Pharmacokinetics Of Sildenafil Orally Disintegrating Tablet Formulation Given With Or Without Food.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics Of Sildenafil Orally Disintegrating Tablet Formulation Given With Or Without Food. (NCT01254396), a randomized phase 1 study. The primary outcome is Maximum Observed Plasma Concentration (Cmax).

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, open-label crossover study with enrollment of 12. Its official title describes healthy older male subjects and evaluates the pharmacokinetics and safety of sildenafil orally disintegrating tablet administered without water under fed compared with fasted conditions. The study status is completed. The recorded start was 2010-12, and primary completion was 2011-01.

The two treatment conditions were sildenafil 50 mg without water while fasted and sildenafil 50 mg without water while fed. The crossover design makes the conditions the focus of comparison within the study rather than comparing separate parallel groups only. In general, crossover designs can account for stable differences between participants because each participant may contribute information under more than one condition. The registry record does not describe treatment order, period length, washout, or the method used to account for period or sequence effects, so those details cannot be assessed from this record.

The study was open label, with no masking reported. The primary pharmacokinetic analysis population included randomized and treated participants who had at least one primary pharmacokinetic parameter in at least one treatment period. Each treatment group has 12 participants in the posted Cmax results. The record does not provide a separate account of exclusions or missing measurements.

The primary endpoint was Cmax. Secondary outcomes listed in the registry were time to reach maximum observed plasma concentration, area under the curve from time zero to extrapolated infinite time, and plasma decay half-life. The registry lists five outcome measures overall, but the information available for interpretation is not equally detailed for all outcomes. The analysis method is not specified in the record.

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 Intervention Period

Washout Period (at Least 1 Day)

Second Intervention Period

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic parameter analysis population included all randomized and treated participants who had at least 1 of the pharmacokinetic parameters of primary interest in at least 1 treatment 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 Maximum Observed Plasma Concentration (Cmax), measured over 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 14 hrs post-dose.

The primary endpoint, maximum observed plasma concentration (Cmax), is the highest measured concentration of sildenafil in plasma over the sampling period. It is a pharmacokinetic measure: it describes the peak concentration reached, not a clinical outcome or a direct measure of symptom change. The registry reports Cmax in ng/mL and summarizes each treatment condition using a geometric mean and standard deviation.

Concentration samples were scheduled from pre-dose through 14 hrs post-dose, at the listed times 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 14 hrs post-dose. This sampling schedule is intended to capture the concentration profile after dosing and identify the largest observed value. The endpoint is useful when comparing how dosing conditions relate to the peak plasma concentration. It does not by itself describe total drug exposure, the timing of the peak, or how quickly concentrations decline; those are addressed by other pharmacokinetic measures.

In general, the geometric mean is a way of summarizing measurements that are positive and may be skewed, while a standard deviation describes spread on the scale used for the reported summary. These summaries do not show each participant’s concentration profile. The registry does not provide individual-level Cmax values or the calculation details for the adjusted comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry presents condition-specific Cmax geometric means and standard deviations, plus a ratio of adjusted means and a 90% confidence interval. It does not name the statistical method used to obtain the adjusted comparison. The following points explain the general meaning of these statistics, rather than asserting which particular model was used.

What does a geometric mean summarize?

In general, a geometric mean summarizes positive measurements by working with their logarithms and then expressing the center on the original scale. This can be useful for pharmacokinetic concentrations, which may be asymmetric rather than distributed evenly around an arithmetic average. The reported geometric means are 292.6 ng/mL for the fasted condition and 121.0 ng/mL for the fed condition. These are group summaries; they do not reveal the range of individual observations or how each participant’s values changed across conditions.

The record labels the accompanying spread as standard deviation. A standard deviation describes variability, but interpretation depends on the scale on which it was calculated. The registry does not state whether the standard deviation was calculated on the original or transformed scale. For that reason, the spread values should be read using the record’s label rather than treated as a confidence interval or as a direct measure of uncertainty in the ratio.

What does the ratio and confidence interval mean?

