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 A Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of Vonoprazan in Adolescents With Symptomatic Gastroesophageal Reflux Disease (NCT05343364), a randomized phase 1 study. The primary outcome is Maximum Observed Drug Concentration at Steady State (Cmax-ss) of Vonoprazan.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05343364 |
| Phase | Phase 1 |
| Condition | Gastroesophageal Reflux |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Phathom Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Adolescents with symptomatic gastroesophageal reflux disease (GERD), as described in the registry record.
Intervention
Vonoprazan 10 mg once daily for 14 days, or vonoprazan 20 mg once daily for 14 days.
Comparator
The other vonoprazan dose group. The registry record describes a randomized, parallel-group study, not a comparison with placebo or another drug.
Primary question
What maximum observed plasma concentration at steady state (Cmax-ss) was measured for vonoprazan in the adolescent pharmacokinetic population at each dose?
The primary objective was to evaluate vonoprazan’s pharmacokinetic profile in adolescents with symptomatic GERD. Pharmacokinetics describes how drug concentrations change over time in the body. Cmax-ss focuses on the maximum observed concentration after repeated dosing has reached a steady state, rather than on symptom response or a clinical outcome.
The study also concerned pharmacodynamics and safety, as reflected in its title. The registry record identifies the number of participants experiencing adverse events as a secondary outcome. It does not report a symptom-control or other efficacy endpoint among the posted results. The central statistical question is therefore descriptive: what concentrations were observed in the evaluable participants assigned to each dose? The results can characterize concentrations in this study’s pharmacokinetic set, but the record does not provide a posted statistical test comparing the dose groups.
3. Trial Design
The registry describes a Phase 1, randomized, parallel-group, open-label, multicenter study of vonoprazan in adolescents with symptomatic GERD. Enrollment was 24, and the record is marked completed. Participants were assigned to vonoprazan 10 mg once daily or vonoprazan 20 mg once daily, with each treatment scheduled for 14 days. Because the study was open-label, masking is listed as none. The registry record does not report further details about randomization procedures, such as sequence generation or allocation concealment.
The primary endpoint was maximum observed drug concentration at steady state. Plasma pharmacokinetic parameters were estimated using a nonlinear mixed effects model from concentration-time data for evaluable participants. The endpoint population is described as the pharmacokinetic set, including participants with at least one measurable concentration result. The reported group sizes for this endpoint are 9.0 in the 10 mg group and 8.0 in the 20 mg group. Those endpoint group sizes are not the same information as overall enrollment; the registry record does not explain the difference.
Blood sampling was scheduled predose and at post-dose intervals on Days 7 and 14. The record specifies that actual sampling times, rather than scheduled or nominal times, were used in computations that used sampling time. The study dates are listed as 2022-05-09 for start and 2023-05-30 for primary completion. The registry record does not report details of site locations, the randomization ratio, or the reasons for the selected dose groups.
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: The total duration of the study was up to 8 weeks. The Screening Period was up to 4 weeks, Treatment Period was 2 weeks, and safety follow-up phone call was 2 weeks after last study drug administration.
Overall Study
| Stage | Vonoprazan 10 mg QD | Vonoprazan 20 mg QD |
|---|---|---|
| STARTED | 12 | 12 |
| COMPLETED | 12 | 11 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Vonoprazan 10 mg QD | Vonoprazan 20 mg QD |
|---|---|---|
| Miscellaneous | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: PK set: inclusive of all evaluable participants who had at least one measurable concentration result.
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: inclusive of all participants who received at least 1 dose of study drug.
