Potential Influence of Esomeprazole on the Pharmacokinetics of Pritelivir: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Potential Influence of Esomeprazole on the Pharmacokinetics of Pritelivir (NCT05513625), a non-randomized phase 1 study. The primary outcome is PK - Cmax.

2. Clinical Question

3. Trial Design

This completed Phase I trial is described as single-center, open-label, and fixed-sequence, with nonrandomized allocation. The record gives enrollment as 16 and lists the condition as HSV infection. It identifies AiCuris Anti-infective Cures AG as the sponsor. The recorded start date is 2020-07-13 and the primary completion date is 2020-10-13.

The two regimen descriptions are a single 100 mg pritelivir dose on Day 1, and 40 mg qd ESO from Day -3 to Day1 together with a single 100 mg pritelivir dose on Day 1. This design addresses a pharmacokinetic question about pritelivir exposure in the presence of ESO. Because allocation is nonrandomized and the study is fixed-sequence, the regimens are not a randomized comparison. The registry record does not report enough participant-level scheduling detail to determine whether the same individuals received both regimens, or to describe any period or sequence effects.

Open-label means treatment assignment was not masked as described in the record. The record does not report a blinding procedure. It lists seven outcome measures, including primary Cmax and secondary pharmacokinetic measures such as Tmax and Tlag, λz, t1/2z, CL/F, and V d/F. The primary endpoint timeframe is 15 days. Details of visit timing, sample collection, eligibility criteria, dose administration conditions, and analysis populations are not reported in the registry record.

The status is completed, but completion does not by itself indicate that results for every planned measure were posted. Numerical primary endpoint results and the analysis methods used for them are not reported in the registry record. The safety record gives at-risk and affected counts for each regimen, which can be described separately from the missing pharmacokinetic results.

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: 16 subjects enrolled in PTV 100 mg (T1), 15 completed. The 15 completed were enrolled into ESO 40 mg/PTV 100 mg (T2)

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety Set

6. Primary Endpoint

The registry lists the primary outcome as PK - Cmax, measured over 15 days.

The primary endpoint is pritelivir Cmax, defined in the registry record as the maximum observed plasma concentration. It is a continuous pharmacokinetic measure, summarized as a mean with standard deviation, over a 15-day timeframe.

As a general pharmacokinetic concept, Cmax describes the peak concentration observed after a dose. It can help characterize the concentration profile and is one measure used when evaluating whether another medicine may influence drug exposure. It is not a complete description of exposure: other pharmacokinetic measures can characterize timing, elimination, or the concentration profile in different ways. The registry record lists secondary measures including Tmax and Tlag, λz, t1/2z, CL/F, and V d/F.

A mean describes the average measured Cmax in the analyzed observations. A standard deviation describes the spread of those observations around their mean; it is not a confidence interval and does not by itself show the precision of an estimated treatment difference. To assess a contrast between regimens, readers would also need the relevant estimates and, ideally, an uncertainty measure for that contrast.

Although the endpoint definition and summary method are recorded, the numerical Cmax results, the number of observations analyzed, and an estimated contrast are not reported in the registry record. Consequently, the endpoint’s direction, magnitude, variability, and precision cannot be described from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a continuous primary endpoint: Cmax, the maximum observed plasma concentration of pritelivir. It specifies the mean as the summary measure and standard deviation as the dispersion measure. These describe the observed distribution in different ways. The mean gives its average level, while the standard deviation reflects how widely individual observed values vary around that average. Neither quantity alone expresses the uncertainty in a comparison between regimens.

What a comparison would need to show

For a treatment contrast, an estimate of each regimen’s Cmax, or a directly estimated contrast, would be needed. An uncertainty interval around the contrast would help show the range of values reasonably compatible with the data under the analysis assumptions. A confidence interval is a statistical method for expressing uncertainty in an estimate; it is not a range containing a fixed proportion of individual measurements. The registry record does not report Cmax estimates, a contrast, or a confidence interval.

A significance test, if used, would address compatibility of the data with a specified null hypothesis under its assumptions. A p-value would not measure the size or importance of an effect, and it would not describe the probability that the null hypothesis is true. No p-value or inferential test for Cmax is reported in the registry record. The appropriate analysis cannot be reconstructed from the endpoint definition alone.

Design and allocation

The trial is described as nonrandomized, open-label, and fixed-sequence. In general, random allocation can help balance measured and unmeasured participant characteristics across groups, whereas a nonrandomized comparison may be more vulnerable to differences associated with how regimens are assigned. This general consideration does not establish that any particular bias occurred in this trial. The record does not report the allocation procedure beyond its nonrandomized classification.

A fixed-sequence design can involve observations collected in a specified order. In general, interpretation may depend on whether the same participants contribute observations under multiple exposures, the timing between exposures, and whether period or sequence effects are considered. The arm descriptions alone do not establish the participant-level sequence, any washout interval, or the statistical handling of repeated observations. These details are not reported in the registry record, so it is not appropriate to assume an independent-groups or paired analysis.

