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 Pharmacokinetic, Efficacy and Safety Study of Tapentadol Oral Solution in Children With Postoperative Pain (NCT01729728), a na phase 2 study. The primary outcome is Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01729728 |
| Phase | Phase 2 |
| Condition | Postoperative Pain, Acute Pain |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 86 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Grünenthal GmbH |
| Results posted | Yes |
2. Clinical Question
Population
Children and adolescents aged from 2 years to less than 18 years with postoperative pain were the intended population. The primary pharmacokinetic assessment was specified for adolescents aged 12 to less than 18 years. The registry reports enrollment of 86 participants, but does not give age-specific enrollment totals for all study outcomes.
Intervention
Participants received tapentadol oral solution. The primary pharmacokinetic endpoint concerned serum concentrations after a single dose. The registry describes the solution as still being tested and not yet registered.
Comparator
There was no comparator group. The study was open-label and single-group, and the allocation field is listed as not applicable. It therefore does not provide a like-for-like comparison with another treatment or with a control condition.
Primary question
The primary question was descriptive and pharmacokinetic: what mean serum tapentadol concentrations were measured in adolescents after a single oral dose, over a timeframe of up to 15 hours? The registry also lists safety and pain-intensity outcomes, but the primary endpoint was not a comparison of pain relief between treatment groups.
The stated study purpose was to examine tapentadol in children, including how much was present in blood after a single oral dose, alongside safety and efficacy. Pain intensity was assessed using different scales across age groups. These assessments addressed a different question from the primary pharmacokinetic endpoint: they recorded pain ratings, whereas the primary endpoint described measured serum concentrations. The registry record does not report the actual concentration values or pain-intensity results, so the questions can be described but their answers cannot be assessed in the registry record reported there.
3. Trial Design
This was a Phase 2, open-label, single-group study of tapentadol oral solution in children and adolescents with postoperative pain. The registry lists enrollment of 86 and the study status as completed. The listed start was 2012-11 and primary completion was 2014-02. No randomized allocation or masking is described; allocation is listed as not applicable and masking as none. Since there was no comparator group, the study design does not support a direct treatment-versus-control estimate.
The primary pharmacokinetic outcome was specified for adolescents aged 12 to less than 18 years, in the Pharmacokinetic Set. It concerned mean and standard deviation of serum tapentadol concentrations after a single dose, measured over a timeframe of up to 15 hours. The registry also lists pain-intensity assessments for several age bands, along with respiratory rate, oxygen saturation, and systolic and diastolic blood pressure assessments. It lists 54 outcome measures in total, but does not provide results for those measures in the registry record.
The study therefore combines pharmacokinetic measurement with safety and pain assessment, but its primary question is not an efficacy contrast. Without a control group, pain ratings during treatment cannot establish how those ratings would have differed under another treatment or no treatment. The registry record does not report the detailed protocol, the rationale for the enrollment target, or a statistical analysis plan. The sponsor is listed as Grünenthal GmbH.
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: Consent was obtained for 86 participants in the trial. 66 participants were allocated and received study drug (investigational medicinal product). Pharmacokinetic data was obtained for the planned 56 participants.
Overall Study
| Stage | Adolescents | Older Children | Young and Very Young Children |
|---|---|---|---|
| STARTED | 21 | 28 | 17 |
| COMPLETED | 20 | 22 | 16 |
| NOT COMPLETED | 1 | 6 | 1 |
Reasons for not completing this period:
| Reason | Adolescents | Older Children | Young and Very Young Children |
|---|---|---|---|
| Adverse Event | 0 | 6 | 0 |
| Protocol Violation | 1 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic 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.
