whether the primary Cmax comparisons were planned separately by component, whether timepoint-specific tests were intended, or whether any correction for multiple testing was planned. These details are not reported in the registry record.

Missing-data handling is also not described. The record does not report whether any concentration samples were missing, how incomplete profiles were handled, or whether exclusions occurred. It does not describe the analysis population, such as whether the primary analysis included all randomized participants or a subset with evaluable pharmacokinetic samples. These details matter because exclusions or incomplete measurements can affect both the estimated treatment summaries and their uncertainty.

In general, a complete interpretation would distinguish the enrolled population from the participants included in each analysis and describe reasons for missing measurements. That information is not reported in the registry record. Without the analysis population, missing-data methods, and multiplicity plan, the precision and confirmatory status of any potential comparison cannot be assessed. No unreported method should be inferred from the crossover design or the endpoint description.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record lists serious adverse events separately from other adverse events for each treatment group. For the fixed-dose combination group, 32 were at risk, 0 serious adverse events were recorded, and 1 other adverse event was recorded; deaths were 0. For nefopam hydrochloride alone, the corresponding counts were 32 at risk, 0 serious adverse events, 1 other adverse event, and 0 deaths. For paracetamol alone, they were 32 at risk, 0 serious adverse events, 0 other adverse events, and 0 deaths. For nefopam hydrochloride and paracetamol taken together, they were 32 at risk, 0 serious adverse events, 1 other adverse event, and 0 deaths.

These are counts for the listed treatment groups. They do not establish that participants had no symptoms or events beyond those captured in the registry record, and the record does not provide event descriptions for the other adverse events. No serious adverse event terms are listed. Because the study is crossover, the same participant may contribute to more than one treatment group; the group counts should not be added to infer a count of distinct participants with events. The registry record does not provide further detail on event timing, attribution, severity classification for other events, or the safety analysis population.

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

The study addresses a pharmacokinetic question: how plasma concentrations of nefopam and paracetamol are profiled after a single dose of the fixed-dose combination, the individual components, or the components taken concomitantly. The randomized crossover design is suited to comparisons in which participants receive multiple conditions, and the endpoint description specifies Cmax and measurements through 48 hours post dose.

The registry record does not report numerical primary outcome results or statistical analyses. It therefore cannot establish the observed mean peak concentrations, the variability of those measurements, or the size and precision of any differences among treatment conditions. A design description is not an outcome finding. The absence of posted estimates also means the record cannot support a conclusion about whether the concentration profiles were similar or different.

Even if concentration results were available, pharmacokinetic findings would answer a different question from whether a treatment improves a clinical outcome. Concentrations and Cmax describe drug levels in plasma; they do not by themselves establish symptom effects, clinical benefit, or an overall balance of benefits and harms. No such clinical outcome is identified as the primary endpoint in the record.

The safety counts show no serious adverse events in the listed groups and report a small number of other events. These counts are descriptive, and the record does not give the event details or an inferential comparison. They should not be used to claim that the treatments are equivalent in safety. The study’s status as completed likewise does not indicate what its results were.

The most defensible reading is limited to what is documented: a completed Phase 1 randomized, unmasked crossover study in healthy volunteers, with four single-dose treatment conditions and a pharmacokinetic primary outcome. The registry record does not report the primary results, analysis methods, or missing-data handling needed for a fuller statistical interpretation.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its design and outcome raise questions about within-participant comparisons, repeated measurements, and the definition of a treatment contrast. In a crossover study, each participant can contribute observations under multiple treatment conditions. In general, analyzing those observations as related can improve efficiency compared with ignoring participant-level pairing, but the analysis must also account for treatment order and period structure where relevant.

The concentration outcome is measured across a sequence of timepoints, while the primary description names Cmax. Those are related but not interchangeable summaries: a concentration-time profile retains information across sampling times, whereas Cmax focuses on the peak. A clear analysis plan would identify how peak values are derived and which contrast is primary. Those methods are not reported in the registry record.

The four conditions also distinguish the fixed-dose combination from each component alone and from concomitant administration of the individual components. Such comparisons can be important when assessing whether a combined formulation has a concentration profile that differs from the individual or co-administered components. The registry record does not report the numerical estimates needed to make those comparisons.

Finally, the primary outcome includes multiple components and timepoints, and the registry lists additional outcomes. In general, prespecifying a primary comparison and explaining multiplicity handling helps readers distinguish planned inference from exploratory examination. The record does not report those details or any primary analysis results. This makes the study’s design understandable at a high level, while leaving its statistical findings and precision unknown.

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 most important limitation for interpretation is that the registry record does not report numerical results for the primary pharmacokinetic outcome. Means, standard deviations, treatment contrasts, confidence intervals, and p-values are not available in the record. It lists zero analyses, and the primary outcome has several categories or timepoints rather than a single reported comparison. Consequently, the effect size and precision cannot be evaluated.

The record describes the study as randomized and crossover but does not report treatment sequence, period structure, or washout interval. It does not describe how the analysis handled repeated measures, treatment order, potential carryover, or participant-level correlation. These omissions prevent an assessment of whether the statistical methods corresponded to the design.

The registry record does not report a sample-size justification, so the rationale for enrollment of 32 participants cannot be evaluated. It also does not report an analysis population, the number of participants with evaluable pharmacokinetic measurements, missing-data frequency, or methods for handling incomplete profiles. The impact of missing or excluded observations is therefore unknown.

The outcome description emphasizes Cmax and provides a sampling schedule through 48 hours, but does not state how Cmax was derived from measured concentrations or report other pharmacokinetic summaries. Further, the study enrolled healthy volunteers and used single-dose conditions; the record does not establish how these results would relate to other populations, dosing patterns, or clinical outcomes. The safety record contains limited event detail, with no descriptions of the other adverse events. These limitations arise from what the registry record reports and should not be filled in by assumption.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetic Study of a Fixed Dose Combination Nefopam Hydrochloride (30 mg) / Paracetamol (500 mg) — NCT05129137.
• Registry record last updated 2024-10-31; status last verified 2024-10.
• Results first posted 2024-10-31.
• 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

NCT05129137 is a completed Phase 1 randomized, unmasked crossover study sponsored by Unither Pharmaceuticals, France. The record lists 32 healthy volunteers and compares a fixed-dose combination of nefopam hydrochloride 30 mg and paracetamol 500 mg with the individual components and the components taken concomitantly. Each arm description specifies a single dose of 2 tablets.

The primary outcome is described as nefopam and paracetamol pharmacokinetic profiles, including Cmax in ng/mL, with sampling through 48 hours post dose and summaries specified as means and standard deviations. Primary outcome values and statistical analyses are not reported in the registry record. Serious adverse event counts are 0 in each listed group; other adverse event counts are 1, 1, 0, and 1, respectively, and deaths are 0 in each group.