A Relative Bioavailability Study of Nicotine Delivery From Selected Oral Nicotine Products: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Relative Bioavailability Study of Nicotine Delivery From Selected Oral Nicotine Products (NCT05452278), a randomized na study. The primary outcome is Nicotine Cmax.

2. Clinical Question

This is a relative bioavailability question: the focus is how nicotine exposure measured in blood differs across the selected products under the study conditions. The primary endpoint is maximum observed plasma nicotine concentration, or Cmax. Its value is the highest concentration recorded among the scheduled blood measurements for a product-use period.

The crossover arrangement means participants were assigned to product sequences rather than to a single product for the entire study. Each listed sequence includes all four products, with the order varied. That arrangement allows the study to collect measurements after each product within the same overall study. However, the registry record does not report a statistical model that accounts for the repeated measurements or sequence structure.

The registry record describes healthy volunteers who used snus or nicotine pouches. It does not report further eligibility details, such as age criteria or the amount or duration of prior product use. The clinical question is therefore limited to the study population and conditions described in the record; it should not be extended automatically to other populations or settings.

3. Trial Design

The registry describes a randomized crossover study of Product A, Product B, Product C, and Product D, with an enrollment of 27. The brief summary calls the study single-blind, while the registry masking field says none. The record therefore contains differing descriptions of blinding, and does not explain the discrepancy. The study is listed as completed and as involving healthy volunteers.

Participants followed one of four product sequences: ABCD, BCDA, CDAB, or DABC. In each sequence, a different product was used on each day of the four-day confinement period. The study summary describes a screening visit and a clinic confinement visit, followed by a telephone call within a week of last product use. The record does not state how participants were assigned among sequences or whether sequence allocation was balanced.

The primary outcome is a continuous pharmacokinetic measure: maximum observed plasma nicotine concentration, reported in ng/mL as a mean and standard deviation for each product. Blood measurements were scheduled before product use and at multiple times extending through 8 hours after product use began. The primary analysis population is described as participants who used a particular product. Product-specific analysis counts are reported, and the registry cautions that these can differ from the number in the participant-flow arms.

The registry also lists percentage of orally extracted nicotine and urge-to-use Emax as secondary outcomes. The record does not report a statistical analysis plan, a sample-size justification for the original study, or details of how period, sequence, or within-participant correlation were handled. The planning illustrations associated with the posted comparisons are separate from the original study design assumptions.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The analysis population represents all subjects who used a specific product. The overall number of participants analyzed for each product is therefore different from the number of participants in each arm provided in the Participant Flow module.

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 Nicotine Cmax, measured over 5 minutes prior to product use and 5, 10, 15, 20, 25, 30, 45, 60, 90 minutes, 2, 4, 6 and 8 hours post start of product use.

The primary endpoint is maximum observed plasma nicotine concentration, or Cmax, measured in ng/mL. It represents the highest recorded plasma nicotine concentration among the scheduled blood samples for a product-use period. The registry specifies measurements 5 minutes prior to product use and at 5, 10, 15, 20, 25, 30, 45, 60, and 90 minutes, and 2, 4, 6, and 8 hours after product use began.

Cmax is used in pharmacokinetic comparisons because it describes the observed peak concentration following product use. In a relative bioavailability study, comparing this peak across products can help characterize differences in nicotine exposure under the study conditions. It does not, by itself, describe the full concentration-time profile, total exposure, or the timing of the peak. Those questions require other measures or analyses, and the registry record does not post a primary outcome for total exposure.

The posted product-level results report means and standard deviations. These summaries describe the observed Cmax values within each product analysis group, while the unadjusted comparisons express differences in means relative to Product A. A mean captures the group average; the standard deviation describes how spread out individual measurements are around that average. Neither alone describes the distribution in full or the precision of a contrast, which is conveyed by its confidence interval.

