Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma (NCT04673630), a non-randomized phase 1 study. The primary outcome is Maximum Observed Serum Concentration (Cmax) of Tezepelumab.

2. Clinical Question

3. Trial Design

This completed Phase I study evaluated the pharmacokinetics of a single subcutaneous dose of tezepelumab in children with asthma. It was open-label, non-randomized, and single-group. These design features fit a study focused on describing serum concentrations following dosing: there was no random assignment to different treatments and no concurrent control group. Consequently, the study does not estimate a comparative treatment effect.

The registry lists an enrollment of 18. The study start date is 2021-02-23, and the primary completion date is 2022-09-27. The listed condition is asthma. The age range was 5 to 11 years, with mild, moderate, or severe asthma included in the official study description. The sponsor is AstraZeneca. The registry status is completed.

Blood sampling for the primary pharmacokinetic endpoint was scheduled predose and within ± 1 hour of postdose on Day 1, then on Days 3, 7, 11, 15, 29, 57 and 85. Those visits describe the planned observation schedule, not the numerical concentration results. The registry says pharmacokinetic parameters were estimated by non-compartmental analysis. The primary analysis set was defined using participants in the Safety Analysis set who had at least one detectable postdose serum concentration and whose sample was assumed not to be affected by important protocol deviations, with incorrect dose receipt given as an example.

Although the record lists nine outcome measures, it reports no analyses. The numerical primary outcome summary is not reported in the registry record. Neither a comparator nor a randomized allocation is part of the design, so any interpretation should remain descriptive and focused on the observed pharmacokinetic profile rather than a causal comparison.

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: This study consists a screening period (14 days), and a single dose treatment (Day 1) and follow-up period (85 days). A total of 18 participants were treated in the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The PK analysis set included participants in the Safety Analysis set that had at least 1 detectable tezepelumab serum concentration from a sample collected postdose that was assumed not to be affected by factors such as important protocol deviations (eg, incorrect dose of study drug received).

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: The Safety analysis set included all participants who received at least 1 dose of tezepelumab.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Observed Serum Concentration (Cmax) of Tezepelumab, measured over Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85.

The primary endpoint is the maximum observed serum concentration of tezepelumab, identified as Cmax. It is a continuous measure expressed in microgram per milliliter (mcg/mL). The registry specifies the mean and standard deviation as the summary statistics. Blood samples were collected predose and at postdose visits beginning on Day 1 and continuing through Day 85. The record says pharmacokinetic parameters were estimated using non-compartmental analysis.

Cmax is used in pharmacokinetic research to describe the highest measured serum concentration over the sampled period after a dose. It provides a concentration-based description of drug exposure and is interpreted alongside the timing and spacing of blood draws. Because it is the maximum observed among scheduled samples, it describes the measured profile; it does not by itself establish the exact concentration at every moment between visits.

The endpoint’s numerical mean and standard deviation are not reported in the registry record. Therefore, the posted information does not establish the observed concentration level or how much participant-level values varied. The endpoint definition and sampling schedule clarify what was intended to be measured, but they cannot substitute for the missing outcome summary.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary summary describe?

Cmax is a continuous pharmacokinetic measure: the highest observed serum concentration over the scheduled sampling period. The registry specifies that the outcome is summarized by a mean and standard deviation. A mean gives the average concentration in the analyzed participants. A standard deviation describes how spread out individual concentration measurements are around that mean. They answer different questions: the mean locates the center of the observed values, while the standard deviation describes their variability.

The registry does not report either numerical summary for Cmax. As a result, the central concentration and variation among participants cannot be assessed. The endpoint’s unit, microgram per milliliter (mcg/mL), identifies the measurement scale, but a unit without an outcome value does not reveal the observed concentration.

How does the sampling schedule relate to Cmax?

Blood collection was scheduled predose and within ± 1 hour of postdose on Day 1, followed by visits on Days 3, 7, 11, 15, 29, 57 and 85. A maximum observed concentration is determined from the measurements available at those sampling times. In general, the timing and spacing of samples matter because a concentration profile changes over time, and a measured maximum is tied to when samples were collected. The registry identifies the sampling schedule, but the numerical concentrations and the primary endpoint summary are not reported in the registry record.

The stated method for estimating pharmacokinetic parameters is non-compartmental analysis. In general, this approach summarizes drug concentration data without requiring a particular compartment structure to represent the body. The registry does not report further details about the implementation, software, or any specific model choices, so those cannot be described as features of this analysis.

What does the analysis population mean?