| Characteristic | Unit | Vonoprazan 10 mg QD | Vonoprazan 20 mg QD | Total |
|---|---|---|---|---|
| Participants analysed | 12 | 12 | 24 | |
| Age, Continuous | years | 14.3 (SD 1.78) | 15.2 (SD 1.75) | 14.8 (SD 1.78) |
| Sex: Female, Male: Female | Participants | 6 | 7 | 13 |
| Sex: Female, Male: Male | Participants | 6 | 5 | 11 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 4 | 2 | 6 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 | 10 | 16 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 5 | 8 |
| Race (NIH/OMB): White | Participants | 9 | 7 | 16 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Observed Drug Concentration at Steady State (Cmax-ss) of Vonoprazan, measured over Blood samples were collected predose, once between 0.5 and 2 hours, and once between 2.5 and 4 hours post-dose on Days 7 and 14.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | ng/mL |
| Endpoint classification | not reduced to a single comparison |
Cmax-ss is the maximum observed plasma concentration of a drug at steady state. In this study, it summarizes the highest measured vonoprazan concentration after repeated once-daily dosing, using concentration-time information collected on Days 7 and 14. Concentration is reported in ng/mL. The posted endpoint is a pharmacokinetic measure, not a direct measure of GERD symptoms, quality of life, or clinical benefit.
Concentration measures are useful in a pharmacokinetic study because they describe drug exposure in the body. Comparing descriptive concentration summaries across dose groups can help characterize how observed exposure varied under the study’s dosing conditions. This does not by itself establish a dose-response relationship or show what concentration would be associated with a clinical outcome.
The registry reports the endpoint as a mean with a full range. The 10 mg group has a reported mean of 13.4 ng/mL, with a full range from 6.57 to 25.6. The 20 mg group has a reported mean of 26.7 ng/mL, with a full range from 13.1 to 49.1. A full range describes the lowest and highest observed values in the reported group; it is not a confidence interval and does not quantify uncertainty in the group mean. The registry does not report a confidence interval for either mean.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The reported mean Cmax-ss was 13.4 ng/mL in the vonoprazan 10 mg once-daily group and 26.7 ng/mL in the vonoprazan 20 mg once-daily group. The associated full ranges were 6.57 to 25.6 and 13.1 to 49.1, respectively. These are descriptive results for the pharmacokinetic set, with reported group sizes of 9.0 and 8.0. They describe the observed concentrations in evaluable participants; they are not estimates from all enrolled participants unless those participants were in the endpoint population.
The group means are numerically different, but the registry record does not post a formal inferential comparison, such as a test statistic, p-value, or confidence interval for a between-group contrast. It therefore does not quantify the precision of the difference between the group means or establish whether the observed difference is distinguishable from sampling variation. The full ranges show the spread from the smallest to the largest reported observation in each group. They cannot substitute for uncertainty intervals around the means or for a model-based comparison.
The primary endpoint is a concentration measure. It should be interpreted as evidence about observed pharmacokinetic exposure under the study conditions, not as evidence of symptom improvement, disease control, or comparative clinical effectiveness. Although the study title refers to pharmacodynamics and safety, the primary endpoint presented is pharmacokinetic. The record identifies an adverse-event outcome, but it does not provide a posted clinical efficacy comparison in the results.
The registry’s PK description says the parameters were estimated using a nonlinear mixed effects model and that actual sampling times were used in calculations requiring sampling time. This provides context for how the concentration-time information was handled. The record does not report enough model detail to assess the model specification, diagnostics, covariate handling, or uncertainty estimates. Nor does it report a statistical analysis comparing dose groups. These omissions limit how far the reported summaries can support claims beyond description.
The recorded total enrollment is 24, whereas the endpoint group sizes are 9.0 and 8.0. The endpoint description makes clear that the PK set includes evaluable participants with at least one measurable concentration result. The registry record does not explain why the endpoint group sizes differ from overall enrollment, so the difference should not be interpreted as a particular pattern of missingness, exclusion, or withdrawal. The record also does not explain whether the observed ranges reflect all scheduled concentrations or the participant-level Cmax-ss estimates; the endpoint description identifies the parameters as estimated from concentration-time data.
Overall, the posted results provide dose-group descriptive estimates of maximum observed steady-state concentration, with a full range for each group. They do not report a formal dose comparison or establish clinical consequences of the concentrations. Any interpretation beyond the measured pharmacokinetic profile would require evidence not reported in the registry record.
9. Statistical Methods Explained
What does the endpoint summarize?
Cmax-ss combines two ideas. Cmax refers to a maximum concentration, while ss indicates steady state: the concentration pattern after repeated dosing has reached a stable pattern. The endpoint is therefore a pharmacokinetic summary of the maximum observed plasma concentration under repeated dosing, rather than a measure of a participant’s symptoms or a direct treatment outcome.