7. Results Posted in the Registry

• Product B: mean 13.43 versus 14.98 on control; difference -1.55 (95% CI -4.22 to 1.12), standardized effect d = -0.31; z-test p = 0.256.
• Product C: mean 19.35 versus 14.98 on control; difference 4.37 (95% CI 1.22 to 7.52), standardized effect d = 0.75; z-test p = 0.006.
• Product D: mean 13.85 versus 14.98 on control; difference -1.13 (95% CI -3.50 to 1.24), standardized effect d = -0.25; z-test p = 0.350.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Orally Extracted of Nicotine

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Product B: mean 22.90 versus 19.10 on control; difference 3.80 (95% CI -1.61 to 9.21), standardized effect d = 0.37; z-test p = 0.169.
  • Product C: mean 21.90 versus 19.10 on control; difference 2.80 (95% CI -2.47 to 8.07), standardized effect d = 0.28; z-test p = 0.298.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Product B and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Product C and the control. The interval gives the range of effects that remain compatible with the data.

Urge to Use Emax

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Product B: mean 57.70 versus 61.70 on control; difference -4.00 (95% CI -15.51 to 7.51), standardized effect d = -0.19; z-test p = 0.496.
  • Product C: mean 66.10 versus 61.70 on control; difference 4.40 (95% CI -8.02 to 16.82), standardized effect d = 0.19; z-test p = 0.488.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Product B and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Product C and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes add different perspectives to the primary pharmacokinetic comparison. Percentage of orally extracted nicotine describes extraction at the stated 20-minute timeframe, while urge-to-use Emax summarizes a subjective measure over the scheduled assessment period. The posted means show variation among products for both measures, but their comparisons are unadjusted recalculations and do not constitute reported sponsor analyses.

Across the posted secondary comparisons, the confidence intervals include zero. The registry lists no reported analyses for these outcomes. The secondary results therefore do not provide a clearly separated, confirmatory pattern that should be read as equivalent in evidential weight to a prespecified primary analysis. They are best viewed as descriptive and exploratory context alongside the primary Cmax results.

These endpoints relate to the primary question but measure different things. Nicotine extraction is not a plasma concentration measure, and urge to use is not a pharmacokinetic endpoint. Similarity or difference in one measure does not guarantee the same pattern in another. Taken together, they can describe product-related observations across exposure, extraction, and subjective response, but they do not establish a single unified effect.

Unadjusted secondary findings carry less weight when multiple products and outcomes are examined because the chance of seeing an apparently noteworthy result can increase across repeated comparisons. The record does not report whether any multiplicity strategy was planned or applied. It also does not post sponsor-reported inferential analyses for these outcomes. Their confidence intervals and p-values should therefore be read as individual, unadjusted summaries, with emphasis on uncertainty rather than isolated thresholds.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Orally Extracted of Nicotine
• Urge to Use Emax

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports continuous outcomes as means with standard deviations. A mean is the arithmetic average of the observations included in an analysis. A standard deviation describes the variability of those observations around the mean. It is not the same as a confidence interval: the standard deviation characterizes participant-level spread, while a confidence interval expresses uncertainty about an estimated quantity such as a mean difference.

What does the mean difference represent?

The primary contrasts use Product A as the reference. For each other product, the reported mean difference is the other product's mean minus the Product A mean. A negative estimate indicates a lower posted mean for the compared product; a positive estimate indicates a higher posted mean. The comparison estimates are explicitly unadjusted recalculations from posted summary statistics. They are not identified in the registry as the sponsor's prespecified crossover analysis.

For the primary outcome, the recalculated mean differences are -1.55 ng/mL for Product B, 4.37 ng/mL for Product C, and -1.13 ng/mL for Product D, each relative to Product A. The corresponding unadjusted p-values are 0.256, 0.006, and 0.35. The uncertainty intervals should be considered alongside the point estimates: a point estimate alone does not indicate how precisely the contrast has been estimated.

What does a confidence interval tell the reader?

A confidence interval gives a range of estimates compatible with the data and the calculation method. In repeated use of the same method under its assumptions, intervals constructed this way would capture the underlying quantity at the stated confidence level at the specified long-run rate. It is not a range containing a known proportion of individual participants, nor does it assign a probability to the fixed true value after the interval has been calculated.

For a difference in means, zero represents no difference. An interval that includes zero is compatible with differences in either direction as well as no difference under the calculation. An interval that does not include zero indicates that the corresponding unadjusted summary-based interval is entirely on one side of zero. This interpretation concerns statistical compatibility, not clinical importance. The registry record does not define a threshold for a clinically important Cmax difference.

Why does the crossover design matter?

