Gadopiclenol Pharmacokinetics, Safety and Efficacy in Children < 2 Years of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gadopiclenol Pharmacokinetics, Safety and Efficacy in Children < 2 Years of Age (NCT05590884), a non-randomized phase 2 study. The primary outcome is Area Under the Curve (AUCinf).

2. Clinical Question

3. Trial Design

This was a Phase II, open-label, uncontrolled, multicenter trial of gadopiclenol in pediatric patients up to 23 months of age. The registry record lists an enrollment of 36 and a completed status. The study started on 2022-09-21, with primary completion on 2024-09-30. The sponsor was Guerbet.

Patients were divided into age groups: 3 to 23 months, 28 days to less than 3 months, and birth to 27 days for term newborns. Each group received one intravenous injection of gadopiclenol at 0.05 mmol/kg body weight. Participants were scheduled for contrast-enhanced MRI of any body region, including the central nervous system. There was no placebo or active comparator, and allocation was non-randomized. The age groups therefore provide a framework for describing pharmacokinetics across ages, not a controlled estimate of a treatment effect.

The primary objective was to investigate plasma pharmacokinetics using a population PK approach. The endpoint description identifies AUCinf as an exposure parameter predicted by the final model for each age group among participants with normal renal function. The registry reports three post-injection blood-sampling windows: 10-60 minutes, 2-4 hours, and 6-8 hours. These sparse measurements were intended for analysis with the population model, rather than to describe every participant’s complete concentration-time profile directly.

The registry record states that 36 patients received an injection for MRI in the Safety Set. It also states that 35 patients were included in the population PK analysis, after the patient aged 0-27 days was excluded from the Per Protocol Set because of a major deviation affecting the population PK model. The study’s detailed protocol, rationale for its enrollment target, and statistical analysis plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Among the 36 patients who received an injection of gadopiclenol for MRI (Safety Set), the patient aged 0-27 days was excluded from the Per Protocol Set, due to a major deviation impacting the popPK model, therefore 35 patients were included in the population PK analysis including 33 patients aged 3-23 months and 2 patients aged 28-89 days.

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: Baseline analysis population included 36 patients who received one injection of gadopiclenol (safety set): 33 patients aged 3 to 23 months, 2 aged 28 days to less than 3 months and 1 patient aged 0-27 days.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Curve (AUCinf), measured over A total of 3 blood samples per patient were collected post-injection of gadopiclenol for PK analysis, one within each window (10-60 minutes, 2-4 hours and 6-8 hours).

The primary endpoint was AUCinf, reported as a geometric mean with geometric coefficient of variation. AUCinf represents the area under the plasma concentration-time curve extrapolated to infinity. In general, area under a concentration-time curve is used as a measure of overall drug exposure; extrapolation extends the measured profile beyond the observed sampling period using a model. The endpoint is therefore relevant to a pharmacokinetic objective, rather than a direct measure of MRI image quality or clinical benefit.

The registry describes the endpoint as an exposure parameter by age group predicted from the final population PK model. The stated population was participants with normal renal function who received gadopiclenol at 0.05 mmol/kg. Three post-injection blood samples per patient were collected, one in each of the 10-60 minutes, 2-4 hours, and 6-8 hours windows. A population model can use the combined concentration data to estimate a shared pharmacokinetic pattern while accounting for differences among participants. This approach is useful when only a limited number of samples are collected from each participant.

A geometric mean summarizes measurements on a multiplicative scale and is commonly used for exposure measures with a skewed distribution. The geometric coefficient of variation describes relative variability on that scale. These summaries do not, by themselves, show how precise the estimate is: an interval estimate or other uncertainty measure is needed to assess that. Numerical AUCinf results and their geometric coefficients of variation are not reported in the registry record, so the magnitude and precision of the estimated exposure cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary objective was pharmacokinetic: to characterize plasma exposure after a single intravenous injection. The registry describes a population pharmacokinetic approach, with AUCinf predicted by the final model for each age group. General explanation: pharmacokinetics concerns how drug concentrations change over time in the body. A population approach estimates shared features of those concentration patterns while allowing for variation between participants. It can be useful when each participant contributes only a small number of blood samples.

Why use a population model?

General explanation: a concentration-time profile is usually built from measurements taken at different times after dosing. When blood collection is limited, the observations from a group can be analyzed together rather than treating each participant’s few measurements as a complete profile. A model can use the sampling times, measured concentrations, and participant characteristics to estimate population-level parameters. The usefulness of this approach depends on the model’s assumptions, the quality and timing of measurements, and the amount of information available. The registry identifies a final model but does not report its structure, covariates, diagnostics, or parameter uncertainty. Those details are not reported in the registry record.

In this study, three blood samples per patient were planned after injection, with one sample in each of the 10-60 minutes, 2-4 hours, and 6-8 hours windows. The primary endpoint was not simply a concentration at one collection time. It was AUCinf, an area-under-the-curve measure predicted from the model. General explanation: the area under a concentration-time curve combines information across time and is used to represent overall exposure. The “inf” indicates that the area is extrapolated to infinity, so the estimate depends partly on the model’s representation of the concentration profile beyond the measured sampling period.