A ratio of adjusted means compares estimated means after adjustment according to a statistical model. In general, adjustment may account for features of the study design or other modeled terms. The registry reports a ratio of adjusted means of 41.35 and a 90% confidence interval from 32.40 to 52.76. The direction of the ratio and the adjustment terms are not reported in the registry record. The result therefore cannot be independently reconstructed from the two geometric means alone.

In general, a confidence interval represents the range of estimates compatible with the observed data under the method’s assumptions, at the stated confidence level. It is not a range containing a specified proportion of individual participants’ measurements, and it is not a probability statement about the fixed true value. The interval’s precision also depends on the analysis and data structure. Because the method is not named, readers cannot assess model-specific assumptions from the registry entry.

Why does the crossover design matter?

In general, a crossover study compares treatment conditions within participants, which can reduce the influence of stable differences between people. Such a design also requires care with treatment sequence and time period: a participant’s response in a later period could be affected by the earlier treatment or by changes over time. Statistical analysis may need to account for the paired nature of the measurements and relevant period or sequence features. The registry identifies the study as randomized and crossover but does not describe the randomization sequence, washout, period structure, or analysis of these effects. Those details are not reported in the registry record and should not be inferred.

The study is open label, meaning masking was not reported. For an objective laboratory concentration measure, the direct measurement is not a subjective symptom rating, but open-label status remains part of the design context. The registry does not describe laboratory procedures, assay performance, or whether concentration assessments were conducted without knowledge of treatment condition.

What can and cannot be inferred from the reported statistics?

The arm summaries describe Cmax under each condition, and the adjusted ratio gives the registry’s comparative estimate. The confidence interval indicates uncertainty around that estimate under the sponsor’s analysis, but no p-value is reported. A confidence interval can help readers judge precision; it does not substitute for a prespecified clinical or pharmacokinetic criterion. In general, demonstrating equivalence or similarity requires a defined margin and an analysis designed to evaluate that margin. Neither an equivalence margin nor such a decision rule is reported.

Planning sample-size illustrations, when calculated from an observed effect, are not observed power and do not establish what the trial was designed to detect. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. These are planning assumptions, not evidence of the original design rationale. The sample-size justification and any original design calculation are not reported in the registry record.

More broadly, statistical interpretation depends on the analysis population, completeness of measurements, model specification, and handling of missing data. The record defines the primary pharmacokinetic analysis population as randomized and treated participants with at least one primary parameter in at least one treatment period. It does not provide individual observations or further methodological details, which limits independent assessment of the reported adjusted estimate.

10. Analyses Reported by the Sponsor

The registry reports a ratio of adjusted means of 41.35 with a 90% confidence interval from 32.40 to 52.76. It does not report the method used to calculate that estimate, the adjustment terms, the ratio direction, or a p-value. The condition-level Cmax geometric means are reported separately as 292.6 ng/mL under fasted conditions and 121.0 ng/mL under fed conditions.

No separate recalculated ratio is reported in the registry record, so there is no independent recalculation to compare with the sponsor’s estimate. The condition-level summaries alone are not enough to reproduce an adjusted ratio, particularly without the paired participant-level data and analysis specification. The record marks discrepancy as false, so it does not flag a conflict between the sponsor’s analysis and a recalculation. The posted estimate should therefore be read as the registry’s reported analysis, while recognizing that its statistical method is not described in the record.

The reported confidence interval conveys uncertainty under the sponsor’s analysis, but it does not establish similarity or equivalence without a prespecified margin and decision rule. Those are not reported in the registry record. The analysis should not be assigned a more specific interpretation than the information allows.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists Cmax as the primary outcome and identifies three secondary outcomes: time to reach maximum observed plasma concentration (Tmax), area under the curve from time zero to extrapolated infinite time, and plasma decay half-life. It also lists five outcome measures overall and reports three analyses. However, the available information does not specify how many hypotheses were formally tested or whether the primary and secondary analyses were organized into a testing hierarchy.

