A Study to Compare Pharmacokinetic and Safety of TRS003 to China-approved Bevacizumab and US-licensed Avastin®: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Compare Pharmacokinetic and Safety of TRS003 to China-approved Bevacizumab and US-licensed Avastin® (NCT03882424), a randomized phase 1 study. The primary outcome is AUC0-inf，Area Under the Serum Concentration Versus Time Curve，Time 0 to Infinity.

2. Clinical Question

3. Trial Design

NCT03882424 is a completed Phase 1 study sponsored by Zhejiang Teruisi Pharmaceutical Inc. The registry record describes a randomized, double-blind, single-dose, three-arm, parallel-group design. Participants were allocated to TRS003, China-approved bevacizumab, or US-licensed Avastin in a 1:1:1 ratio. The planned enrollment was approximately 114 healthy male participants, and the recorded enrollment was 114.

Each group received a single 3 mg/kg intravenous dose, with the study description specifying that the infusion would take place within 90 minutes. The study lasted 12 weeks according to the brief summary. Screening occurred within 28 days prior to dosing. Pharmacokinetic and immunogenicity samples were to be collected, and safety was to be assessed.

The primary objective was to assess pharmacokinetic similarity using AUC0-inf. Secondary outcomes listed in the registry record were Cmax, AUC0-last, detectable anti-drug antibodies, and adverse events. The record lists no analysis results for those secondary outcomes. It records the study as completed, with a start date of 2018-06-12 and primary completion date of 2018-09-30.

The posted pharmacokinetic summaries include 34 participants for TRS003 and 38 participants in each comparator group. The safety summaries list 38 participants at risk in each group. These analysis counts are not identical across the posted outcome summaries; the reason for the difference is not reported in the registry record. Details such as the randomization sequence, allocation concealment, and blinding procedures 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:

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.

6. Primary Endpoint

The registry lists the primary outcome as AUC0-inf，Area Under the Serum Concentration Versus Time Curve，Time 0 to Infinity, measured over Pre-dose, 0 hour (End of infusion, EOI), 0.5 hour, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours, 336 hours, 672 hours, 1008 hours, 1344 hours, 1680 hours, and 2016 hours post EOI.

The primary endpoint is AUC0-inf, the area under the serum concentration-versus-time curve from time zero to infinity. It is a pharmacokinetic measure of overall drug exposure over time. In general, exposure summaries can help characterize how much drug reaches the circulation and how that exposure compares across groups. This is a pharmacokinetic interpretation, not a clinical outcome.

The assessment schedule listed in the registry record includes pre-dose, end of infusion, and post-infusion sampling through 2016 hours. AUC0-inf is derived from concentration measurements over time and includes an estimate of exposure beyond the last measured time point. The registry labels the posted arm summaries as geometric least squares means, with standard deviations as the dispersion measure. It gives AUC0-inf units of hr*ng/mL.

The stated similarity approach compares geometric means as ratios and uses a 90% confidence interval. The registry record specifies that the interval must fall within 80-125% to conclude pharmacokinetic similarity. That is an equivalence-style criterion: the analysis asks whether the range of values reasonably compatible with the data stays inside prespecified bounds, rather than simply asking whether an ordinary difference test is statistically significant. The confidence intervals and the result of applying this criterion are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record states a specific primary statistical question but does not give a complete statistical analysis plan. It identifies AUC0-inf, the comparison of geometric means, a 90% confidence interval, and an acceptance range of 80-125%. Other choices about estimation and inference are not reported in the registry record. The methods discussion below explains the stated approach in general terms and distinguishes it from details absent from the record.

What does AUC0-inf measure?

AUC0-inf represents the area under a concentration-time curve from the start of observation through an extrapolated infinite time horizon. As a general pharmacokinetic concept, it summarizes total exposure rather than the concentration at a single sampling time. The study collected scheduled samples from pre-dose through 2016 hours after end of infusion, according to the registry record. How the extrapolated portion was estimated, how values below assay limits were handled, and how missing concentration samples were treated are not reported in the registry record.

