A Study to Assess the Effect of Verinurad on the Electric Activity of the Heart: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Effect of Verinurad on the Electric Activity of the Heart (NCT04256629), a randomized phase 1 study. The primary outcome is Model Predicted Baseline-corrected and Placebo-corrected QT Interval Corrected for Heart Rate (HR) Using Fridericia's Formula (QTcF)(ΔΔQTcF) (Derived From Concentration-QTcF Analysis) at Geometric Mean of Cmax of Verinurad.

2. Clinical Question

The registry frames the investigation as an assessment of verinurad’s effect on ECG measurements, with particular focus on the QT/QTc interval. The posted primary estimates concern QTcF, not every ECG interval. Other outcomes listed include changes in heart rate, RR, PR and QRS intervals. The record does not report results for those outcomes in the registry record.

3. Trial Design

This was a completed, single-centre, randomized, triple-masked, placebo-controlled Phase I crossover study. The registry reports enrollment of 24 healthy volunteers. Participants were assigned to one of six treatment sequences, each of which included the three treatments in a different order. Each participant was scheduled to receive all three treatments as single doses, with wash-out periods of at least 7 days between study-dose administrations.

The crossover structure means that treatment comparisons can use measurements from the same participant under different treatment conditions. This can account for stable differences between individuals, but it also makes the timing and ordering of treatments relevant to interpretation. The record describes the sequence structure and wash-out interval; it does not report further details about how period or sequence effects were handled in the primary model.

The study compared two verinurad regimens, each combined with allopurinol 300 mg, against placebo. The record describes the regimens as a 24 mg ER8 formulation and a 40 mg IR formulation, while the posted primary results are labeled Treatment A and Treatment B. A mapping from those arm labels to the regimens is not reported in the registry record, so the estimates should be interpreted by their posted treatment labels rather than assigned to a specific formulation.

The study began on 2020-03-03, reached primary completion on 2020-08-21 and is listed as completed. The primary outcome is a model-derived QTcF estimate at the geometric mean of verinurad Cmax. This endpoint is distinct from a direct treatment-group mean at a single scheduled timepoint. The registry says that the primary analysis summarizes measurements across the listed timepoints using a linear mixed-effect concentration-QTcF model.

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 study consisted of a Screening Period of maximum 28 days. There were wash-out periods of at least 7 days between each study dose administration. The assessments were done as per the schedule of assessment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: In the Primary Outcome we present the predicted value of ΔΔQTcF based on a statistical model created for the study. The results may be presented for the active arms only, since the placebo arm did not receive Verinurad and thus have no Cmax. Placebo-corrected and baseline adjusted QTcF, ∆∆QTcF with 90% confidence interval at the verinurad maximum concentration of interest is presented as the primary result from the analysis.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Model Predicted Baseline-corrected and Placebo-corrected QT Interval Corrected for Heart Rate (HR) Using Fridericia's Formula (QTcF)(ΔΔQTcF) (Derived From Concentration-QTcF Analysis) at Geometric Mean of Cmax of Verinurad, measured over Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose.

The primary endpoint is the model-predicted baseline-corrected and placebo-corrected change in QTcF, denoted ΔΔQTcF, at the geometric mean of verinurad Cmax. QTcF is the QT interval corrected for heart rate using Fridericia’s formula. The unit is milliseconds, and uncertainty is reported using a 90% confidence interval.

QTcF is used in this study as an ECG measure for examining how treatment exposure relates to cardiac electrical activity. Correcting the QT interval for heart rate helps make measurements more comparable when heart rates differ. Baseline correction accounts for the participant’s baseline measurement, while placebo correction expresses the estimated change relative to the placebo condition. These corrections define the endpoint; they do not make the result a direct measurement of an individual participant’s change.

The estimate is derived from a concentration-QTcF analysis. As described in the registry, it is a model result summarizing data across the scheduled measurements, not a separate observed value for every timepoint. The listed assessment schedule extends from baseline through 48 h post-dose. The registry also states that placebo does not have a verinurad Cmax, so the reported active-treatment values are placebo-corrected model estimates rather than separate placebo values at that exposure.

The endpoint is therefore useful for describing the estimated relationship between verinurad exposure and QTcF under the study conditions. It does not by itself describe all ECG effects or provide a participant-level account of the observed measurements.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome uses a linear mixed-effect concentration-QTcF model. In general, concentration-response models relate measured drug concentration to an outcome, here QTcF, while accounting for the repeated measurements and structure of the study. A mixed-effect model can represent both systematic relationships and variation among participants. The registry identifies the model type but does not report its full equation, covariates, assumptions, estimation details or diagnostic checks.

What does baseline correction mean?

Baseline correction expresses a post-dose measurement relative to a baseline measurement. In this trial, the primary endpoint is also placebo-corrected, so the model result represents a baseline-adjusted change relative to placebo. This differs from reporting the raw QTcF value in an active-treatment arm. Baseline and placebo correction define the contrast being estimated; they do not eliminate uncertainty or guarantee that all sources of bias have been removed.

Why model concentration and QTcF together?