The registry reports this endpoint as a mean and full range. A mean describes the average of the participant-level values included in the summary. A full range reports the lowest and highest observed values. It conveys the span of the observed data but says little about the shape of the values between those endpoints. A range is also different from a confidence interval: a confidence interval expresses uncertainty about an estimate, while a full range describes observed values. No confidence interval for the means is reported in the registry record.
How were concentration data handled?
The registry says plasma pharmacokinetic parameters were estimated using a nonlinear mixed effects model. In general, this class of model can represent concentration-time patterns while accounting for repeated measurements and variation across participants. The registry does not report the specific model structure, parameterization, diagnostics, or estimation details, so those aspects cannot be evaluated from the record.
Sampling times were specified around dosing on Days 7 and 14: predose, once between 0.5 and 2 hours after dosing, and once between 2.5 and 4 hours after dosing. The record says actual sampling times, rather than scheduled or nominal times, were used in computations involving sampling time. In general, using actual times can represent when measurements were truly collected instead of assuming they occurred exactly at their planned times. The record does not describe how samples outside the scheduled windows, if any, were handled.
The primary endpoint population was the PK set: evaluable participants with at least one measurable concentration result. This definition ties the summary to participants with usable concentration information, not automatically to every enrolled participant. The endpoint group sizes are 9.0 for 10 mg and 8.0 for 20 mg. The record does not report participant-level exclusions, reasons for non-evaluability, or the amount and handling of missing concentration data.
What does randomization contribute?
Random assignment can, in general, reduce systematic differences between groups at baseline, because assignment is not based on participant characteristics. It does not guarantee that groups will be identical, especially in a study with limited endpoint group sizes. The registry identifies the study as randomized and parallel-group, but does not report the allocation procedure, allocation ratio, or information on baseline balance. The open-label designation means masking is listed as none. The record does not describe any measures to reduce bias in concentration measurement or analysis.
What can be inferred from the summaries?
The reported means and ranges are descriptive. The 10 mg group mean is 13.4 ng/mL, with a full range of 6.57 to 25.6; the 20 mg group mean is 26.7 ng/mL, with a full range of 13.1 to 49.1. Descriptive statistics show what was observed in the recorded analysis population. They do not, on their own, supply a standard error, confidence interval, hypothesis test, or estimate of uncertainty for a difference between groups.
In general, a confidence interval gives a range of values compatible with the data under a specified statistical procedure and assumptions. It can communicate uncertainty in an estimate, but it is not the same as the range of individual observations. The registry record does not report confidence intervals for the endpoint means or a formal inferential contrast between doses. No p-value for the primary endpoint is reported.
Why can over-dispersion matter in general?
Over-dispersion refers generally to observed variability greater than a statistical model’s assumptions would anticipate. When it occurs, standard errors and tests from a model that does not account for it can be too optimistic. This concept is relevant to statistical modeling broadly, but the endpoint is described through a nonlinear mixed effects model, and the registry does not report whether over-dispersion was assessed or how model fit was evaluated. It would not be appropriate to infer that over-dispersion occurred or that it affected these results.
How should planning illustrations be understood?
The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. In general, such an illustration asks how many participants per arm might be needed to detect an effect under stated assumptions. It is a prospective planning exercise, not a measure of the study’s observed ability to detect an effect. The assumptions are not a report of the trial’s original design or statistical plan, and the registry record does not report a sample-size justification for the trial. No planning figure should be treated as observed power.
For this study, the registry record does not report a posted inferential analysis of the primary endpoint. The planning assumptions therefore cannot be used to fill in missing evidence about the precision or statistical significance of the observed dose-group summaries. A formal comparison would require a defined estimand, analysis method, and uncertainty measure; these are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists five outcome measures, while one secondary outcome is identified in the posted results: the number of participants experiencing adverse events. The primary endpoint is Cmax-ss. The record does not report a multiplicity strategy, such as an adjustment for testing multiple outcomes or a hierarchy for interpreting them. Because no inferential analyses are posted for the primary endpoint, the record also does not show how multiplicity might have affected conclusions about that endpoint.
