A Study of Valcyte (Valganciclovir) Syrup Formulation in Pediatric Solid Organ Transplant Recipients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Valcyte (Valganciclovir) Syrup Formulation in Pediatric Solid Organ Transplant Recipients (NCT00090766), a non-randomized phase 2, phase 3 study. The primary outcome is Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir.

2. Clinical Question

The study’s stated focus was the safety and pharmacokinetics of a valganciclovir syrup formulation in pediatric solid organ transplant recipients. The registry lists valganciclovir as the intervention and describes oral solution or tablets in the age-group regimens. It does not report a comparison of syrup against another formulation or against no treatment.

The primary endpoint is a concentration-based measure, rather than a direct comparison of clinical outcomes. The registry also identifies secondary outcomes concerning cytomegalovirus disease, treatment failure, graft loss, drug concentrations and elimination half-life, and episodes of rejection. Numerical results for these outcomes are not reported in the registry record.

The study enrolled 63 participants, but the primary endpoint population is described in terms of participants from three named studies who completed specified treatment and had a plasma sample. The record does not establish that the primary pharmacokinetic population is identical to the enrollment group. It also notes that one participant was not analyzed for the primary endpoint after both a kidney and liver transplant. These details matter when interpreting who contributed to the pharmacokinetic measure.

3. Trial Design

The registry classifies the study as Phase 2 and Phase 3, non-randomized, unmasked and single-group. Enrollment was 63, and the study status is completed. Its recorded start was 2004-05 and primary completion was 2005-05. The stated aim was to assess safety and pharmacokinetics in pediatric solid organ transplant recipients.

There is no randomized control group in the design description. The three treatment groups are categorized by age: 2 years or younger, older than 2 and younger than 12 years, and 12 years or older. These categories describe the valganciclovir regimen groups, not like-for-like randomized comparisons. Differences between age groups could reflect age or other characteristics, and the registry design does not support attributing such differences to treatment.

For each age group, the description specifies oral solution or tablets, treatment from the time of kidney transplantation, and treatment for up to 100 days after transplantation. The maximum daily dose is 900 mg. The listed dose formula is 7 multiplied by body surface area and creatinine clearance. The record does not report further details about dose adjustments or adherence.

The primary endpoint is a mean area under the plasma concentration-time curve from 0 to 24 hours. Sampling is described as pre-dose and at 1-3, 3-7 and 7-12 hours after dosing on a day between Day 7 and Day 14, with additional time points at Week 6, Week 10 and Week 14. A compartmental model was used to measure plasma concentrations.

The primary endpoint population is described as participants in studies WP16296, WP16303 and WV16726 who completed the specified treatment and had at least one plasma sample. The registry does not report the rationale for this population definition or a protocol-level explanation for combining these studies. It also does not report a control-group design, randomization procedures, masking procedures or a sample-size justification.

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: Participants were screened within 48 hours prior to transplant surgery (Day 1) and received valganciclovir from Day 1.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) population comprised of all participants from studies WP16296, WP16303 and WV16726 who had completed the specified treatment and from whom at least one plasma sample was taken. Here n represents number of participant with specific transplant i.e., kidney, liver, and heart.

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 population included all participants who received at least one dose of valganciclovir

6. Primary Endpoint

The registry lists the primary outcome as Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir, measured over Pre-dose; 1-3, 3-7, 7-12 hours post dose on any day between Day 7 to Day 14; Week 6, Week 10, and Week 14.

The primary endpoint is the mean area under the plasma concentration-time curve from time zero through 24 hours after valganciclovir dosing, expressed in mcg*hr/mL. AUC represents drug concentration in plasma accumulated over time. It summarizes exposure across the stated time interval rather than describing concentration at just one sampling point.

In general, pharmacokinetic measures are used to characterize how drug concentrations change in the body after dosing. AUC is useful because exposure can be informed by multiple concentration measurements over time. The registry states that a compartmental model was used to measure valganciclovir plasma concentrations. Such a model provides a framework for relating sampled concentrations to a concentration-time profile; the model details and estimation procedures are not reported in the registry record.

The endpoint is reported as a mean with standard deviation as the stated dispersion measure. A mean describes the average value in the analyzed population, while a standard deviation describes the spread of individual values around that average. Neither measure alone gives the uncertainty around the estimated mean; that would generally require an inferential estimate such as a confidence interval.

The registry specifies the planned assessment times: pre-dose and several post-dose sampling intervals on a day between Day 7 and Day 14, followed by assessments at Week 6, Week 10 and Week 14. It does not report the numerical AUC means, standard deviations, confidence intervals or statistical comparisons. Therefore, the endpoint’s magnitude and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as a mean, with standard deviation, for a continuous pharmacokinetic outcome. A continuous outcome can take values along a measurement scale rather than being a count of people in categories. Here the scale is mcg*hr/mL and the measure is area under the plasma concentration-time curve from time zero to 24 hours.

What does the mean describe?

