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 Nicotine Pharmacokinetics of THS Single Use of a Regular or a Menthol Stick Compared to CIG (NCT05789420), a randomized na study. The primary outcome is Maximum Plasma Concentration [Cmax].
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05789420 |
| Phase | NA |
| Condition | Smoking, Tobacco |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 31 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Philip Morris Products S.A. |
| Results posted | Yes |
2. Clinical Question
Population
The study involved healthy adult subjects who smoked, according to the official study title. The registry lists an enrollment of 31. The primary endpoint analysis excluded some participants because of protocol deviations, including missing measurements; the number retained for that analysis is reported separately for each product group.
Intervention
The study evaluated single use of a Tobacco Heating System (THS) with either a regular stick, identified as P1R, or a menthol stick, identified as P1M. The registry describes the THS as using induction heating technology.
Comparator
The comparator was smoking a single combustible cigarette, identified as CIG. Product-use order was randomized, and the study used a crossover design.
Primary question
The primary question was how the maximum plasma nicotine concentration, or Cmax, after single use of each THS stick compared with Cmax after smoking a single cigarette. Cmax was measured from the start of product use to 24 hours. The study also evaluated subjective effects and assessed safety, but the primary endpoint was a pharmacokinetic measure.
This is a question about nicotine concentration over a defined observation period, not about long-term exposure, smoking behavior, or clinical outcomes. The registry’s stated purpose was to describe nicotine pharmacokinetic profiles during and after single use and to evaluate subjective effects related to product acceptance and likelihood of using THS again. The posted primary results give group-level geometric means and confidence intervals. They do not report a direct statistical test of either THS product against CIG, and the registry record does not report a primary endpoint comparison estimate.
3. Trial Design
The registry describes a randomized, controlled, open-label, single-center crossover study. Participants used products in randomized product-use sequences. The products were a THS regular stick, a THS menthol stick, and a combustible cigarette. The study was classified as phase NA. Its status is completed.
The product sequence descriptions refer to abstinence from any tobacco or nicotine product for at least 23 hours on Day 1, and to at least 23 hours since previous investigational product use on Day 2 and Day 3 as a nicotine wash-out. The descriptions say that participants then smoked a single cigarette or used THS once, according to randomized sequence. The registry record does not give further detail about the conduct of each period or how the wash-out interval was verified.
The registry lists enrollment as 31. For the primary endpoint, the posted analysis groups each have n=30. The endpoint population description notes that some participants were excluded for protocol deviations, including missing measurements. The record does not explain the specific deviations for each participant or provide a complete flow from enrollment to analysis.
The study dates in the record are 2023-02-16 for start and 2023-04-02 for primary completion. The sponsor is Philip Morris Products S.A. These details describe the registry entry and do not establish whether all planned procedures were completed as intended. Further information about allocation procedures, sequence balance, concealment, or the rationale for the enrollment target is not reported in the registry record.
A crossover design compares product-use periods within the same participants, which can reduce the influence of stable differences between people when the analysis accounts for the repeated measurements appropriately. That is a general statistical feature of crossover studies, not a claim about the unreported analysis used for this trial. The registry record does not describe an analytical model that accounts for sequence, period, or within-participant correlation.
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: 32 subjects were screened for the study who gave informed consent and had at least one safety assessment, which were the criteria for inclusion in the Safety Population. 31 subjects were enrolled (one subject completed alternate status but was not needed for study participation due to closed enrollment). One of the enrolled subjects was discontinued due to positive alcohol breath and urine tests on Day -1. A total of 30 subjects were randomized to participate in the study.
Screening and Safety Assessments
| Stage | Safety Population |
|---|---|
| STARTED | 32 |
| COMPLETED | 31 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Safety Population |
|---|---|
| Completed Alternate Status | 1 |
Enrollment
| Stage | Safety Population |
|---|---|
| STARTED | 31 |
| COMPLETED | 31 |
| NOT COMPLETED | 0 |
Randomization to Product Assessments
| Stage | Safety Population |
|---|---|
| STARTED | 31 |
| P1R Stick | 30 |
| P1M Stick | 30 |
| CIG | 30 |
| COMPLETED | 30 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Safety Population |
|---|---|
| Failed alcohol breath test and urine test on day -1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).