The study describes measurements at baseline and multiple post-dose times on Day 1, Day 2 and Day 3. A concentration-QTcF model uses the relationship between drug exposure and QTcF across measurements to estimate the endpoint at a specified exposure. Here, that exposure is the geometric mean of Cmax. The registry explicitly notes that the model yields one set of numbers summarizing the measurements across timepoints, rather than a value for each scheduled time.

This approach is different from comparing treatment means at a single hour. It can use measurements collected at different concentrations and times to estimate an exposure-linked QTcF change. Its interpretation depends on the model representing that relationship adequately. The registry record does not report model-fit diagnostics, the handling of departures from the assumed relationship, or sensitivity analyses.

What does the crossover design contribute?

In a crossover study, participants receive multiple treatments in sequence. A participant can therefore contribute measurements under more than one treatment condition. In general, this can reduce the influence of stable between-person differences in a treatment comparison. It also means that period, sequence and carryover effects may matter. The record reports six treatment sequences and wash-out periods of at least 7 days, but the details of how the model addressed period, sequence or carryover are not reported in the registry record.

The mixed-effect model is consistent with analysis of repeated measurements, but the available description does not establish which random effects or within-person correlation structures were used. Those details should not be inferred from the model name alone. Nor does the record describe the exact concentration sampling schedule or the method used to derive individual or geometric mean Cmax values.

How should the confidence intervals be read?

The posted intervals are 90% confidence intervals. In general, a confidence interval communicates statistical uncertainty around an estimate under the model and analysis assumptions. A narrower interval indicates greater precision than a wider interval on the same scale, but the interval does not measure clinical importance and cannot identify sources of bias. The intervals in this study should be read alongside the model-derived nature of the endpoint and the limitations in the registry description.

The treatment estimates are reported in milliseconds. The confidence interval for Treatment A runs from -4.7 to -0.9, while the interval for Treatment B runs from -3.1 to 2.5. Those endpoints are reported as posted; no additional calculation is required to describe whether zero falls inside an interval. The record does not provide a p-value for these estimates, and an interval should not be converted into an unreported test result.

What is not described?

The registry record does not report the full statistical analysis plan, the model specification, the sample-size justification, planned interim analyses, or details of any multiplicity adjustment. It also does not report how missing measurements were handled, the precise analysis population, or model diagnostics. Such details affect how the estimates can be evaluated and reproduced. Their absence in the registry record does not establish that no such procedures were used; it means they are not described in the record.

The study also has secondary outcomes covering heart rate and RR, PR and QRS intervals. Those outcomes are distinct from the primary concentration-QTcF endpoint. The registry entries described for this analysis do not include numerical results for those secondary outcomes, and the primary estimates should not be generalized to them.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists secondary outcomes for baseline-corrected and placebo-adjusted measures of heart rate, RR interval, PR interval and QRS interval. The primary outcome is a separate model-derived QTcF measure. When a study evaluates multiple outcomes or treatment contrasts, multiplicity can affect the chance of obtaining at least one apparently notable result by chance. In general, trial analyses may address this through a prespecified hierarchy, adjustment procedure or other strategy. The multiplicity strategy for this trial is not reported in the registry record.

The record does not report whether interim analyses were planned or conducted, nor does it describe a sample-size justification. Those items should not be inferred from the trial’s enrollment or the posted outcome estimates. Any sample-size illustrations accompanying the results are planning calculations, not observed power and not evidence of the trial’s original design rationale.

The registry describes 24 enrolled participants and reports 24 participants for each of the two primary result arms. Safety denominators vary by treatment group: 22 for Treatment A, 24 for Treatment B and 23 for Treatment C. These differing counts do not by themselves explain why the denominators differ or establish how missing outcome measurements were handled. The registry record does not report the analysis population definition, participant flow by outcome, reasons for missing measurements, or a missing-data method for the primary model.

In a crossover study, missing measurements may affect the amount of within-participant information available across treatment periods. In general, the consequences depend on which periods or measurements are missing and on the analysis assumptions. The registry information does not permit those features to be assessed. The record also does not report whether sensitivity analyses were conducted to examine the effect of missingness.

11. 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 serious adverse event counts are zero in each of the three treatment groups. The corresponding numbers at risk are 22 for Treatment A, 24 for Treatment B and 23 for Treatment C. No deaths are reported in any group. These are counts within the registry’s reported safety groups; they are not the primary QTcF efficacy estimates.

A zero count means that no serious adverse events were recorded among the participants included in that group’s reported denominator. It does not establish that the risk is absent, and it does not describe the precision of an underlying event rate. The denominators are limited, and the registry record does not report further detail about event monitoring or the criteria used for attribution.

The record also lists other, non-serious adverse events affecting 8 participants in Treatment A, 4 in Treatment B and 5 in Treatment C. These counts are separate from serious adverse events. No serious adverse event terms are listed among the top serious terms. The adverse-event counts should be interpreted as descriptive registry results, not as a comparison proving that one treatment is safer than another.

The treatment groups’ safety denominators differ. The registry record does not explain those differences, so the counts should not be converted into a comparative claim without further information. The study’s healthy-volunteer population and single-dose setting also define the context of these observations.