Variability and pharmacokinetic measures

Pharmacokinetic measurements can vary among participants and across measurement times. The standard deviation is one descriptive measure of variability for the primary continuous outcome. If the distribution is skewed or otherwise does not fit an analysis model, a mean-based analysis may not fully represent the data; choosing an analysis requires knowledge of the observed values and the prespecified method. The distribution of Cmax and any transformation or alternative summary are not reported in the registry record.

The listed secondary measures describe other aspects of pharmacokinetics. As general concepts, Tmax and Tlag concern timing, λz and t1/2z relate to the terminal elimination phase, and CL/F and V d/F are apparent pharmacokinetic parameters. Their definitions help explain why a study may assess more than peak concentration, but the record does not post numerical results for these measures. It also does not report the calculation procedures or model specifications used for them.

Planning illustrations

The record describes planning illustrations based on a stated fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It specifies that time-to-event illustrations use a total event count and other illustrations use participants per arm. These assumptions describe hypothetical planning calculations; they are not results from the trial and are not observed power. The numerical observed effect and numerical planning outputs are not reported in the registry record, so their values and sensitivity cannot be assessed from the record. Any such illustration depends on the assumed effect and analysis conditions and should not be interpreted as evidence that the completed trial had a particular probability of detecting an effect.

More broadly, the registry record does not report a statistical analysis plan, the model used for the primary endpoint, methods for handling repeated observations, covariate adjustment, or the approach to missing pharmacokinetic measurements. Without those details and without numerical endpoint results, readers cannot independently reproduce or evaluate the precision of the primary comparison.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("100 mg Pritelivir", "40 mg qd ESO and 100 mg Pritelivir")
n   <- c(16, 15)
m   <- c(1102, 282)
sp  <- c(421, 141)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  100 mg Pritelivir  16  1102.000  421.000  877.665  1326.335
CARM  40 mg qd ESO and 100 mg Pritelivir  15  282.000  141.000  203.917  360.083

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists seven outcome measures, including primary Cmax and secondary pharmacokinetic measures. When a study evaluates multiple outcomes, the chance of finding at least one apparently unusual result can depend on how many comparisons are made and how they are interpreted. General statistical approaches can control or describe this multiplicity, but the record does not report whether any adjustment, hierarchy, or other multiplicity strategy was planned or used. The primary outcome is identified, but that alone does not explain how secondary results were to be interpreted.

The record reports zero analyses and does not give numerical endpoint results. It therefore does not show which outcomes were analyzed, whether all intended analyses were completed, or whether any results were selected for posting. The statistical analysis plan and any interim analysis procedures are not reported in the registry record.

Missing-data handling is also not reported. The registry record does not state how missing concentration measurements, incomplete sampling profiles, or participants without usable pharmacokinetic observations were handled. It does not provide an endpoint-specific analysis population or the number of observations contributing to Cmax. Enrollment of 16 does not establish that all enrolled participants contributed to every outcome.

These omissions limit assessment of possible selection and analysis effects. In general, missingness can matter when the reason data are unavailable is related to the outcome or treatment, and different handling methods can lead to different estimates. That is a general methodological concern, not evidence that missing data occurred or affected this trial. The record does not report enough information to determine whether data were missing, how much, or whether any analysis addressed it.

12. 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 safety record reports serious adverse events, other adverse events, and deaths by regimen. For 100 mg pritelivir, 16 were at risk for serious adverse events and 0 were affected; 16 were at risk for other adverse events and 2 were affected. For 40 mg qd ESO and 100 mg pritelivir, 15 were at risk for serious adverse events and 0 were affected; 15 were at risk for other adverse events and 4 were affected. Deaths were 0 in each group.

These are descriptive counts, not a randomized comparison of adverse-event risk. The nonrandomized allocation and fixed-sequence design mean the groups should not be read as interchangeable control groups. The counts also do not indicate event severity among the other adverse events, timing, recurrence, relatedness to study treatment, or the specific event terms. Serious adverse event terms are not listed in the record.

No serious adverse events or deaths are recorded in these group summaries, but that observation does not establish that such events could not occur or characterize risks beyond the recorded participants and observation period. The safety figures should be read alongside the limited group sizes and the absence of a detailed event narrative. The registry record does not report further safety analysis or comparative estimates.

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

The registry record supports a description of the trial’s objective and design. It was a completed Phase I study investigating the potential influence of ESO on pritelivir pharmacokinetics and the safety and tolerability of pritelivir. The primary measure was Cmax, defined as maximum observed plasma concentration, with mean and standard deviation specified over a 15-day timeframe. The record also identifies secondary pharmacokinetic measures and provides adverse-event counts by regimen.