In a crossover study, each participant may contribute measurements under more than one product. Those measurements can be correlated within a participant, rather than behaving like observations from unrelated groups. A crossover analysis may use the within-participant relationship, and may also account for period or sequence. Taking product-specific means and standard deviations and calculating an unadjusted contrast does not, by itself, reproduce such a model. The registry record does not report the model or state how within-participant correlation, period, or sequence was handled.

This limitation is important when reading the recalculated standard errors, confidence intervals, and p-values: they reflect the summary-statistic comparison, not necessarily the most efficient or appropriate analysis for the crossover data. The record lists the outcome analysis population by product use, and notes that product-specific analyzed counts differ from participant-flow counts. It does not describe missing-data handling or explain why the analyzed count is lower for some product outcomes.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variation is greater than a model's assumptions allow. If a model understates variation, its standard errors may be too small and its intervals too narrow. If it allows for the observed variation appropriately, uncertainty can be represented more realistically. The posted primary outcome is continuous and is summarized with standard deviations; the registry does not report a model that assumes a particular dispersion structure or an over-dispersion adjustment. This concept is therefore background for evaluating statistical models, not a claim that over-dispersion was found in this trial.

How should p-values be read?

General statistical explanation: a p-value measures how unusual the data, or more extreme data, would be under a specified null hypothesis and model. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of a difference. Here, the p-values attached to the mean differences are unadjusted recalculations. The registry record does not report whether a multiplicity procedure was planned or used, and it lists no reported analyses. Consequently, these p-values should be interpreted as comparison-specific summaries, not as a complete confirmatory testing strategy.

The study's crossover structure, product-specific analysis populations, and multiple outcomes all make the analysis plan relevant. The registry record does not report the original sample-size assumptions, a prespecified statistical model, interim analyses, or missing-data procedures. Those absences do not invalidate the descriptive summaries, but they leave important questions about how the trial intended to estimate and test its treatment contrasts unanswered.

11. Confidence Intervals and Precision

Precision depends on the width of the confidence interval as well as the estimate's direction. A narrow interval indicates that the estimated contrast is more tightly bounded under the method used; a wide interval leaves a broader set of values compatible with the calculation. Precision is not the same as whether an estimate is clinically important, and it is not determined by the p-value alone.

For Product B versus Product A, the recalculated mean difference is -1.55 ng/mL, with a 95% confidence interval from -4.224 to 1.124. The interval crosses zero and covers values on both sides of no difference. For Product D versus Product A, the estimate is -1.13 ng/mL and the 95% confidence interval ranges from -3.498 to 1.238, also spanning zero. These comparisons leave uncertainty about both the direction and size of the underlying difference in the summary-based calculation.

For Product C versus Product A, the estimate is 4.37 ng/mL and the 95% confidence interval ranges from 1.224 to 7.516. This interval is entirely above zero. It still covers a range of possible contrast sizes, so the point estimate should not be read as exact. The interval describes uncertainty under the recalculation method, not uncertainty from a reported crossover model.

All three intervals are based on unadjusted summary-statistic recalculations. Their precision may differ from that of an analysis using the within-participant structure of the crossover, if such an analysis were specified. No sponsor-reported analysis is listed, and the registry record does not describe a prespecified model. These intervals therefore quantify the recalculated contrasts under their method rather than resolving every uncertainty about the study's treatment comparisons.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations calculated from the observed effect, not the original trial's design assumptions. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect targeted in each illustration is the stated fraction of the observed effect. The registry record does not report the original sample-size justification or its design assumptions.

The 80% power column gives the illustrative number of participants per arm that would be needed to have an 80% chance of detecting the specified effect under those assumptions, if that effect and model assumptions were correct. The 90% power column gives the corresponding illustration for a 90% chance. These are prospective planning quantities for hypothetical studies, not a measure of how likely the completed trial was to detect an effect.

Read across the effect scenarios with the same comparison in mind. Planning for 75% of the observed effect or 50% of the observed effect means targeting a smaller difference than the observed estimate. Smaller effects are harder to distinguish from random variation and therefore require more participants per arm under the stated assumptions. The figures also vary by contrast because the observed effect and variability differ across comparisons.