The endpoint population is the PK set, defined as evaluable participants with at least one measurable concentration result. The reported PK group sizes are 9.0 for 10 mg and 8.0 for 20 mg. Overall enrollment is 24. The registry record does not report the reasons that the endpoint group sizes differ from enrollment, the number or pattern of missing samples, or the handling of missing concentration measurements. It is therefore not possible to determine from this record whether missing data were related to participant characteristics, dose, or observed concentrations.
The record does not report imputation methods, sensitivity analyses, or a detailed analysis population definition beyond the PK-set description. It also does not report whether any participants were excluded after randomization or how deviations from scheduled dosing or sampling were addressed. These details matter because analyses restricted to evaluable participants can describe the observed PK data but may not represent all enrolled participants if evaluability is related to measured outcomes.
No formal analysis results are posted for the listed outcomes in the registry record. The record does not report a statistical analysis plan, interim analyses, or procedures for handling multiple comparisons. Those features should not be inferred from the study’s Phase 1 designation or its randomized design.
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 |
|---|---|---|---|
| Vonoprazan 10 mg QD | 0 | 12 | 0.0% |
| Vonoprazan 20 mg QD | 0 | 12 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Vonoprazan 10 mg QD | 0 of 12 |
| Vonoprazan 20 mg QD | 0 of 12 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Vonoprazan 10 mg QD | 4 of 12 |
| Vonoprazan 20 mg QD | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Vonoprazan 10 mg QD | Vonoprazan 20 mg QD |
|---|---|---|---|
| Cellulitis | Infections and infestations | 1 of 12 | 0 of 12 |
| Enterocolitis infectious | Infections and infestations | 0 of 12 | 1 of 12 |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | 1 of 12 | 0 of 12 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 12 | 0 of 12 |
| Migraine | Nervous system disorders | 1 of 12 | 0 of 12 |
| Anxiety | Psychiatric disorders | 1 of 12 | 0 of 12 |
The registry separates serious adverse events from other adverse events. For serious adverse events, the posted counts are 0 among 12 participants at risk in the vonoprazan 10 mg group and 0 among 12 participants at risk in the vonoprazan 20 mg group. Deaths are reported as 0 in both groups. These are recorded counts within the safety population described for each group; they do not establish that an event is impossible or that risk is absent.
For other adverse events, the record reports 4 among 12 at risk in the 10 mg group and 1 among 12 at risk in the 20 mg group. The registry record does not provide further details in the listed summary about event types, timing, severity, relatedness, or participant-level recurrence. Those counts should not be read as a formal comparison between doses. A zero count in the serious-event category does not show that the groups have identical safety profiles, and differences in observed counts do not establish a causal dose effect.
The safety counts use the stated at-risk populations, while the pharmacokinetic summaries use the PK set. These are distinct analysis descriptions in the registry record. Safety counts and PK endpoint group sizes should not be combined or treated as if they refer to the same population definition.
12. What the Result Does, and Does Not, Mean
The results do show that the registry reports measurable vonoprazan concentration summaries for both dose groups in adolescents with symptomatic GERD. Mean Cmax-ss was 13.4 ng/mL for 10 mg once daily and 26.7 ng/mL for 20 mg once daily. The corresponding full ranges were 6.57 to 25.6 and 13.1 to 49.1. These statistics describe the observed pharmacokinetic endpoint in the evaluable PK population.
The results do not, as posted, quantify a formal contrast between dose groups. The registry record does not provide a test, p-value, confidence interval for a contrast, or other inferential result for Cmax-ss. The means are numerically different, but descriptive differences alone do not establish the precision of a contrast or determine whether it is compatible with chance variation. Full ranges describe the observed extremes and should not be interpreted as uncertainty intervals for the means.
The endpoint also does not establish a clinical effect. Cmax-ss is a concentration measure, not a symptom, disease-control, or patient-reported outcome. The study title includes pharmacodynamics and safety, but the posted primary result described in the registry is pharmacokinetic. The record identifies an adverse-event outcome, yet the available counts do not establish a comparative safety effect.