Multiplicity arises in general when several outcomes, comparisons, or analyses are examined. If many statistical tests are interpreted without a plan to control the overall false-positive rate, the chance of at least one apparently notable result can increase. Statistical approaches can address this issue, but the approach depends on the study’s prespecified analysis plan. Adjustment for multiplicity, a testing hierarchy, and prespecified distinctions among confirmatory and exploratory outcomes are not reported in the registry record. No p-value is reported for the primary comparison, so multiplicity-adjusted inference cannot be assessed from the posted information.

The primary pharmacokinetic analysis population is defined as all randomized and treated participants who had at least one primary pharmacokinetic parameter of interest in at least one treatment period. That definition describes who could contribute to the primary analysis, but it does not explain how missing measurements were handled or whether participants with incomplete data were excluded from particular estimates. Missing-data rules, imputation methods, and sensitivity analyses are not reported in the registry record.

The record reports 12 participants in each treatment condition for Cmax. It does not provide a participant flow account showing how many randomized participants completed each period or contributed paired measurements. Nor does it report reasons for missing observations or withdrawals. In general, a crossover analysis can be affected when measurements are unavailable for one treatment period, because incomplete pairs may contribute differently from complete pairs. Without further detail, the impact of missing or incomplete measurements cannot be evaluated.

The sample-size justification, any interim analyses, and the full statistical analysis plan are not reported in the registry record. Any planning illustration based on the observed effect describes hypothetical planning under stated assumptions; it is not observed power and does not supply the missing original design rationale.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 safety figures are reported separately for the fasted and fed treatment conditions. For each condition, 12 participants were at risk for serious adverse events, and zero serious adverse events were recorded. The registry lists no top serious adverse event terms. These are counts in the posted safety results, not evidence that serious events are impossible or that the conditions have identical safety profiles.

For other adverse events, 12 participants were at risk in each condition and 3 were affected in each. The record does not provide event descriptions or severity details in the listed safety information. Deaths are recorded as null for both conditions; that means a death count is not reported in the registry record, rather than supplying a numerical count.

In general, safety counts from a small study provide limited information about uncommon events and do not by themselves establish comparative safety. The reported counts should be read in the context of the study’s enrollment, duration, population, and the adverse-event definitions used. The registry does not give additional detail on event ascertainment or follow-up in the information available for these figures. These results describe recorded events in this study and should not be treated as a broader safety conclusion.

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

The main statistical result is a comparison of the peak plasma concentration of sildenafil 50 mg orally disintegrating tablet taken without water under fed and fasted conditions. The posted geometric means are 121.0 ng/mL for fed dosing and 292.6 ng/mL for fasted dosing. The registry also reports an adjusted means ratio of 41.35 with a 90% confidence interval from 32.40 to 52.76. The record does not state the ratio direction or analysis method, so that estimate should not be given an inferred direction or reconstructed from the group summaries.

These results describe pharmacokinetics, not clinical benefit. Cmax concerns the maximum observed plasma concentration; it is not a measure of symptom improvement, treatment success, or long-term outcome. The registry’s stated aim was to assess whether pharmacokinetic properties were similar with and without food. However, a similarity conclusion requires a defined margin or criterion, and none is reported. A confidence interval alone does not establish that two conditions are equivalent.

The study enrolled 12 healthy older male subjects and was open label. Its findings therefore apply directly to the study conditions and analysis population described in the registry, not automatically to other populations, formulations, or use circumstances. The condition field lists Erectile Dysfunction, but the official title identifies healthy older male subjects; the record does not establish that the participants had that condition.

The registry identifies secondary pharmacokinetic outcomes involving Tmax, total exposure through extrapolated infinite time, and plasma decay half-life. Their numerical results are not included in the registry record for this interpretation. The primary Cmax result cannot stand in for those other dimensions of the concentration profile. Likewise, the recorded adverse-event counts describe this study and do not determine safety in a broader population.