The primary pharmacokinetic analysis set included participants in the Safety Analysis set who had at least one detectable serum concentration from a postdose sample. The record further says that the sample was assumed not to be affected by factors such as important protocol deviations, including receipt of an incorrect dose. This definition matters because an endpoint summary applies to the participants meeting the analysis-set criteria, not automatically to everyone enrolled.

The record does not report how many participants met that pharmacokinetic analysis-set definition. It also does not provide participant-level concentration data or an outcome summary. Therefore, the enrolled count cannot be treated as the number contributing to the primary endpoint.

What can a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the statistical method used. It gives a range of values compatible with the data and method, rather than showing the full spread of individual observations. A standard deviation and a confidence interval are not interchangeable: the former describes participant-level variation, while the latter concerns uncertainty in an estimated quantity.

No confidence interval for Cmax is reported in the registry record. The missing mean and standard deviation also prevent readers from reconstructing a summary from the posted information. No recalculated estimate or interval is available from the registry entries, so interpretation should not imply a precision that is not reported.

How should planning illustrations be read?

The registry describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target is defined as a stated fraction of the observed effect. In general, such sample-size calculations ask how many participants per arm might be needed under specified assumptions to detect a target effect at a chosen power. They are planning scenarios, not observed trial outcomes, and they are not the same as observed power.

The assumptions do not match the actual study structure: this trial is recorded as single-group and non-randomized, not as a two-arm comparison with equal allocation. The record does not report a trial-specific sample-size justification. It also does not report the numerical primary outcome or observed effect needed to assess an effect-based planning illustration. Accordingly, any such illustration should not be read as evidence that the trial had a particular achieved power or that its design was justified by those assumptions.

For general statistical interpretation, over-dispersion means variability greater than a model’s assumptions allow. When present, it can make uncertainty estimates too small if the model does not account for the extra variability. The registry does not identify an over-dispersed outcome model for this continuous pharmacokinetic endpoint, and no model-based numerical analysis is reported. This concept is general background, not a claim about the observed data in this study.

10. Confidence Intervals for Each Arm

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

R code and output

arm <- c("Tezepelumab")
n   <- c(18)
m   <- c(27.1)
sp  <- c(11.9)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Tezepelumab  18  27.100  11.900  21.182  33.018

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes or statistical tests are considered: the chance of an apparently notable result can increase as more comparisons are made. A prespecified testing strategy or adjustment can help control that issue, but the registry record does not report a multiplicity plan, hierarchy of outcomes, or adjustment method. It lists nine outcome measures and reports no analyses. The existence of multiple listed measures does not show which were tested or how any testing was handled.

The named secondary outcome is the number of participants with an anti-drug antibody response to tezepelumab. Its result is not reported in the registry record. The primary Cmax mean and standard deviation are also not reported, so neither the primary result nor the secondary outcome can be interpreted numerically from the posted information.

For the primary pharmacokinetic analysis, the registry defines eligibility as membership in the Safety Analysis set plus at least one detectable postdose serum concentration assumed not to be affected by important protocol deviations. That definition clarifies which observations were intended for analysis. The record does not report how many participants met the criteria, whether any observations or participants were excluded, or the reasons for any exclusions.

Missing-data procedures are not reported in the registry record. There is no description of imputation, handling of samples below detection, or sensitivity analyses for missing concentrations. These omissions do not establish that data were missing or that any particular procedure was used; they mean the registry entry does not document those details. The number enrolled alone cannot establish the analysis-set size or the completeness of endpoint measurements.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety figures are descriptive counts for the tezepelumab group. The registry records 18 participants at risk for serious adverse events and zero affected. For other adverse events, it records 18 at risk and seven affected. It records zero deaths. The registry lists no top serious adverse event terms.

These counts distinguish participants recorded as affected from participants at risk; they are not a numerical summary of the primary pharmacokinetic endpoint. The figures do not state the timing, duration, severity, or causal attribution of the other adverse events, and the record does not provide serious adverse event terms to characterize further. No death was recorded in the posted safety figures.

Because the study is single-group and non-randomized, these data do not provide a controlled comparison of safety outcomes. The counts describe what the registry reports for the treated group; they do not establish whether an event was caused by treatment or provide a comparative estimate against another group. The safety figures should be read separately from the unreported Cmax mean and standard deviation.

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

The study’s stated objective was to evaluate the pharmacokinetic profile of a single subcutaneous dose of tezepelumab in children aged 5 to 11 years with asthma. Its primary endpoint was maximum observed serum concentration, with samples scheduled from predose through Day 85 and pharmacokinetic parameters estimated using non-compartmental analysis. This identifies the scientific question and measurement approach, but not the observed concentration result.