The calculations are not observed power. They should not be used to retrospectively label the completed study as adequately or inadequately powered, and they do not replace a design calculation based on a justified clinically meaningful target effect. The registry record does not report the original planning assumptions, so these illustrations cannot establish whether enrollment was chosen to meet a prespecified objective.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.550; pooled standard deviation σ = 4.965.
2. n = 2 × (1.96 + 0.842)² × 4.965² / -1.550² = 161.1, rounded up to 162 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1.55                      # observed difference in means
sigma <- 4.96490447748879                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(5452278)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 162 (80% power), 216 (90% power)
 75% of observed effect: n per arm = 287 (80% power), 384 (90% power)
 50% of observed effect: n per arm = 645 (80% power), 863 (90% power)
power.t.test: 162 
Simulated power at n = 162 per arm: 0.802 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and secondary outcomes, but it does not report a statistical analysis plan or a multiplicity adjustment. The primary comparisons include Product B, Product C, and Product D against Product A. Additional secondary comparisons are also posted. When several hypotheses are tested, the chance of at least one apparently unusual result can increase even if none of the underlying effects is real. Methods for controlling this issue may be prespecified, but no such method is reported in the registry record.

The posted p-values are explicitly unadjusted recalculations. They should not be interpreted as multiplicity-adjusted evidence, and no adjustment should be assumed. The registry record lists zero reported analyses. This means the available inferential values do not establish what testing hierarchy, if any, the sponsor intended to use. The primary endpoint may have a different role from secondary endpoints in a prespecified plan, but the record does not state such a plan.

Analysis populations also need attention. The primary endpoint description says the population comprises participants who used a specific product and notes that the analyzed number can differ from the number in each arm in participant flow. The displayed primary product analyses have counts of 27 for Product A, 26 for Product B, 26 for Product C, and 27 for Product D. The registry does not explain the missing product-specific observations or state how missing values were handled. It also does not report whether participants were excluded from an analysis or how incomplete crossover periods were treated.

The record does not report interim analyses, a missing-data method, or a statistical model for period, sequence, and within-participant correlation. It is therefore not possible to determine from the registry whether the posted calculations reproduce the intended analysis. These omissions are reasons to limit interpretation to the recorded descriptive summaries and unadjusted recalculations, not grounds to assume a particular unreported procedure.

15. 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 lists serious adverse events and other adverse events separately for each product group. For Product A, Product B, Product C, and Product D, the number at risk for serious adverse events is 27 in each group, and the number affected is 0 in each group. The death count is also 0 for every product group. No serious adverse event terms are listed.

These entries mean that the registry reports no participants affected by a serious adverse event in the displayed groups during the recorded study period. They do not establish that the risk of a rare event is absent, particularly in a study of this size and duration. The registry also lists other adverse events affecting 2 participants for Product A, 6 for Product B, 1 for Product C, and 3 for Product D.

The adverse-event figures should be read as registry counts, not as a controlled safety comparison. The record does not report event-level details, severity or relatedness for the other adverse events, or a comparative statistical analysis. The crossover exposure structure also means that simple group counts should not be assumed to represent independent parallel treatment groups. These data describe the recorded events and do not establish broader safety conclusions.

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

The posted results describe how the observed measurements differed across four oral nicotine products in a randomized crossover study of healthy volunteers. The mean Cmax was higher for Product C than for Product A in the posted product summaries, while Product B and Product D had lower posted means than Product A. The unadjusted recalculated confidence interval for Product C relative to Product A lies above zero; the intervals for Product B and Product D relative to Product A include zero.

Those patterns do not answer every question about the products. The results concern maximum observed plasma nicotine concentration, not all aspects of nicotine exposure, product use, or health. The registry lists extraction and urge-to-use outcomes as secondary measures, but those are different constructs. No treatment recommendation follows from a relative bioavailability comparison, and these data alone do not establish clinical benefit or harm.

The study also has a specific setting and population: healthy snus or nicotine pouch users under clinic confinement conditions. The record does not report evidence for other populations or use settings. It does not report longer-term outcomes, and the recorded concentration measurements extend only through 8 hours after product use began. Extrapolation beyond the measured setting and outcomes is not supported by the registry information.

