Afatinib in Subjects With Kidney Dysfunction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Afatinib in Subjects With Kidney Dysfunction (NCT02096718), a non-randomized phase 1 study. The primary outcome is AUC 0-tz of Afatinib (BIBW 2992).

2. Clinical Question

3. Trial Design

This was a phase 1, mono-centric, open-label study with a matched-group design. The registry lists non-randomized allocation and a parallel model. Participants were assigned to groups according to renal-function category rather than by random allocation. The registry describes healthy participants as matched to participants with moderate or severe renal impairment by gender, race, age and BMI. It does not report how matching was performed or how many matched sets were formed.

The study investigated pharmacokinetics and safety after a single dose of afatinib. The three listed groups were healthy participants, participants with moderate renal impairment and participants with severe renal impairment. The overall enrollment was 30. The registry record does not report the dose amount or the criteria used to classify the severity of renal impairment.

The study status is completed. Its start is recorded as 2014-05 and its primary completion as 2014-12. These dates describe the registry record; they do not supply details about recruitment duration, follow-up, or the timing of individual assessments beyond the stated pharmacokinetic sampling schedule.

Because allocation was not randomized, observed group differences can reflect differences between the groups as well as any association with renal-function category. Matching addresses only the characteristics named in the registry description, and the record does not report enough detail to assess the matching process or other potential differences between groups. The registry does not report a randomized treatment comparison or a protocol-specific statistical plan.

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 was a non-randomised, non-controlled, open-label, single-dose trial with matched group design. Group 1 contained subjects with moderate renal impairment, Group 2 subjects with severe renal impairment, and Group 3 subjects with normal renal function; groups were dosed sequentially.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic set (PKS): included all patients in the treated set who provided evaluable data for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK.

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: (Treated Set) All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment. All 30 subjects were included in the treated set (TS)

6. Primary Endpoint

The registry lists the primary outcome as AUC 0-tz of Afatinib (BIBW 2992), measured over PK plasma samples were taken at: 1 hour before drug administration and 0.5 hour (h), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 312h after first drug administration.

The primary endpoint is AUC 0-tz of afatinib, reported in ng*h/mL. AUC means area under the concentration-time curve: it summarizes measured plasma concentrations across a stated time interval. For this endpoint, the interval runs from time zero to the last quantifiable data point. The registry describes the endpoint as a geometric mean, with geometric coefficient of variation as its dispersion measure.

Pharmacokinetic AUC is used to summarize overall drug exposure across the measurement interval, rather than describing concentration at only one sampling time. Comparing this measure across renal-function groups addresses the study’s stated objective of investigating the influence of renal impairment on afatinib pharmacokinetics. It does not, by itself, describe every aspect of the concentration profile or establish a clinical effect.

Plasma sampling was scheduled before dosing and at the listed post-dose times through 312h after first drug administration. The registry identifies the pharmacokinetic set as treated participants with evaluable data for at least one primary pharmacokinetic endpoint and without important protocol violations relevant to the pharmacokinetic evaluation. Numerical AUC results by group, and a numerical comparison between groups, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes AUC 0-tz as the primary pharmacokinetic endpoint and specifies a geometric mean with geometric coefficient of variation. In general, AUC reduces a series of concentration measurements to a measure of exposure over a defined interval. Here, the interval is from time zero through the last quantifiable data point. The scheduled plasma sampling times are intended to capture the concentration profile over that interval; the registry lists samples before dosing and after dosing through 312h. The listed schedule does not itself show how many samples were evaluable or how missing measurements were handled.

A geometric mean is a summary on a multiplicative scale. In general, analyses using this scale transform positive measurements to logarithms, summarize them, and transform the summary back. This can be useful when values vary proportionally rather than by a constant additive amount. A geometric coefficient of variation is a measure of relative variability associated with that scale. The registry identifies these summary measures but does not report the calculation details, the underlying group values, or the uncertainty around the estimates.

When comparing groups, estimates and confidence intervals serve different but complementary purposes. An estimate describes the observed contrast, while a confidence interval expresses the precision compatible with the data and the analysis assumptions. A p-value, when reported, addresses compatibility with a specified null hypothesis under those assumptions; it is not a measure of effect size or clinical importance. The registry record does not report an endpoint contrast, confidence interval, or p-value for AUC 0-tz, so none can be interpreted for this study from the record.