Population: Number of participants that were dosed.
| Characteristic | Unit | Adolescents | Older Children | Young and Very Young Children | Total |
|---|---|---|---|---|---|
| Participants analysed | 21 | 28 | 17 | 66 | |
| Age, Continuous | years | 15.5 (SD 1.6) | 8.3 (SD 1.6) | 3.4 (SD 1.1) | 9.3 (SD 4.9) |
| Sex: Female, Male: Female | Participants | 9 | 17 | 8 | 34 |
| Sex: Female, Male: Male | Participants | 12 | 11 | 9 | 32 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 21 | 27 | 15 | 63 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 2 | 2 |
| Region of Enrollment: United States | participants | 21 | 28 | 17 | 66 |
| Weight | kilograms | 61.30 (SD 9.78) | 28.85 (SD 5.89) | 16.34 (SD 2.20) | 35.95 (SD 19.36) |
| Height | centimeter | 170.6 (SD 10.7) | 132.9 (SD 11.1) | 101.7 (SD 8.1) | 136.9 (SD 28.3) |
6. Primary Endpoint
The registry lists the primary outcome as Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years)., measured over up to 15 hours.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | nanogram per milliliter |
| Endpoint classification | Continuous Endpoint |
The primary endpoint concerns the serum concentration of tapentadol after a single oral dose in adolescents aged 12 to less than 18 years. Concentration is expressed in nanograms per milliliter, and the registry specifies the mean and standard deviation over a timeframe of up to 15 hours. Serum samples were analyzed using liquid chromatography coupled to tandem mass spectrometry. The stated lower limit of quantification was 0.2 ng/mL.
Pharmacokinetic measurements describe how much of a drug is present in the body over time. A concentration profile can help characterize exposure after dosing; it is distinct from a direct measure of pain relief and does not, by itself, establish a clinical benefit or harm. Reporting the mean gives a measure of the typical concentration at the relevant measurement points, while the standard deviation describes how dispersed individual measurements are around that mean. General statistical interpretation also depends on the number of observations contributing at each time point and on how values below the quantification limit are handled. Those details are not reported in the registry record.
The endpoint title and description identify the measure, age group, assay, and observation timeframe, but the actual concentration results are not reported in the registry record. Consequently, the concentration profile and its precision cannot be evaluated from these registry entries.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a completed, open-label study in which all participants received tapentadol oral solution, with no comparator group. Its primary endpoint was a pharmacokinetic description of serum concentrations in adolescents, not an estimate of the difference in pain outcomes between treatments. The registry entries reported in the registry identify the endpoint and its measurement approach, but do not include the concentration means or standard deviations. The primary result and its precision are therefore not reported in the registry record.
The listed enrollment of 86 is the overall study enrollment. It should not be treated as the number contributing to the primary pharmacokinetic endpoint: that endpoint is defined for the Pharmacokinetic Set and for adolescents, while the registry entries do not give the size of that set or its age-specific result counts. Nor does the total enrollment show how many participants contributed to each pain or safety assessment.
Pain-intensity outcomes were collected using age-specific scales, including the Visual Analog Scale, McGrath Color Analog Scale, Faces Pain Scale-Revised, and Face, Legs, Activity, Cry, Consolability Scale. A sum of pain-intensity differences over the four hours after dosing is also listed. The corresponding outcome estimates and their uncertainty are not reported in the registry record. In a single-group open-label study, such ratings can describe observations during the study, but they cannot separate treatment effects from other influences such as the course of postoperative pain, expectations, or other care.
For safety, the registry lists serious adverse events affecting 0 of 21 adolescents, 1 of 28 older children, and 0 of 17 young and very young children. It separately lists other adverse events affecting 12 of 21, 20 of 28, and 6 of 17, respectively. These are counts within age groups, not comparative estimates. The record does not provide a control group against which to interpret them. Death counts are not reported in the registry record.
Overall, the posted information establishes what outcomes were planned or listed and gives selected safety counts, but does not report the primary concentration values, pain results, or a comparative treatment effect. Conclusions about the size or precision of a pharmacokinetic or pain outcome cannot be drawn from the endpoint descriptions alone.