What do the endpoint summaries mean?

The endpoint was summarized as a geometric mean, with geometric coefficient of variation. General explanation: a geometric mean is calculated on a multiplicative scale and is often useful when positive measurements are skewed or vary proportionally. It is not the same summary as an arithmetic average. The geometric coefficient of variation describes the degree of relative variability around a geometric-scale summary. It does not replace a confidence interval, and it does not alone show the precision of the estimate. Numerical values for the primary endpoint are not reported in the registry record, so neither the exposure estimates nor their dispersion can be interpreted from the posted record.

The endpoint description specifies that estimates were predicted by age group among participants with normal renal function who received 0.05 mmol/kg. That target population is narrower than a general statement about all children up to 23 months: it is defined by the renal-function condition and the study’s treatment and sampling context. The registry record does not describe how normal renal function was defined, or whether the final estimates were adjusted for other characteristics.

Why do the age groups not form a randomized comparison?

The trial was non-randomized, open-label, and uncontrolled. General explanation: randomization is used in comparative trials to make assigned groups comparable, on average, with respect to measured and unmeasured characteristics. It does not apply because the age categories are not randomized treatment assignments. All participants received the same stated dose, and there was no control group. Differences between age-group estimates, if available, would be descriptive. They could reflect age as well as other differences in the participants or the data contributing to the model.

The sample-size assumptions recorded for planning illustrations specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects expressed as a stated fraction of an observed effect. Those assumptions describe planning calculations, not the design or analysis of this uncontrolled trial. The record does not report a trial-specific sample-size justification, and the planning illustrations should not be read as observed power or as evidence that a treatment effect was demonstrated.

What can event counts tell the reader?

The registry reports counts of participants affected by serious adverse events and other adverse events, organized by age group, as well as deaths and listed serious-event terms. General explanation: a count conveys how many participants in a defined group had at least one recorded event of the stated type. It is not a causal estimate. Without a control group, an event count cannot distinguish events attributable to the study drug from events that would occur for other reasons. The registry record does not report confidence intervals or comparative tests for these safety outcomes. The small age-group counts also make the figures particularly limited for evaluating uncommon events.

10. Multiplicity, Missing Data and Analysis Populations

The registry record describes one primary objective: evaluation of plasma pharmacokinetics after a single injection. AUCinf is identified as the primary endpoint, with estimates predicted by age group from the final population PK model. The record does not report a multiplicity strategy, such as how statistical error would be controlled across multiple endpoints, age-group estimates, or safety outcomes. It also does not report a detailed statistical analysis plan or identify any confirmatory hypothesis tests.

The record lists 10 outcome measures, but that count does not explain how outcomes were prioritized or how multiple analyses were handled. No analyses are listed in the registry record. Numerical results for the primary endpoint are not reported there, and the described endpoint summary alone does not supply confidence intervals or other measures of precision.

The registry states that 36 patients who received an injection for MRI were in the Safety Set. It states that 35 patients were included in the population PK analysis, after the patient aged 0-27 days was excluded from the Per Protocol Set because of a major deviation affecting the population PK model. The record further identifies 33 patients aged 3 to 23 months in that analysis. These analysis populations differ by purpose: the Safety Set is used for safety reporting, while the population PK analysis concerns model-based exposure estimation. The record does not fully describe the membership or handling of the remaining age-group observations in the pharmacokinetic analysis.

The sampling description calls for three post-injection samples per patient, one in each specified window. The registry does not report whether all planned samples were collected, how missing or unusable concentrations were handled, or whether any imputation was used. It also does not report sensitivity analyses addressing the exclusion or incomplete observations. These details are not reported in the registry record, so the consequences of missing data for the endpoint estimates cannot be assessed.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: feeding disorder (3.0%), tumour excision (3.0%), pyrexia (3.0%), microcytic anaemia (3.0%), gastroenteritis norovirus (3.0%).

The safety figures are counts of participants affected within each age group, not a comparison with an untreated or alternative-treatment group. Among patients aged 3 to 23 months, 8 of 33 were affected by serious adverse events and 13 of 33 were affected by other adverse events. Among patients aged 28 days to less than 3 months, the counts were 0 of 2 for serious adverse events and 2 of 2 for other adverse events. Among term newborns from birth to 27 days, the counts were 0 of 1 for serious adverse events and 0 of 1 for other adverse events. The registry reports no deaths in any group.

The listed serious-event terms include Feeding Disorder, Tumour Excision, Pyrexia, Microcytic Anaemia, Gastroenteritis Norovirus, and Pneumonia Parainfluenzae Viral, each reported at 3.0%. These entries describe recorded events; they do not establish that gadopiclenol caused them. The registry record does not report a control group, comparative safety analysis, or uncertainty intervals for these counts. The counts in the younger age groups are especially limited in what they can establish about event frequency. Read them as descriptive observations in this study, not as estimates of a causal treatment effect or as a basis for comparing risks across ages.