Overall, the posted information supports a descriptive account of Cmax by feeding condition and a reported adjusted comparison with uncertainty. The absent method details, ratio direction, equivalence criterion, and additional analysis information limit stronger interpretation. No conclusion about clinical effectiveness or the suitability of either dosing condition follows from these pharmacokinetic figures alone.

14. Why This Trial Matters Statistically

This trial is statistically interesting because a crossover design addresses a different question from a conventional parallel-group comparison. In general, participants can serve as their own reference across treatment conditions, which can reduce the influence of stable between-person differences. That feature can be useful for pharmacokinetic comparisons, where measured concentrations may vary across individuals. At the same time, it makes treatment sequence, period effects, and carryover important design and analysis considerations.

The registry records randomization and crossover structure but does not describe sequence allocation, treatment periods, washout, or the statistical model. This illustrates why a design label alone is not enough to reproduce or fully assess an analysis. The reported condition-specific geometric means and adjusted ratio answer related but distinct descriptive questions; the ratio’s model details are essential to understanding exactly how the comparison was formed.

The endpoint also highlights the distinction between a pharmacokinetic result and a clinical result. Cmax captures the observed peak concentration, while Tmax, area under the curve, and half-life describe other parts of the concentration-time profile. A difference in one parameter does not automatically determine the others or imply a difference in a clinical outcome. Interpreting the stated goal of similar pharmacokinetics also requires a prespecified similarity criterion, which is not reported in the registry record.

Finally, the study shows how uncertainty and design limitations should be read together. The 90% confidence interval gives a range around the reported adjusted estimate under an analysis whose method is not specified. The modest enrollment and lack of reported analysis details constrain how much can be inferred. Statistical reporting is most useful when readers can connect the endpoint, design, analysis population, model, missing-data handling, and decision criterion; several of those details are absent from this record.

15. 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 does not identify the statistical method used for the adjusted means ratio or explain which terms were included in the adjustment. It also does not state the ratio direction. As a result, the reported estimate cannot be fully interpreted or reproduced from the arm-level geometric means. Participant-level data and the analysis specification are not reported in the registry record.

Important crossover details are absent, including treatment sequence, period structure, washout, and handling of possible period or carryover effects. The record does not describe the assay, laboratory quality procedures, or whether concentration measurements were assessed without knowledge of treatment condition. These omissions prevent a full review of design implementation and analysis assumptions.

The registry does not provide an equivalence margin or a formal criterion for judging whether pharmacokinetic properties are similar. It reports no p-value for the primary comparison. The multiplicity approach, original sample-size justification, interim analyses, and complete statistical analysis plan are not reported in the registry record. Missing-data handling and sensitivity analyses are also not described.

The study enrolled 12 healthy older male subjects. This limits the direct scope of the findings to the population and dosing conditions recorded; generalization beyond them is not established by this study. The open-label design is another feature to consider, even though Cmax is a laboratory-based endpoint. The safety results provide counts but little event-level detail, and deaths are not reported numerically. Finally, the numerical results for the listed secondary pharmacokinetic outcomes are not available for this interpretation, so the broader concentration-time profile cannot be assessed from Cmax alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacokinetics Of Sildenafil Orally Disintegrating Tablet Formulation Given With Or Without Food. — NCT01254396.
• Registry record last updated 2021-02-01; status last verified 2021-01.
• Results first posted 2012-02-08.
• 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.

19. Record Summary

NCT01254396 is a completed Phase 1 randomized, open-label crossover study of sildenafil orally disintegrating tablet taken without water under fed and fasted conditions. It enrolled 12 healthy older male subjects. The primary endpoint was maximum observed plasma concentration (Cmax), with condition-specific geometric means of 292.6 ng/mL for fasted dosing and 121.0 ng/mL for fed dosing. The registry reports a ratio of adjusted means of 41.35 with a 90% confidence interval from 32.40 to 52.76.

The record does not report the analysis method, ratio direction, equivalence criterion, missing-data approach, or original sample-size justification. Serious adverse events were recorded for zero participants in each condition; other adverse events affected 3 participants in each. These findings describe the posted results and do not establish clinical effectiveness, equivalence, or broader safety.