Because group allocation was non-randomized, the analysis is observational with respect to renal-function category. In general, random allocation helps balance measured and unmeasured baseline characteristics on average; matching can align selected characteristics but does not guarantee balance in every factor. The registry names gender, race, age and BMI as matching characteristics for healthy participants. It does not describe matching procedures, any adjustment model, or a plan to account for remaining differences. A statistical comparison would therefore need to be interpreted in light of the design and the assumptions used to address group differences.

The record lists six analyses and three outcome measures, but it does not describe the full set of analysis methods or how those analyses relate to each outcome. It does not report whether the primary endpoint was analyzed using a particular model, whether any covariates were included, how repeated measurements contributed to the endpoint, or how any protocol deviations affected analysis. These details are not reported in the registry record and should not be inferred from the endpoint’s summary measure.

The study identifies a pharmacokinetic set: treated participants with evaluable data for at least one primary pharmacokinetic endpoint and without important protocol violations relevant to the pharmacokinetic evaluation. This definition indicates that the primary analysis was not necessarily based on every enrolled participant. The record does not report the number included in this set, the number excluded, the reasons for exclusion, or whether other analysis populations were used.

Sample-size calculations are planning illustrations rather than observed trial findings. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a stated fraction of the observed effect. For time-to-event calculations, the stated convention is total events; for other calculations, it is participants per arm. These assumptions do not establish that the study itself used that design or analysis. The registry does not report its own sample-size justification, and numerical planning outputs are not reported in the registry record.

In general, over-dispersion means that variability is greater than a model assumes. If present, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for it. This is a general statistical consideration; the registry does not report an over-dispersion assessment or indicate that it was relevant to this endpoint.

Safety outcomes are described as evaluated with descriptive statistics. Descriptive counts convey what was recorded in the observed groups, while inferential methods would be needed for a formal estimate of comparative uncertainty. The registry record does not report a formal safety comparison or details such as event definitions and the handling of repeated events. As a result, the posted counts can be read as recorded event summaries but not as evidence of a precise between-group difference.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint, AUC 0-tz of afatinib, and identifies AUC 0-inf as a secondary outcome. It also lists three outcome measures and six analyses. The record does not explain how the analyses map to the outcomes, which comparisons were prespecified, or whether any outcomes or analyses were exploratory.

Multiplicity arises when several outcomes, comparisons or analyses are considered. In general, making many statistical tests can increase the chance of at least one apparently unusual result if no adjustment or interpretive plan is specified. A multiplicity strategy might define a hierarchy, adjust significance thresholds, or treat secondary analyses as descriptive. The registry does not report a multiplicity adjustment, testing hierarchy or other multiplicity plan, so it is not possible to determine how multiple analyses were handled.

The record defines the pharmacokinetic set as treated participants with evaluable data for at least one primary pharmacokinetic endpoint and without important protocol violations relevant to the pharmacokinetic evaluation. Its size, exclusions and missing-data handling are not reported in the registry record. The record also does not report whether participants with incomplete sampling contributed to any endpoint, how a last quantifiable data point was determined in practice, or whether any imputation was used.

The registry’s safety figures include denominators for each group, but a full participant disposition by analysis population is not reported. These omissions limit assessment of whether the populations contributing to the endpoint analyses differed across groups or whether missing information could affect interpretation. The registry also does not report interim analyses, a detailed statistical analysis plan, or a sample-size justification.

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 non-serious adverse event terms

The posted serious adverse-event figures list 14 participants at risk in the healthy group, 8 in the moderate renal impairment group and 8 in the severe renal impairment group. The corresponding numbers affected by serious adverse events are 0, 0 and 0. Deaths are not reported in the registry record.

For adverse events other than serious events, the figures list 4 affected participants among 14 in the healthy group, 2 among 8 in the moderate impairment group and 0 among 8 in the severe impairment group. These are descriptive counts within the recorded groups. The registry does not provide further definitions or detail about the events, such as their types or severity, and does not report a formal comparative analysis.

Small group counts can leave substantial uncertainty about how well observed event patterns represent a broader population. A count of zero serious events in a group does not establish that the underlying risk is zero. The safety figures should therefore be read as the events recorded in these study groups, not as proof that groups differ or do not differ in safety.

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

The record shows that a phase 1 study was conducted to investigate afatinib pharmacokinetics after a single dose in participants with moderate or severe renal impairment, in comparison with participants with normal renal function. It specifies AUC 0-tz as the primary endpoint and describes the intended safety assessment. It also reports the study’s non-randomized, open-label, matched-group design and the scheduled pharmacokinetic sampling.