What the record does not establish is the result of the central pharmacokinetic comparison. Numerical Cmax values, a contrast between regimens, and uncertainty estimates are not reported in the registry record. Thus, it is not possible to state whether the observed Cmax was higher or lower with ESO, how large any difference was, or how precisely it was estimated. The endpoint definition is not itself an outcome result.

The study design also limits what can be inferred from a simple comparison of the regimen descriptions. The record identifies nonrandomized allocation and a fixed sequence; it does not provide sufficient details about individual participant exposure order or analysis to establish whether observations were paired or independent. No causal interpretation or adjustment for possible design-related effects can be assessed from the information reported.

The safety counts show no recorded serious adverse events or deaths in either group, alongside other adverse events affecting 2 in the pritelivir group and 4 in the ESO and pritelivir group. These descriptive counts do not establish a comparative safety effect, explain the nature of the events, or demonstrate absence of risk. They are limited to the recorded groups and do not substitute for detailed safety results.

Overall, the record documents the question asked and some study characteristics, but it does not contain the numerical primary pharmacokinetic findings needed to answer that question quantitatively. Conclusions about the direction, magnitude, precision, or clinical importance of an exposure difference are not supported by the posted results.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction between a stated research question and a reported statistical result. The registry record clearly identifies Cmax as the primary endpoint and describes the intended pharmacokinetic comparison. Yet the endpoint’s numerical results and a direct comparison are not reported. Without estimates and uncertainty, readers cannot quantify what the study observed or assess how much uncertainty surrounds the comparison.

It also highlights why design details matter in pharmacokinetic research. A fixed-sequence, nonrandomized study is not interpreted in the same way as a randomized parallel-group trial. Whether participants contribute data under one or both regimens, how order and timing are handled, and what model is used can all affect the meaning of a contrast. Those details are not reported in the registry record, so the analysis structure cannot be verified from the record.

The trial further shows the difference between descriptive safety counts and comparative evidence. Counts of affected participants are useful for recording what was observed, but they do not, on their own, explain event type or establish a difference in risk. Denominators, group assignment, follow-up, and event detail all shape interpretation.

Finally, planning illustrations should not be confused with evidence from the completed study. A calculation based on an assumed fraction of an observed effect is a planning exercise, not observed power or a substitute for a reported endpoint estimate. Clear posting of results, analysis populations, and methods is necessary for readers to evaluate both precision and limitations. In this case, the record’s design and safety information can be described, while the primary pharmacokinetic result remains unavailable in the registry 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 most direct limitation is that numerical results for the primary endpoint are not reported in the registry record. Without Cmax estimates, variability values, or an estimated contrast, the magnitude and precision of the comparison cannot be assessed. The record also lists zero analyses, so it does not provide a statistical result for the primary endpoint or the listed secondary measures.

The allocation is nonrandomized, and the trial is described as fixed-sequence. The record does not explain participant-level exposure order, whether observations were collected from the same participants under both regimens, or how period and sequence effects were considered. It is therefore not possible to determine the appropriate comparison structure or evaluate whether relevant design features were addressed in analysis.

The registry record does not report participant characteristics, eligibility criteria, endpoint-specific analysis populations, or the number of usable pharmacokinetic profiles. It does not describe missing measurements or their handling. Although enrollment is 16, that number does not establish the number contributing to each endpoint. The statistical analysis plan, model specifications, and any multiplicity approach are also not reported.

Safety reporting is limited to counts of participants at risk and affected, plus deaths. The record does not provide event terms, severity details for other adverse events, timing, duration, or treatment relatedness. The group summaries are descriptive and do not support a randomized comparison. These limitations concern what can be assessed from the registry record; they do not establish that a particular bias, missing-data problem, or adverse event occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Potential Influence of Esomeprazole on the Pharmacokinetics of Pritelivir — NCT05513625.
• Registry record last updated 2024-02-22; status last verified 2022-09.
• Results first posted 2023-09-15.
• 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

The registry record describes a completed, single-center, open-label, fixed-sequence Phase I trial with nonrandomized allocation and enrollment of 16. It concerns HSV infection and investigates the effect of ESO on pritelivir pharmacokinetics, as well as pritelivir safety and tolerability.

The listed regimens are a single 100 mg pritelivir dose on Day 1 and 40 mg qd ESO from Day -3 to Day1 with a single 100 mg pritelivir dose on Day 1. The primary endpoint is Cmax, summarized as a mean with standard deviation over 15 days. Secondary measures include Tmax and Tlag, λz, t1/2z, CL/F, and V d/F.

Numerical pharmacokinetic results and analyses are not reported in the registry record. Safety summaries record no serious adverse events or deaths in either regimen group, and other adverse events affecting 2 of 16 and 4 of 15, respectively. The record does not report a statistical analysis plan, analysis populations, or missing-data methods.