9. Statistical Methods Explained
For continuous outcomes, a mean describes the average of measured values, and a standard deviation describes how widely those values vary around the average. These summaries are useful for conveying the level and variability of a measurement, but they do not by themselves show how precisely the mean has been estimated. Precision is commonly described with a confidence interval. General explanation: a confidence interval expresses a range of values compatible with the data and the statistical method used; a narrower interval indicates greater precision, while a wider interval indicates more uncertainty. The registry entries do not report a confidence interval for the primary endpoint.
What does the pharmacokinetic summary describe?
The primary endpoint is the mean and standard deviation of serum tapentadol concentrations in adolescents after a single dose, with measurements over a timeframe of up to 15 hours. Concentration measurements at different times describe the observed profile across that timeframe. The registry specifies an assay using liquid chromatography coupled to tandem mass spectrometry and a lower limit of quantification of 0.2 ng/mL. The actual values at any measurement time are not reported in the registry record. The record also does not state the exact sampling times or how measurements below the assay’s quantification limit were handled.
General explanation: a lower limit of quantification is the lowest concentration that an assay can quantify reliably under its stated conditions. Values below that limit may require a prespecified analytic approach, and that approach can affect summaries. The handling method is not reported in the registry record, so no assumption about it is appropriate.
Why does the single-group design matter?
A single-group study can describe what was observed among participants who received the intervention. It does not directly estimate the difference between that group and a concurrent control group. General explanation: a treatment contrast requires outcomes under at least two comparison conditions; without such a comparison, observed changes can also reflect the natural course of the condition, expectations, measurement practices, or other care. This limitation applies to interpretation of the listed pain assessments as well as to any safety comparison. The study is open-label, so participants and study personnel were not masked to treatment according to the registry.
How should pain scales be understood?
The registry lists different pain-intensity scales for different age ranges: the Visual Analog Scale for adolescents, the McGrath Color Analog Scale for adolescents and older children, the Faces Pain Scale-Revised for children, and the Face, Legs, Activity, Cry, Consolability Scale for young and very young children. It also lists the sum of pain-intensity differences over the four hours after dosing, derived from the different scales and for all age groups. These measures are not the primary pharmacokinetic endpoint. Their results are not reported in the registry record, and the registry entries do not describe how measurements from different scales were combined or interpreted.
General explanation: an outcome measure should be interpreted in light of the scale’s range, direction, timing, and population. When different instruments are used across age groups, the meaning and comparability of scores depend on the instruments and analysis procedures. Those details are not reported in the registry record, so no score conversion or cross-age comparison can be inferred.
What do the planning assumptions mean?
The registry’s sample-size note describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. The note also distinguishes participants per arm for most outcomes from total events for time-to-event outcomes. These are planning assumptions, not a description of this trial’s single-group design. No resulting sample-size values or observed effect estimate are reported in the registry record. Such illustrations are not observed power and should not be interpreted as evidence about the trial’s ability to detect an effect.
General explanation: over-dispersion occurs when outcome variability is greater than a statistical model assumes. If present and unaccounted for, it can make uncertainty estimates too small. The registry entries do not identify a model for over-dispersed data, or any model used for the primary endpoint; this general point is not a claim that over-dispersion occurred in this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 54 outcome measures, spanning pharmacokinetic, pain, and safety assessments. It also lists pain scales for different age groups and several physiological measures. When many outcomes are examined, the chance of at least one apparently notable result can increase. General explanation: multiplicity procedures are methods for addressing the interpretation of multiple statistical tests, for example by adjusting significance thresholds or prioritizing a limited set of outcomes. Whether such procedures are needed and which method is suitable depend on the planned analyses and their purpose.
The registry entries do not report a multiplicity strategy, a hierarchy of secondary outcomes, or a detailed statistical analysis plan. The number of analyses is listed as zero. This does not establish that no analyses were conducted; it indicates that analyses are not reported in the registry record as. Results for the listed outcomes are also not reported in the registry record, so it is not possible to assess how many outcome comparisons were made or how multiplicity was handled.