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: The safety population.
| Characteristic | Unit | Safety Population |
|---|---|---|
| Participants analysed | 32 | |
| Age, Continuous | years | 39.6 (SD 10.40) |
| Sex: Female, Male: Female | Participants | 17 |
| Sex: Female, Male: Male | Participants | 15 |
| Race/Ethnicity, Customized: White | Participants | 32 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | 32 |
| Body Mass Index | kg/m² | 26.037 (SD 2.8629) |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Plasma Concentration [Cmax], measured over Measured from start of product use to 24 hours.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | ng/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is maximum plasma concentration, Cmax, measured in ng/mL from the start of product use to 24 hours. It represents the highest plasma nicotine concentration recorded over that measurement interval after a single product use. The registry reports the endpoint as a geometric mean with a 95% confidence interval for each product group.
Cmax is used in pharmacokinetic studies because it describes the peak concentration observed after exposure. It complements measures that describe other features of a concentration-time profile, such as the timing of the peak or total exposure over time. Those additional measures are not the primary endpoint reported in this record.
As a general statistical point, a geometric mean is suited to data analyzed on a multiplicative scale and can summarize concentrations when their distribution is skewed. Its interpretation differs from an arithmetic average: it is based on the logarithmic scale and is transformed back to the original scale. The registry does not report the individual concentration measurements or the distributional diagnostics behind this choice.
A Cmax estimate is a measure of concentration, not a direct measure of subjective experience, product acceptance, safety, or long-term health effect. The registry separately states that subjective effects and safety were evaluated, but it does not post secondary outcome results in this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted geometric mean Cmax is 8.425 ng/mL for P1R, the THS regular stick, with a 95% confidence interval from 6.582 to 10.78. For P1M, the THS menthol stick, it is 7.475 ng/mL, with a 95% confidence interval from 5.464 to 10.23. For CIG, the combustible cigarette, it is 13.43 ng/mL, with a 95% confidence interval from 10.29 to 17.53. Each listed product group has n=30.
These are separate group estimates, not estimates of the difference between products. A confidence interval describes uncertainty around an estimated group quantity under the analysis assumptions; it is not a range containing a specified proportion of individual participants’ measurements. The intervals show that each group estimate is imprecise to some degree. Their widths reflect uncertainty, but the registry does not provide the underlying observations or enough methodological detail to assess how the intervals were constructed.
The numerical estimates place the reported CIG geometric mean above the reported means for both THS products. This descriptive ordering alone does not establish the size or statistical uncertainty of a product-to-product contrast. In particular, no direct contrast estimate, confidence interval for a contrast, or p-value is posted for the primary endpoint. The registry record also does not report whether the analysis used the paired structure expected in a crossover trial. Because of that, the group-level confidence intervals should not be treated as a substitute for a within-participant comparison.
The primary endpoint population excluded some participants for protocol deviations, including missing measurements. The registry does not report the detailed reasons or the effect of those exclusions on the estimates. The posted group sizes describe the endpoint analyses, while the enrollment entry describes the trial as a whole; the record does not provide a fuller accounting that reconciles them.
The study’s stated purpose was to describe nicotine pharmacokinetics after single use. The results therefore speak to measured Cmax in this study setting and population. They do not establish how repeated use would affect exposure, how concentrations relate to subjective effects, or whether any product has a favorable clinical or safety profile. Those broader conclusions are not supported by the primary endpoint estimates alone.
9. Statistical Methods Explained
The primary result is presented as a geometric mean and 95% confidence interval for each product. This is a summary of the concentration measurements within each product group. It is not, by itself, a statistical comparison between products. The registry record does not post a model, an estimated difference or ratio between products, or a test of a primary contrast.
What does a geometric mean describe?
In general, a geometric mean is calculated by transforming observations to a logarithmic scale, averaging on that scale, and transforming the result back. This approach is often used for concentration data because values may be right-skewed and relative changes may be more meaningful than equal absolute changes. The reported estimates remain on the original ng/mL scale. The specific transformation and analysis implementation for this trial are not reported in the registry record.
The geometric means should not be read as arithmetic averages or as values that every participant experienced. Individual measurements can vary around a group summary. The registry record does not provide participant-level values, a standard deviation, or another measure of individual variability for the primary endpoint.
How should the confidence intervals be read?
In general, a confidence interval communicates sampling uncertainty for an estimate under the method’s assumptions. A 95% confidence interval is produced by a procedure that, in repeated use under those assumptions, would cover the target quantity at the stated rate. It is not a statement that 95% of individual observations lie between the endpoints, nor does it assign a probability to the fixed true value after the interval has been calculated.
The posted intervals are for the group geometric means. They do not directly express uncertainty for the difference or ratio between two products. In a crossover study, the uncertainty of a contrast can depend on how each participant’s results across product periods are related. That within-participant information cannot be recovered from the separate group summaries. General statistical practice would estimate the prespecified contrast using a method that reflects the design; the method used is not reported in the registry record.
Why does the crossover structure matter?