Statistically, the contrasts are unadjusted recalculations from summary statistics. The record does not report the sponsor's statistical model, how the crossover correlation was handled, or whether multiple comparisons were controlled. The intervals and p-values should therefore be interpreted as summaries under the stated recalculation, rather than definitive results from a documented analysis plan. The record's absence of reported analyses also means the posted statistics cannot be checked against a prespecified analysis from the registry entry alone.

The most defensible reading is descriptive: the product means differ, and the precision of those differences varies. A confidence interval communicates uncertainty in the estimated contrast, but it does not show how much difference would matter clinically. The registry record does not define such a threshold. These results can inform understanding of observed relative exposure under the study conditions, while leaving clinical significance, broader applicability, and the intended inferential analysis unresolved.

17. Why This Trial Matters Statistically

This trial is statistically instructive because a crossover design and a simple product-by-product summary are not the same thing as a crossover analysis. Participants used products in different orders, and observations from the same participant may be related. Product means and standard deviations are useful descriptions, but they do not show how the within-participant comparison, period, or sequence was handled. The registry record does not report that analytical detail.

The record also illustrates why estimates, intervals, and p-values should be considered together. Product C's estimated contrast with Product A is positive and its unadjusted interval lies above zero, whereas the intervals for Product B and Product D span zero. Those distinctions describe the posted calculations, but they do not establish clinical importance or resolve the impact of unadjusted multiple comparisons.

A further statistical lesson is the distinction between planning and retrospective power. The planning illustrations use fractions of observed effects and specified assumptions, while the trial's original design assumptions are not reported in the registry record. Such illustrations can show how a hypothetical future study's size changes as its target effect changes. They do not explain why the completed trial enrolled its participants or measure the trial's observed power.

Finally, the registry makes analysis-population variation visible: product-specific counts are not identical for every outcome. That matters in a crossover study because missing measurements or incomplete periods can affect the available comparisons. The record does not explain those differences or the approach to missing data. Clear reporting of analysis populations, models, multiplicity, and missing-data handling is essential for readers to judge how closely the reported statistics answer the trial's intended question.

18. 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 main limitation for statistical interpretation is that the registry record does not report the planned analysis model. The study is a crossover, but the posted contrasts are unadjusted recalculations from product-level summary statistics. The record does not say whether a sponsor analysis accounted for repeated observations within participants, product period, or sequence. The uncertainty estimates may therefore not represent the intended crossover comparison.

The registry lists no reported analyses and does not report a multiplicity strategy. Several products and outcomes are considered, so unadjusted p-values should not be treated as a complete confirmatory testing framework. The record also does not describe how missing measurements were handled. Product-specific analysis counts vary, and the primary endpoint description explicitly distinguishes product-specific analyzed populations from participant-flow counts.

Blinding is not consistently described: the official title and study summary call the study single-blind, but the masking field states none. The record does not clarify which procedures, if any, were blinded. It also does not provide details about sequence allocation, eligibility criteria beyond healthy snus or nicotine pouch use, or the original sample-size rationale.

The endpoints are limited to pharmacokinetic, extraction, and subjective measures recorded during the study. The registry does not report longer-term outcomes or define a clinically important Cmax difference. As a result, the size and practical meaning of the observed contrasts cannot be established from the posted statistics alone. These limitations narrow the conclusions to the observed short-term summaries and the assumptions of the unadjusted calculations.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Relative Bioavailability Study of Nicotine Delivery From Selected Oral Nicotine Products — NCT05452278.
• Registry record last updated 2026-03-09; status last verified 2026-02.
• Results first posted 2025-09-26.
• 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.

22. Record Summary

NCT05452278 is a completed randomized crossover study of relative nicotine bioavailability from Product A, Product B, Product C, and Product D in healthy snus or nicotine pouch users. The registry reports enrollment of 27 and describes a four-day confinement period in which participants followed different product orders.

The primary outcome is maximum observed plasma nicotine concentration, reported as product-specific means and standard deviations, with unadjusted recalculated comparisons against Product A. Secondary outcomes are percentage of orally extracted nicotine and urge-to-use Emax. The registry also reports adverse-event counts, including zero serious adverse events and zero deaths in each product group.

The record does not list sponsor-reported analyses or report the original statistical plan, multiplicity handling, crossover model, or missing-data approach. The results are therefore best read as descriptive summaries and unadjusted statistical contrasts, with the posted confidence intervals indicating their uncertainty under that calculation.