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

The study addresses how gadopiclenol exposure was to be characterized in pediatric patients up to 23 months of age undergoing contrast-enhanced MRI. Its primary endpoint was model-predicted AUCinf by age group, among participants with normal renal function who received 0.05 mmol/kg. The record describes the population PK approach and the post-injection sampling windows, but does not report numerical AUCinf estimates or their uncertainty. As a result, the posted record does not show the estimated exposure level, how variable the estimates were, or how precisely exposure was characterized in each age group.

The study also reports safety counts, including serious adverse events, other adverse events, and deaths. Those counts describe what was recorded among participants in the study. Because the trial was open-label and uncontrolled, the counts cannot establish whether events were caused by gadopiclenol or how safety compares with another treatment or no treatment. The absence of reported deaths in the groups is a description of this study record, not a guarantee about risk.

The findings also do not answer questions about MRI diagnostic performance, image quality, clinical outcomes, or comparative effectiveness: those are not the primary endpoint described in the registry record. The dose was the same in all age groups, and age groups were not randomized. Any contrast among age-group observations would therefore be descriptive rather than a randomized comparison. Moreover, the youngest group had very few participants, limiting what its event counts can establish.

In general, a pharmacokinetic estimate can inform understanding of drug exposure, but exposure alone is not a clinical outcome. The registry record does not report a link between the modeled AUCinf values and clinical benefit or harm. It also does not report the final model details needed to judge its fit, assumptions, or uncertainty. The record supports a description of the study question, design, analysis populations, sampling schedule, and posted safety counts; it does not support conclusions beyond those reported observations.

13. Why This Trial Matters Statistically

This trial is statistically notable for the way it frames an early-life pharmacokinetic question. It studies patients spanning term newborns through children aged 23 months and uses a population PK approach to estimate exposure from limited sampling. General explanation: population modeling can make use of measurements collected at different times from multiple participants, which is relevant when collecting many samples from each young participant is not feasible. The reliability of the resulting estimates still depends on the amount and quality of data and on the model assumptions.

The age-group structure gives the analysis a descriptive framework, but it does not create a controlled comparison. All participants received the same stated dose, and the study was non-randomized and uncontrolled. This distinction matters because differences across age groups would not have the protection against confounding that random assignment can offer. The registry record identifies the intended age-group estimates but does not report the numerical AUCinf results needed to evaluate them.

The record also illustrates why an analysis population needs to be distinguished from the safety population. It reports 36 patients in the Safety Set and 35 in the population PK analysis, with an exclusion due to a major deviation affecting the model. That distinction is relevant to interpretation: safety summaries and model-based exposure estimates draw on differently defined analysis sets. The record does not give enough detail to determine the impact of the exclusion on the estimates.

Finally, the safety counts are most informative as descriptive observations, not as comparative or causal evidence. Small group counts and the absence of a control group limit inference, while missing numerical primary endpoint results prevent assessment of exposure magnitude and precision. These features make clear the difference between a study’s stated statistical objective and the evidence available in its registry record.

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 primary limitation for interpretation is that numerical results for the primary endpoint are not reported in the registry record. Although AUCinf, its scale, dispersion measure, modeled population, and sampling windows are described, the record does not give the age-specific exposure estimates or uncertainty intervals. The final population PK model’s structure, diagnostics, parameter estimates, and sensitivity analyses are also not reported, preventing assessment of model fit and robustness.

The study was open-label, uncontrolled, and non-randomized. There was no comparator, so the design cannot estimate a comparative treatment effect or separate an event’s relation to the study drug from other causes. The age categories do not substitute for randomized arms. The registry record does not report statistical tests or uncertainty intervals for comparisons across those categories.

The sample was limited, with particularly small counts in the younger age groups. The Safety Set and population PK analysis also differed, and one patient aged 0-27 days was excluded from the Per Protocol Set because of a major deviation affecting the model. The record does not explain the broader impact of that exclusion or report sensitivity analyses.

The sampling schedule involved three post-injection windows. The registry does not report whether all samples were collected or how missing, mistimed, or unusable samples were handled. Definitions of normal renal function, detailed eligibility criteria, the sample-size rationale, and a complete statistical analysis plan are not reported in the registry record. These gaps limit assessment of generalizability, data completeness, and the basis for the modeled estimates.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Gadopiclenol Pharmacokinetics, Safety and Efficacy in Children < 2 Years of Age — NCT05590884.
• Registry record last updated 2025-10-28; status last verified 2025-10.
• Results first posted 2025-10-28.
• 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

NCT05590884 is a completed Phase II, open-label, uncontrolled, multicenter study sponsored by Guerbet. It investigated gadopiclenol pharmacokinetics in pediatric patients up to 23 months of age scheduled for contrast-enhanced MRI. The registry lists enrollment of 36 and a single intravenous dose of 0.05 mmol/kg body weight. Patients were grouped by age, and plasma sampling was described in three post-injection windows.

The primary endpoint was model-predicted AUCinf by age group, summarized as a geometric mean with geometric coefficient of variation. The registry reports that 35 patients were included in the population PK analysis after one patient aged 0-27 days was excluded from the Per Protocol Set for a major deviation affecting the model. Safety results are reported by age group, including serious and other adverse-event counts and no deaths. Numerical AUCinf results, their precision, model details, and the approach to missing data are not reported in the registry record.