The record does not report numerical AUC 0-tz results, group estimates, a between-group contrast, confidence intervals or p-values. It is therefore not possible to say from the registry record whether exposure was higher or lower in either renal impairment group, or how precisely any difference was estimated. The endpoint definition describes what was intended to be measured, not the result of that measurement.

The non-randomized design matters because differences between the groups cannot be attributed to renal-function category alone without considering other group characteristics and analysis assumptions. Matching by gender, race, age and BMI is described, but the record does not report matching details or enough information to evaluate residual differences. The findings, even if numerical results were available, would need interpretation in the context of this design.

The adverse-event counts describe recorded events in the listed safety groups. They do not establish a comparative safety effect, and the absence of recorded serious events does not establish an absence of risk. The registry also does not report deaths, event details or a formal safety analysis.

Planning illustrations, if considered, concern hypothetical design assumptions and are not observed power. They cannot replace the missing endpoint estimates or uncertainty measures. In short, the record identifies the clinical and statistical question and offers limited descriptive safety counts, but does not report the numerical primary result needed to characterize pharmacokinetic differences.

13. Why This Trial Matters Statistically

This study is statistically notable for asking a pharmacokinetic question across renal-function groups using a matched, non-randomized design. The endpoint, AUC 0-tz, summarizes plasma exposure over a defined interval and is paired with a geometric mean and geometric coefficient of variation. That choice makes the scale of the summary explicit, while also highlighting the importance of reporting group estimates and their uncertainty for interpretation.

The matching description names gender, race, age and BMI. Those features clarify which characteristics the registry intended to align, but matching alone does not make groups equivalent in all respects. The non-randomized allocation means that interpretation depends on how the groups compare and on the analysis used to account for differences. The registry record does not give enough detail to assess those elements.

The record also illustrates why endpoint definitions and results must be distinguished. A clear endpoint definition and detailed sampling schedule explain what investigators intended to measure. Without numerical estimates and uncertainty measures, however, those design details cannot establish the magnitude, direction or precision of an observed difference.

Finally, the safety summaries are descriptive and based on the listed group denominators. They are useful for identifying what the registry records, but the modest group counts and lack of event detail limit broader interpretation. The absence of reported primary pharmacokinetic results is especially important: the study’s central statistical question remains unanswered by the numerical results in the 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 most important limitation for interpreting results is that the registry record does not report numerical results for the primary endpoint. It gives no group-specific AUC 0-tz estimates, contrast, confidence interval or p-value. The direction and precision of a pharmacokinetic difference therefore cannot be assessed from this record.

The study was non-randomized. Although the healthy group is described as matched by gender, race, age and BMI to participants with renal impairment, the matching procedure and achieved balance are not reported. The record does not describe adjustment for other characteristics or explain how any remaining group differences were handled.

The record does not report the dose amount, criteria defining moderate and severe renal impairment, or the size and disposition of the pharmacokinetic set. It defines that set by treatment, evaluable primary endpoint data and absence of important relevant protocol violations, but does not say how many participants met those criteria or how exclusions and incomplete data were handled.

The safety information is limited to counts of participants affected. Deaths are not reported in the registry record, and further event descriptions, definitions and formal comparative safety analyses are also not reported. In addition, the registry does not report the statistical analysis plan, sample-size justification, multiplicity approach or interim analyses. These omissions constrain assessment of the methods and the strength of conclusions that could be drawn from the posted record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Afatinib in Subjects With Kidney Dysfunction — NCT02096718.
• Registry record last updated 2016-01-14; status last verified 2015-11.
• Results first posted 2016-01-14.
• 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

NCT02096718 is a completed phase 1, mono-centric, open-label, non-randomized study of single-dose afatinib in healthy participants and participants with moderate or severe renal impairment. Enrollment was 30. The healthy participants were described as matched to impaired participants by gender, race, age and BMI.

The primary endpoint was AUC 0-tz of afatinib, summarized as a geometric mean with geometric coefficient of variation. AUC 0-inf was listed as a secondary outcome. Safety and tolerability were additional objectives and were to be evaluated descriptively.

The registry reports group denominators and adverse-event counts, but does not report numerical results for the primary pharmacokinetic endpoint. Detailed analysis methods, missing-data handling, multiplicity procedures and the study’s sample-size justification are not reported in the registry record.