Generally, crossover designs expose participants to more than one study condition and compare outcomes across periods. Because the same person contributes observations under different conditions, a suitable analysis can account for within-person correlation. This can improve precision compared with treating every observation as independent, but only when the design and data support the assumptions and the analysis handles relevant period and sequence effects.
The registry identifies this study as a crossover and describes randomized product-use sequences. It does not report the statistical model, whether period or sequence effects were included, or how within-participant correlation was handled. It also does not report tests for carryover or a rationale for the wash-out duration. No conclusion about these analytical choices can be drawn from the group summaries alone.
What can be concluded from the posted estimates?
The group estimates describe the observed primary endpoint summaries in the analysis populations recorded for P1R, P1M, and CIG. A descriptive comparison can note their ordering, but it cannot supply an inferential comparison that the registry does not post. Non-overlap or overlap of separate confidence intervals is not a replacement for a direct contrast analysis, particularly in a crossover design where paired observations matter.
The record lists 0 posted analyses. It therefore does not provide the planned or performed model details, hypothesis tests, adjustment procedures, or analysis diagnostics for the primary endpoint. Further statistical analysis details are not reported in the registry record. The absence of these details limits assessment of how the estimates were derived and how they should be interpreted beyond their descriptive role.
What do sample-size calculations mean?
In general, a sample-size calculation is a planning exercise based on assumptions about an effect to detect, variability, significance level, allocation, and analysis method. A planning illustration based on an observed effect is not an observed measure of power and does not show that the trial had adequate precision for a clinical decision. The registry record describes planning assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect framed as a stated fraction of the observed effect. The specific planning results are not reported in the registry record. The record also states that the listed analysis type was not reduced to one comparison, and that values were missing or not estimable for a two-arm comparison for another endpoint.
For this primary endpoint, no direct two-product contrast is posted. No new contrast can be derived reliably from the separate group summaries, especially without the paired participant-level data or the crossover analysis method. Thus, the posted Cmax results support descriptive reading of product-specific estimates and their confidence intervals, not reconstruction of an unreported inferential test.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 0 posted analyses and 0 posted secondary outcomes. Although the study description says subjective effects were evaluated, the registry record does not report secondary outcome results. It does not report a multiplicity strategy, such as a hierarchy of hypotheses or an adjustment across multiple tests. Without a set of posted tests and their prespecified relationships, the family of comparisons and any control of false-positive risk cannot be assessed.
The primary endpoint population description says some participants were excluded from analysis for protocol deviations, including missing measurements. The posted Cmax results list n=30 for each product group, while the enrollment entry is 31. The record does not give participant-level disposition, detail the exclusions by product period, describe a missing-data method, or state whether any imputation was performed. The reason for each missing measurement and whether missingness could be related to the outcome are not reported in the registry record.
Excluding observations can affect both the composition of the analysis population and the precision of estimates. In general, a complete-case analysis may be biased if the availability of measurements is related to participant characteristics or outcomes; methods for handling missing data depend on why values are missing and on the analysis objective. These are general considerations, not claims about the method used in this trial. The registry does not identify an intention-to-treat, per-protocol, or other named primary analysis population beyond noting exclusions for protocol deviations.
The record does not report whether interim analyses occurred or whether the statistical plan was amended. It also does not explain how protocol deviations were classified. Those items are not reported in the registry record, so the consequences for multiplicity and analysis-population selection cannot be evaluated from the posted entry.
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 |
|---|---|---|---|
| Safety Population | 0 | 32 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Safety Population | 0 of 32 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Safety Population | 0 of 32 |
The registry lists a Safety Population with 32 participants at risk for serious adverse events and 0 affected by serious adverse events. It reports 0 deaths. For other adverse events, it also lists 32 at risk and 0 affected. No top serious adverse-event terms are listed.
These figures are counts in the safety population as represented in the registry. They are not a comparison between the THS products and CIG, and the record does not provide separate adverse-event counts by product or sequence. The safety population count does not match the enrollment entry of 31; the registry record does not explain that difference, so it should not be reconciled by inference.
In general, observing no reported events in a study does not establish that an event cannot occur or that risk is absent. The interpretation depends on the population observed, duration of follow-up, event definitions, and completeness of reporting. The record does not provide detailed safety follow-up duration or event-collection procedures. The study description says safety was assessed throughout the study, but the posted figures alone do not support broader claims about safety beyond this recorded experience.
12. What the Result Does, and Does Not, Mean
The result describes the geometric mean maximum plasma nicotine concentration after single use of each product in the endpoint populations. The posted estimate for CIG is 13.43 ng/mL, compared with 8.425 ng/mL for the THS regular stick and 7.475 ng/mL for the THS menthol stick. The respective 95% confidence intervals communicate uncertainty around each group estimate. These summaries provide a pharmacokinetic description for the products and observation period studied.