The results apply to the study population and analysis definitions recorded in the registry. The PK set includes evaluable participants with at least one measurable concentration result, and its group sizes are 9.0 and 8.0. The record does not explain the difference from overall enrollment or provide enough information to assess how non-evaluable participants may affect interpretation. The findings should therefore be understood as descriptive observations in the reported PK set, rather than as a complete account of outcomes for all enrolled participants or a basis for conclusions beyond the recorded endpoints.
13. Why This Trial Matters Statistically
This study is statistically informative because it focuses on pharmacokinetic measurement in adolescents, a population identified in the registry as having symptomatic GERD. Concentration-time data and Cmax-ss summaries can describe drug exposure under repeated dosing conditions. The record reports results separately for the 10 mg and 20 mg once-daily groups, making the dose-specific summaries visible without presenting them as clinical outcome comparisons.
The endpoint also illustrates why a summary statistic needs context. A mean conveys a group average, while a full range shows the observed extremes. Neither alone communicates the uncertainty around the mean or a between-group effect. The registry’s lack of a posted inferential comparison matters: readers can describe the reported concentrations, but cannot use the record to assess the precision of a dose contrast through a reported confidence interval or test.
The distinction between the PK set and the safety at-risk populations is another important statistical feature. Different outcomes can have different analysis populations, and their denominators should be interpreted according to their definitions. Here, the PK summaries use evaluable participants with at least one measurable concentration result, while safety counts are reported against the stated at-risk groups.
Finally, the study shows the limits of registry-level reporting. The record identifies a nonlinear mixed effects approach and specifies use of actual sampling times, but does not report model details, diagnostics, or a full statistical analysis plan. That information would be needed to evaluate modeling choices and inferential procedures. The study’s value in this record is therefore primarily descriptive: it documents concentration summaries and safety counts without resolving broader clinical questions.
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 gives limited detail for assessing the primary pharmacokinetic analysis. It identifies a nonlinear mixed effects model but does not report the model structure, parameter estimates beyond the posted endpoint summaries, diagnostics, or uncertainty estimates. The record does not report a confidence interval or inferential comparison for the dose groups. As a result, the precision of the group means and the uncertainty around a dose contrast cannot be evaluated from the posted results.
The PK set includes evaluable participants with at least one measurable concentration result. Its reported group sizes are 9.0 and 8.0, while overall enrollment is 24. The registry record does not account for the difference or describe missing samples, non-evaluable participants, withdrawals, or exclusions. The effect of any missing or unavailable concentration data is therefore unknown.
The sampling schedule is described, and actual sampling times were used in calculations involving time. However, the record does not describe adherence to the schedule, handling of samples outside the specified windows, or whether concentrations were available at all scheduled times. It also does not provide participant-level concentration-time data, which limits independent assessment of variability and model fit.
The study was open-label, and the registry lists masking as none. For an objectively measured concentration endpoint, the implications may differ from those for a subjective outcome, but the record does not report safeguards against measurement or analysis bias. Randomization is recorded, but details of the allocation procedure are not reported. The registry also does not provide a sample-size justification, a detailed statistical analysis plan, or a multiplicity strategy. These omissions constrain assessment of both design and interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of Vonoprazan in Adolescents With Symptomatic Gastroesophageal Reflux Disease — NCT05343364.
- Registry record last updated 2025-04-23; status last verified 2025-04.
- Results first posted 2024-06-03.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes a completed Phase 1 randomized, parallel-group, open-label, multicenter study of vonoprazan in adolescents with symptomatic GERD. Enrollment was 24. Participants received vonoprazan 10 mg or 20 mg once daily for 14 days. The primary objective was pharmacokinetic evaluation, with maximum observed concentration at steady state (Cmax-ss) as the posted primary endpoint.
The mean Cmax-ss was 13.4 ng/mL, with a full range of 6.57 to 25.6, in the 10 mg group; in the 20 mg group, the mean was 26.7 ng/mL, with a full range of 13.1 to 49.1. The PK set group sizes were 9.0 and 8.0. The registry does not report an inferential comparison of these summaries. It also reports 0 serious adverse events in each safety group and other adverse events among 4 participants in the 10 mg group and 1 participant in the 20 mg group. The record does not provide enough detail to assess missing concentration data or the full statistical analysis.