The registry does not report how missing observations were handled, whether any participants were excluded from particular analyses, or the number contributing to each outcome. It identifies the primary analysis population as the Pharmacokinetic Set, but does not define that set or give its size. General explanation: missingness can affect an estimate when the participants with observed data differ systematically from those without observed data. The consequences depend on why values are missing and on the analysis method. Neither the pattern of missing data nor the handling method is reported in the registry record, so the direction or magnitude of any effect cannot be assessed.
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 |
|---|---|---|---|
| Adolescents | 0 | 21 | 0.0% |
| Older Children | 1 | 28 | 3.6% |
| Young and Very Young Children | 0 | 17 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3.6% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Adolescents | 12 of 21 |
| Older Children | 20 of 28 |
| Young and Very Young Children | 6 of 17 |
Most frequent serious adverse event terms
| Event term | Organ system | Adolescents | Older Children | Young and Very Young Children |
|---|---|---|---|---|
| post-procedural hemorrhage | Surgical and medical procedures | 0 of 21 | 1 of 28 | 0 of 17 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Adolescents | Older Children | Young and Very Young Children |
|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 6 of 21 | 9 of 28 | 1 of 17 |
| Vomiting | Gastrointestinal disorders | 3 of 21 | 8 of 28 | 0 of 17 |
| Dizziness | Nervous system disorders | 3 of 21 | 3 of 28 | 0 of 17 |
| Headache | Nervous system disorders | 2 of 21 | 0 of 28 | 2 of 17 |
| Cough | Respiratory, thoracic and mediastinal disorders | 0 of 21 | 0 of 28 | 2 of 17 |
| Pyrexia | General disorders | 1 of 21 | 1 of 28 | 0 of 17 |
| Somnolence | Nervous system disorders | 1 of 21 | 1 of 28 | 0 of 17 |
| Infusion site irritation | General disorders | 0 of 21 | 0 of 28 | 1 of 17 |
| Vessel puncture site bruise | General disorders | 0 of 21 | 0 of 28 | 1 of 17 |
| Cardiac murmur | Investigations | 0 of 21 | 0 of 28 | 1 of 17 |
Serious events with the highest arm-level rate: post-procedural hemorrhage (3.6%).
The registry lists serious adverse events separately from other adverse events for three age groups. Serious adverse events affected 0 of 21 adolescents, 1 of 28 older children, and 0 of 17 young and very young children. Other adverse events affected 12 of 21 adolescents, 20 of 28 older children, and 6 of 17 young and very young children. These counts describe participants in each group and should not be read as a comparison with an untreated or alternative-treatment group.
The registry also lists post-procedural hemorrhage as a top serious adverse event term at 3.6%. It does not specify in the registry record the age group associated with that term. Death counts are not reported in the registry record; a blank or null count should not be interpreted as a confirmed absence of deaths. The record does not provide event-level timing, duration, severity details beyond the serious-event categorization, or an explanation of the relationship of events to treatment. General explanation: adverse-event counts can describe what was observed, but a single-group record cannot determine how much risk is attributable to the intervention rather than the procedure, underlying condition, or other factors.
12. What the Result Does, and Does Not, Mean
This trial addresses a relevant statistical question: how serum tapentadol concentrations were characterized after a single oral dose in adolescents, alongside safety and pain assessments across pediatric age groups. Its open-label, single-group design is suited to describing observations among participants who received the solution, but it does not provide a concurrent control comparison. The registry identifies the primary endpoint, assay, measurement timeframe, and analysis population, but the concentration results themselves are not reported in the registry record.
The listed pain scales indicate that pain intensity was assessed using instruments selected for different age groups. The registry also identifies a four-hour sum of pain-intensity differences and physiological safety measures. However, their numerical results and uncertainty are not reported in the registry record. The endpoint list alone cannot establish the magnitude, precision, or comparative meaning of any pain changes.
Safety counts show that serious and other adverse events were recorded among participants in the listed age groups. Without a control group and additional details on events and their context, these counts cannot establish whether the intervention caused an event or how the observed counts compare with another care condition. They also do not substitute for the unreported concentration and pain results.