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

The primary results describe model-predicted, baseline-corrected and placebo-corrected QTcF estimates for Treatment A and Treatment B at the geometric mean of verinurad Cmax. Treatment A has an estimate of -2.8 msec with a 90% confidence interval from -4.7 to -0.9. Treatment B has an estimate of -0.3 msec with a 90% confidence interval from -3.1 to 2.5. These are not raw readings or timepoint-specific treatment means.

The intervals express uncertainty under the statistical model. They do not establish the complete range of possible effects, account for every source of bias, or indicate whether the magnitude is clinically important. The registry does not provide a decision threshold or p-value alongside the estimates. The results therefore describe the model’s estimates and precision, rather than a complete record of the sponsor’s statistical decision process.

The record describes two verinurad regimens, but it does not link the Treatment A and Treatment B labels to the 24 mg ER8 and 40 mg IR formulations. The estimates cannot be assigned to a specific regimen from these labels alone. The placebo-corrected result is also not a direct placebo value at Cmax: the registry notes that placebo participants do not receive verinurad and therefore have no verinurad Cmax.

This study enrolled healthy volunteers. Although chronic kidney disease is identified as the intended indication, the results do not directly describe measurements in people with chronic kidney disease. The single-dose, crossover setting also does not establish what would be observed under repeated dosing or in other populations.

In short, the posted results provide a focused statistical description of a modeled ECG endpoint under the trial conditions. They do not answer every question about ECG outcomes, adverse events, longer-term use or other populations. Those questions require evidence not reported in this registry record.

13. Why This Trial Matters Statistically

This trial illustrates how a clinical study can target a specific measurement and exposure relationship rather than relying only on an overall average at a fixed time. The primary outcome uses concentration-QTcF modeling to estimate a placebo-corrected QTcF change at the geometric mean of verinurad Cmax. That makes the endpoint a model summary across measurements, and interpretation depends on recognizing that it is not a direct value observed at one timepoint.

The crossover design is also statistically important. Each participant was scheduled to receive all three treatments in an assigned sequence. In general, within-participant comparisons can account for stable differences between people, while requiring attention to treatment order, period effects and possible carryover. The registry describes the sequences and wash-out periods, but does not report the model details needed to assess how those design features entered the analysis.

The two posted primary estimates have different confidence-interval patterns: the interval for Treatment A is entirely below zero, while the interval for Treatment B includes zero. This emphasizes why estimates and uncertainty should be considered together, rather than relying on a point estimate alone. The registry record does not provide a p-value or a decision rule, and the labels are not mapped to specific dose formulations.

Finally, the study shows the importance of separating outcome types and populations. The primary QTcF model result is not interchangeable with results for other ECG intervals or with the safety counts. Nor do results in healthy volunteers directly represent people with the intended indication. These distinctions are central to reading the numerical evidence accurately.

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 principal endpoint is a model-derived concentration-QTcF estimate, not a collection of direct arm-level QTcF values at Cmax. The registry explicitly says that non-placebo-corrected QTcF data values were not collected or could not be obtained for each arm at that exposure. The interpretation consequently depends on the model’s relationship between concentration and QTcF across the scheduled measurements.

The registry describes the model as linear mixed-effect but does not report its full specification, covariates, random-effects structure, assumptions, diagnostics or sensitivity analyses. Details on handling period, sequence and carryover effects are also not reported, despite the crossover design. The registry record does not report how missing measurements were treated or give reasons for the differing safety denominators.

Treatment A and Treatment B are not mapped in the posted arm results to the named 24 mg ER8 and 40 mg IR regimens. This limits regimen-specific interpretation. The record also does not report the statistical decision threshold, multiplicity strategy, sample-size justification or planned interim analyses. These omissions limit assessment of the analysis plan and its operating assumptions.

The study enrolled healthy volunteers and assessed single-dose treatments. Its findings therefore have a defined population and dosing context. The intended indication is chronic kidney disease, but the enrolled population does not provide direct evidence in that group. The registry’s primary estimates also do not provide numerical results for the other ECG outcomes listed as secondary measures.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Assess the Effect of Verinurad on the Electric Activity of the Heart — NCT04256629.
• Registry record last updated 2022-01-31; status last verified 2021-11.
• Results first posted 2022-01-31.
• 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.

18. Record Summary

NCT04256629 is a completed, single-centre, randomized, triple-masked, placebo-controlled, three-period crossover Phase I study in healthy volunteers, with enrollment of 24. Participants were assigned to treatment sequences including two single-dose verinurad regimens with allopurinol 300 mg and placebo, with wash-out periods of at least 7 days.

The primary outcome was a model-predicted, baseline-corrected and placebo-corrected QTcF change at the geometric mean of verinurad Cmax, reported in milliseconds with 90% confidence intervals. Treatment A was -2.8 msec (90% confidence interval -4.7 to -0.9); Treatment B was -0.3 msec (90% confidence interval -3.1 to 2.5). The registry does not map those labels to the named dose formulations.

Serious adverse event counts and deaths were zero in all three safety groups. The study began on 2020-03-03, reached primary completion on 2020-08-21 and is listed as completed.