In general, a mean is the arithmetic average of observed measurements in the analysis population. It gives a central summary, but does not describe how similar or different individual measurements are. The registry record does not report the numerical mean for this endpoint, so its value cannot be interpreted.

What does the standard deviation describe?

In general, the standard deviation summarizes dispersion of measurements around the mean. A larger standard deviation indicates more spread in the measured values, while a smaller one indicates values closer to the mean. It is not the same as a confidence interval: the standard deviation describes variation among observations, whereas a confidence interval describes uncertainty in an estimated quantity. The registry names standard deviation as the dispersion measure but does not report its numerical value.

How does the sampling schedule relate to AUC?

The study collected or planned plasma measurements at pre-dose and specified post-dose times, including sampling on a day between Day 7 and Day 14 and later assessments at Week 6, Week 10 and Week 14. AUC integrates concentration over the stated interval, so it depends on the concentration-time profile, not just one sample. The registry says a compartmental model was used. In general, a compartmental model represents concentration changes using a specified mathematical structure and estimates a profile from observed samples. The record does not describe the model structure, fitting method, handling of values below measurement limits or diagnostics of model fit.

What does a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data under the statistical procedure used. Its width conveys precision: a narrower interval indicates greater precision, and a wider interval indicates greater uncertainty. The registry record does not report a confidence interval for the primary endpoint. Without an estimate and its uncertainty, readers cannot gauge how precisely the mean AUC was estimated.

What can be inferred from this design?

The study is non-randomized and single-group. In general, random assignment can help balance measured and unmeasured characteristics between treatment groups, whereas a single-group study does not provide that randomized comparison. The age-group categories are not randomized arms. They can describe regimen and safety information by age, but comparisons across them may reflect differences between the groups beyond age or dosing. The registry does not report adjusted comparisons that address such differences.

There is no separate comparator described in the record. Accordingly, a within-study contrast against a concurrent untreated or alternative-treatment group is not available from the design description. The registry does not report a comparative estimate for the primary pharmacokinetic endpoint.

Why does over-dispersion matter?

In general, over-dispersion occurs when the variability in data exceeds what a statistical model assumes. It is particularly relevant to count outcomes when a simple model assumes a particular relationship between the mean and variance. If over-dispersion is ignored, uncertainty estimates can be too small and inferential conclusions can be overly confident. This study includes count-based safety and clinical outcomes among its listed measures, but the registry does not report a model for those outcomes or whether over-dispersion was assessed. This is a general statistical consideration, not a claim about the analyses used in this study.

What is not available about the analysis?

The registry record does not report a detailed statistical analysis plan, the calculation method for the primary endpoint, assumptions for the pharmacokinetic model, a missing-data method, or a method for adjusting for multiple outcomes. It does not report numerical primary results or inferential analyses. Therefore, the method description supports an explanation of the endpoint and its intended summary, but not a reconstruction of the analysis or an independent verification of the result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and identifies secondary outcomes concerning cytomegalovirus disease over time, treatment failures, graft loss, maximum plasma concentration, elimination half-life and rejection episodes over time. The record does not report how many hypotheses were tested, which outcomes were treated as confirmatory, or whether any adjustment for multiple comparisons was planned or used. It also does not report an analysis plan that would clarify the order or priority of the outcomes.

In general, testing multiple outcomes can increase the chance of finding an apparently notable result by chance. Multiplicity methods are used to control or describe this issue, depending on the study’s objectives. No such method is reported in the registry record, so it is not possible to determine how multiplicity was handled.

The primary pharmacokinetic population is defined as participants from studies WP16296, WP16303 and WV16726 who completed specified treatment and had at least one plasma sample. The record notes that one participant was not analyzed for the primary outcome after both a kidney and liver transplant. It does not report the number of participants contributing to each analysis, the reasons for any other missing observations, or a method for handling missing measurements.

In general, missing data can affect both the estimated result and its precision, particularly if missingness is related to participant characteristics or outcomes. The registry does not provide enough detail to assess whether missingness was minimal, balanced across groups or addressed with a particular statistical method. The broader population definition also means the relationship between overall enrollment and the primary pharmacokinetic analysis group is not fully documented. These limitations restrict assessment of both representativeness and robustness.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: transplant rejection (12.0%), anaemia (11.8%), pyrexia (9.5%), intra-abdominal haemorrhage (9.5%), cytomegalovirus viraemia (9.5%).

The registry reports serious adverse-event counts in three age categories. In the group aged 2 years or younger, 13 of 17 participants were recorded as affected by a serious adverse event. In the group older than 2 and younger than 12 years, 11 of 21 were affected. In the group aged 12 years or older, 11 of 25 were affected. These are descriptive counts within the recorded groups, not comparisons against a control group.

The registry also lists serious-event terms with percentages: transplant rejection, 12.0%; anaemia, 11.8%; pyrexia, 9.5%; intra-abdominal haemorrhage, 9.5%; cytomegalovirus viraemia, 9.5%; and subdural haematoma, 5.9%. The record does not explain the denominator for each percentage in the details, so these percentages should be read as posted rather than recalculated or directly compared across terms.