General explanation: evidence from a clinical study is interpreted in relation to its design, outcome definitions, analysis populations, and uncertainty. A descriptive result can inform understanding of observed measurements, while a causal or comparative claim requires a design and analysis that support that inference. For this study, the registry entries support describing the questions and methods recorded, plus the listed safety counts. They do not support a conclusion about the size or precision of the primary pharmacokinetic result, or a comparative conclusion about pain outcomes.
13. Why This Trial Matters Statistically
Statistically, this study is notable for separating a pharmacokinetic question from a treatment-effect comparison. Its primary endpoint was serum concentration after a single oral dose, summarized by mean and standard deviation in adolescents over a timeframe of up to 15 hours. This makes the endpoint a description of measured drug exposure, rather than a direct comparison of pain outcomes between treatment groups.
The pediatric age range also matters for measurement. The registry lists different pain instruments for adolescents, older children, children, and young or very young children. Different instruments may be appropriate to different developmental stages, but results require careful interpretation in light of their definitions and scoring. The actual pain results and the analytic approach to these measures are not reported in the registry record.
The single-group, open-label design clarifies the limits of what the data can establish. It can document observations among participants receiving tapentadol oral solution, but it cannot estimate a concurrent treatment contrast. This distinction helps prevent descriptive measures from being mistaken for controlled evidence of an effect. The registry’s planning note also illustrates why design assumptions must be kept separate from the completed study: its sample-size illustration assumes equal allocation between two arms, while this trial is listed as single-group. The resulting planning numbers are not reported in the registry record, and the note should not be read as a design description or as observed power.
Finally, the registry identifies safety counts but does not report the primary concentration values, detailed outcome results, or analysis methods. This illustrates a broader statistical point: knowing which outcomes were defined is not the same as having enough reported data to assess their magnitude and precision.
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 central limitation for interpreting the primary endpoint is that the registry record does not report the serum concentration values, standard deviations, or the number of participants contributing at each measurement time. It specifies the Pharmacokinetic Set but does not define that set or state its size. The timing of individual samples and the handling of measurements below the lower limit of quantification are also not reported in the registry record.
The study was open-label and single-group, with no comparator. Consequently, it cannot provide a direct controlled estimate of the effects of tapentadol relative to another treatment or a control condition. This is especially important for interpreting pain ratings, which may be affected by factors beyond treatment. Pain outcomes and their uncertainty are not reported in the registry entries.
The enrollment of 86 does not indicate how many participants contributed to each age-specific endpoint. Age-group sample counts are given for adverse-event reporting, but not for the primary pharmacokinetic or pain outcomes. The registry also lists 54 outcome measures without reporting a multiplicity approach, detailed statistical analysis plan, or missing-data method. The rationale for the enrollment target and any interim analyses are not reported in the registry record.
Safety information is limited to grouped counts, a listed serious-event term, and age-group denominators. Death counts are not reported in the registry record, and the registry entries do not provide event-level context or attribution. These limitations mean the posted information supports a description of the design and selected safety counts, but not a detailed appraisal of endpoint estimates, precision, or comparative effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetic, Efficacy and Safety Study of Tapentadol Oral Solution in Children With Postoperative Pain — NCT01729728.
- Registry record last updated 2019-11-04; status last verified 2019-10.
- Results first posted 2014-11-27.
- 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
The registry describes NCT01729728, a completed Phase 2, open-label, single-group study of tapentadol oral solution for postoperative pain in children and adolescents. Enrollment was 86. The primary endpoint was mean and standard deviation of serum tapentadol concentrations in adolescents aged 12 to less than 18 years after a single dose, measured over a timeframe of up to 15 hours using liquid chromatography coupled to tandem mass spectrometry. The stated lower limit of quantification was 0.2 ng/mL.
The record lists pain-intensity outcomes across age groups, physiological assessments, and 54 outcome measures. It provides grouped serious and other adverse-event counts, but the primary concentration results and pain results are not reported in the registry record. There was no comparator group, and the detailed analysis plan, missing-data methods, and multiplicity approach are not reported in the registry record.