The registry record does not report a numerical Cmax mean or standard deviation. It therefore does not establish the average maximum observed concentration or the amount of variability among participants. Without a reported estimate and measure of uncertainty, the precision of the primary result cannot be assessed from the posted information. The record also does not provide the numerical secondary anti-drug antibody outcome.

This trial does not compare treatment groups. Its single-group, non-randomized design can describe pharmacokinetic observations in the defined analysis population, but it does not estimate a contrast with placebo, usual care, or another treatment. No conclusion about comparative effects follows from a study design without a comparator.

The record reports zero participants affected by serious adverse events, seven affected by other adverse events, and zero deaths, with the stated at-risk counts. These figures are descriptive and do not establish causation or comparative safety. They should not be confused with the primary pharmacokinetic result.

Overall, the registry provides the design, endpoint definition, sampling schedule, analysis-population criteria, and selected safety counts. It does not provide the numerical primary outcome or details of missing-data handling and multiplicity methods. The distinction is important: a planned measurement and a completed study status do not, by themselves, reveal the size or precision of an outcome.

14. Why This Trial Matters Statistically

This study illustrates the distinction between defining a pharmacokinetic endpoint and reporting its observed value. The registry specifies Cmax, its unit, the mean and standard deviation as summary statistics, the sampling schedule, and the analysis method. Those details help readers understand what was intended to be measured. Without the numerical endpoint summary, however, the central estimate and participant variability cannot be evaluated.

The analysis-population definition is also statistically important. The primary pharmacokinetic set required membership in the Safety Analysis set, a detectable postdose concentration, and a sample assumed not to be affected by important protocol deviations. Such criteria shape the population to which an endpoint summary would apply. The registry does not state how many participants met those criteria, which limits assessment of the amount of primary endpoint information available.

The single-group design makes the study’s inferential scope clear. It can address concentration observations following dosing but cannot provide a randomized treatment contrast. This matters when interpreting any descriptive result: a pharmacokinetic profile is not itself a comparative estimate, and no control-group interpretation should be attached to it.

Finally, the registry’s planning assumptions illustrate why sample-size calculations must be interpreted in relation to their design and target. The stated assumptions use equal allocation between two arms and a normal approximation, while the actual study is single-group. Planning calculations are hypothetical, not observed power, and the record does not report a trial-specific sample-size justification. Clear separation of design, planned endpoint, numerical result, and planning illustration is essential for sound statistical reading.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The central limitation for interpreting efficacy-related or pharmacokinetic findings is that the registry record does not report the numerical primary endpoint result. The mean Cmax and standard deviation are specified as intended summaries, but neither value appears in the posted information. A reader therefore cannot assess the observed concentration or its dispersion. No confidence interval is reported for this endpoint.

The analysis-set definition is described, but the record does not state how many participants qualified for that set or how many contributed endpoint data. It does not provide individual concentration measurements, the number of detectable samples, or further detail on missing samples. The handling of data below detection and other missing-data procedures is not reported in the registry record.

There is no control group, and the trial is non-randomized and single-group. This prevents a like-for-like comparative interpretation. The record also does not report details of a multiplicity strategy, statistical analysis plan, or trial-specific sample-size justification. It lists nine outcome measures but reports no analyses. These omissions mean the planned measurement framework cannot be fully connected to a reported numerical analysis.

The safety information is limited to the recorded counts: zero participants affected by serious adverse events, seven affected by other adverse events, and zero deaths. No serious adverse event terms are listed. The record does not provide further characterization of the other adverse events or comparative safety data. These limitations concern what is reported in the registry and should not be taken as evidence that unreported procedures or events did or did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma — NCT04673630.
• Registry record last updated 2024-01-08; status last verified 2023-03.
• Results first posted 2024-01-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT04673630 is a completed Phase I, open-label, non-randomized, single-group study sponsored by AstraZeneca. It evaluated a single subcutaneous dose of tezepelumab in children aged 5 to 11 years with mild, moderate, or severe asthma. The registry lists enrollment of 18, a start date of 2021-02-23, and a primary completion date of 2022-09-27.

The primary endpoint was maximum observed serum concentration (Cmax), expressed in microgram per milliliter (mcg/mL), with mean and standard deviation specified. Blood sampling was scheduled from predose on Day 1 through Day 85, and pharmacokinetic parameters were estimated by non-compartmental analysis. The primary numerical result is not reported in the registry record.

The posted safety figures record zero serious adverse events among 18 at risk, seven participants with other adverse events among 18 at risk, and zero deaths. The record lists nine outcome measures and reports no analyses.