The result does not, on its own, establish a statistically significant difference between products. The registry does not post a direct contrast, a confidence interval for a contrast, or a p-value. Separate group confidence intervals do not supply the missing paired comparison for a crossover design. Any conclusion about the magnitude or precision of a product contrast would require an appropriate analysis that is not reported in the registry record.
Nor does Cmax alone represent total nicotine exposure, subjective effects, product acceptance, likelihood of future use, or safety. The registry describes evaluation of subjective effects and safety, but does not post secondary outcome results. A single-use measurement cannot be assumed to describe repeated use or longer-term patterns.
The findings are specific to the study’s healthy adult subjects who smoked, its single-center setting, the products evaluated, and the stated observation window from product use to 24 hours. The registry record does not give enough detail to assess how representative the participants were of other populations or how the estimates would generalize beyond this setting. These limits distinguish a descriptive pharmacokinetic result from a broader claim about clinical outcomes or use in other circumstances.
13. Why This Trial Matters Statistically
This trial is statistically informative because it makes clear the difference between a set of product-specific estimates and an actual comparative analysis. The posted geometric means and confidence intervals summarize Cmax for the regular THS stick, menthol THS stick, and cigarette. They do not answer, with a direct inferential estimate, how much the products differ or how precise that difference is.
The crossover design is also important to interpretation. In general, a within-participant comparison can use information about how measurements from the same person relate across product periods. That structure may affect the standard error of a contrast and therefore its confidence interval. The registry identifies the crossover design but does not report whether the primary analysis used the paired structure or addressed period and sequence effects. The descriptive summaries cannot reveal those choices.
The record also illustrates why analysis-population details matter. Some participants were excluded from the primary endpoint analysis for protocol deviations, including missing measurements, while the reported endpoint group sizes and the overall enrollment entry describe different aspects of the study. Without participant flow and missing-data methods, readers cannot fully assess how exclusions may affect precision or representativeness.
Finally, the presence of a primary pharmacokinetic endpoint should not be confused with evidence about every outcome the study intended to explore. The study description mentions subjective effects and safety, but secondary results are not posted. Keeping those distinctions explicit prevents a concentration summary from being interpreted as a complete account of product acceptance, safety, or clinical effect.
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 registry record provides limited detail for independently assessing the primary analysis. It reports group geometric means and 95% confidence intervals but does not report the statistical model, a direct product contrast, a p-value, or the method used to account for the crossover structure. It is therefore not possible to evaluate the precision of a paired comparison from the posted summaries alone.
The primary endpoint population excluded some participants for protocol deviations, including missing measurements. The record does not specify the deviations, identify which product periods were affected, give a participant-flow account, or describe missing-data handling. Those omissions make it difficult to assess potential selection effects and the robustness of the estimates to missing measurements.
The single-center study involved healthy adult subjects who smoked and evaluated single product use. The findings may not describe other populations, settings, products, or patterns of use. The registry does not provide further demographic detail in this entry, so the representativeness of the analyzed participants cannot be assessed from the record.
The registry’s study description includes subjective effects and safety assessment, but no secondary outcome results are posted. The safety figures are not broken down by product, and the record does not give detailed event definitions or follow-up procedures. The record also does not report a multiplicity plan, protocol amendments, or interim analyses. These are specific limits on interpretation of this registry entry, not evidence that such procedures were or were not undertaken outside what is recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Nicotine Pharmacokinetics of THS Single Use of a Regular or a Menthol Stick Compared to CIG — NCT05789420.
- Registry record last updated 2024-11-22; status last verified 2024-09.
- Results first posted 2024-11-22.
- 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
NCT05789420 is a completed, randomized, controlled, open-label, single-center crossover study of single use of THS with a regular or menthol stick compared with smoking a single combustible cigarette. The registry lists enrollment of 31 and describes healthy adult subjects who smoked.
The primary endpoint was maximum plasma nicotine concentration, measured from product-use start to 24 hours and reported as a geometric mean with a 95% confidence interval. The posted group estimates are 8.425 ng/mL for P1R, 7.475 ng/mL for P1M, and 13.43 ng/mL for CIG. Each endpoint group lists n=30.
The registry record does not post a direct primary contrast, a statistical analysis model, or secondary outcome results. It notes exclusions for protocol deviations, including missing measurements. Safety results list 0 serious adverse events, 0 other adverse events, and 0 deaths among the reported safety population. Those registry figures describe the recorded study results and do not support broader conclusions beyond the stated study setting and outcomes.