Serious adverse events should not be assumed to have been caused by the study treatment. The registry does not report event attribution in the listed figures, nor does it give timing, duration or a comparison group for these events. Death counts are not reported in the registry record.

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

The registry record establishes that the study was designed to assess valganciclovir safety and pharmacokinetics in pediatric solid organ transplant recipients. It defines a primary exposure measure, gives a dosing description by age category and specifies a plasma sampling schedule. It also lists clinical and safety outcomes of interest.

However, the record does not report the numerical primary endpoint results. There is no posted mean AUC or standard deviation from which to describe the observed exposure or its variability. Nor is a confidence interval reported to show precision. The study’s primary pharmacokinetic finding therefore cannot be characterized from the registry record.

The serious adverse-event counts and listed terms provide descriptive safety information, but not a causal estimate. The study is non-randomized and single-group, and no separate comparator is described. The recorded age groups are not randomized arms. Counts or percentages across these groups cannot establish whether treatment caused an event or whether one age group had a treatment-related risk different from another.

The named secondary outcomes include clinical events and additional pharmacokinetic measures. Their numerical results are not reported in the registry record. The record therefore does not support conclusions about the frequency of cytomegalovirus disease, treatment failure, graft loss, rejection, maximum concentration or elimination half-life.

In general, a study can provide useful information about measurement procedures and observed events without establishing a comparative treatment effect. For this record, the appropriate interpretation is limited: the study’s design and endpoint definitions are described, some serious-event counts are listed, and the primary numerical result and its uncertainty are unavailable. No conclusion about treatment benefit or lack of benefit follows from the information reported.

13. Why This Trial Matters Statistically

This trial is statistically notable because it connects a pediatric transplant setting with a pharmacokinetic endpoint measured over time. AUC compresses a concentration-time profile into a single exposure measure, while the scheduled plasma sampling and compartmental modeling provide the stated basis for estimating that profile. The endpoint is distinct from clinical-event outcomes such as cytomegalovirus disease or graft loss.

The age-based regimen categories also highlight an important design distinction. Different age categories can be used to describe dosing and safety, but they are not equivalent to randomized treatment groups. Statistical comparisons between them would be observational and could be affected by characteristics that differ across age groups. The registry describes no randomized comparator.

The record illustrates why endpoint definitions alone are not enough for interpretation. It identifies the measure, units, dispersion statistic, sampling schedule and analysis population, but does not report the numerical AUC result or its uncertainty. Without those quantities, the reader cannot judge the magnitude, spread or precision of the primary estimate.

Finally, the primary population spans three named studies, while the registry also reports enrollment for the study record. The description of the analysis population and the note about one participant not being analyzed are essential context, but further information on the relationship between populations and missing measurements is not reported in the registry record. Together, these features make the study a useful example of how design, analysis population and reporting completeness determine what can be inferred.

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 most consequential limitation for interpretation is that the registry record does not report numerical results for the primary endpoint. The mean AUC and standard deviation are named, but their values are not reported. A confidence interval and inferential analysis are also not reported, preventing assessment of precision or statistical evidence.

The design is non-randomized and single-group, with no separate comparator described. Consequently, the study record does not provide a randomized basis for attributing differences in outcomes to treatment. Its age categories are regimen groups rather than randomized arms, and the record does not report adjusted comparisons between them.

The primary pharmacokinetic population is described as participants from studies WP16296, WP16303 and WV16726 who completed specified treatment and provided at least one plasma sample. The relationship between that population and the study enrollment of 63 is not fully explained. The record notes one participant excluded from the primary endpoint analysis after both a kidney and liver transplant, but does not describe the broader pattern of missing data or how missing measurements were handled.

The record states that a compartmental model was used but does not report its structure, estimation details or diagnostics. It does not report a detailed statistical analysis plan, multiplicity strategy, sample-size justification or the numerical results for the listed secondary outcomes. Serious adverse-event percentages are posted, but the denominator details and event attribution are not reported in the registry record. These omissions limit assessment of the primary estimate, the secondary outcomes and safety comparisons.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Valcyte (Valganciclovir) Syrup Formulation in Pediatric Solid Organ Transplant Recipients — NCT00090766.
• Registry record last updated 2016-10-31; status last verified 2016-03.
• Results first posted 2016-10-31.
• 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

This completed, non-randomized, single-group study assessed the safety and pharmacokinetics of oral valganciclovir in pediatric solid organ transplant recipients. The registry lists Phase 2 and Phase 3, enrollment of 63, and age-based regimen groups. Treatment was described as oral solution or tablets, beginning at kidney transplantation and continuing for up to 100 days after transplant, with a maximum daily dose of 900 mg.

The primary endpoint was mean AUC from 0 to 24 hours, measured using a compartmental model and summarized with standard deviation. The pharmacokinetic population is described across studies WP16296, WP16303 and WV16726. Numerical primary and secondary outcome results are not reported in the registry record. Serious adverse-event counts by age group and several serious-event percentages are listed, but no comparative or causal interpretation is supported by the design description.