Why compare geometric means?

Concentration and exposure measures are often analyzed on a logarithmic scale because such measures can have multiplicative variation and right-skewed distributions. A geometric mean is calculated on that scale and returned to the original scale. This is general statistical context; the registry record labels its group estimates as geometric least squares means but does not describe the transformation or model used to obtain them. A least-squares mean is generally an estimate from a statistical model, but the specific model and any covariates are not reported in the registry record.

For a similarity question, a ratio expresses one group’s estimated exposure relative to another group’s estimated exposure. The record describes ratios of geometric means but does not specify the complete set of pairwise contrasts or the exact reference coding. The three-arm design names three treatments and the primary objective refers to similarity among them. The precise comparison procedure for reaching an overall conclusion is not reported in the registry record.

How should the confidence interval be understood?

A confidence interval is a range of estimates compatible with the observed data under the analysis assumptions. Its width reflects statistical precision: a narrower interval indicates more precise estimation, while a wider one indicates more uncertainty. These are general explanations. The registry’s stated rule requires the 90% confidence interval for the geometric-mean ratio to remain within 80-125%. The interval itself is not reported, so its width, position, and relationship to the boundaries cannot be assessed.

This criterion differs from testing whether a ratio is exactly equal to a reference value. Similarity is evaluated against a range of acceptable values. A point estimate within the range would not be enough if its confidence interval extended outside it. Conversely, the decision described by the record depends on the interval and the prespecified limits, not solely on the displayed arm means. This general explanation does not establish the result for this trial.

What do the posted summaries show?

The record reports geometric least squares mean AUC0-inf values and standard deviations for each arm. The reported estimates are 30310000.0 for TRS003, 28450000.0 for China-approved bevacizumab, and 29050000.0 for US-licensed Avastin, all in hr*ng/mL. The associated standard deviations are 4780000.0, 5232000.0, and 4476000.0, respectively. These figures describe each arm’s reported summary and spread; they are not the ratio confidence intervals used by the stated similarity rule.

Standard deviation describes variability among observations around a group summary. It is not the same as a confidence interval for a treatment ratio, and it does not directly communicate the precision of the between-group comparison. The registry record does not report standard errors or confidence intervals for the arm summaries. No new inferential comparison can be reconstructed from the posted information without making assumptions that the registry does not document.

What analysis details are absent?

The record does not report the statistical model, transformation details, covariates, handling of outliers, missing-data procedures, or assumptions for the primary analysis. It also does not report whether an interim analysis took place, a sample-size justification, or the basis for the planned enrollment. The record lists 0 posted analyses. These omissions mean that readers cannot audit the full analysis pathway from the registry information alone.

The record includes a sample-size planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed with those assumptions. The registry record does not report the sponsor’s own sample-size justification. No additional sample-size values or assumptions should be inferred from the posted arm summaries.

In general, over-dispersion means that observed variability is greater than a model assumes. If present, it can make model-based uncertainty estimates too small unless the analysis accounts for it. The registry record does not report an over-dispersion assessment or a model that would permit such an assessment. This general concept therefore cannot be used to characterize the trial’s analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary pharmacokinetic endpoint, AUC0-inf, and four secondary outcomes: Cmax, AUC0-last, detectable anti-drug antibodies, and adverse events. It records no posted analyses. The record does not describe a multiplicity adjustment, a hierarchy of secondary hypotheses, or any other method for controlling the chance of false-positive findings across multiple analyses. Such a plan is not reported in the registry record.

Multiplicity is a general concern when several statistical hypotheses are tested: conducting many tests can increase the chance that at least one result appears notable by chance. A prespecified hierarchy or adjustment can address that issue, but the record does not identify one. Because the posted results include no inferential analyses for the listed secondary outcomes, there is no basis for judging how multiplicity was handled in practice.

The outcome summaries list 34 participants for the TRS003 AUC0-inf result and 38 participants for each comparator result. Safety summaries list 38 participants at risk in each group. The registry record does not explain the difference in the TRS003 counts or describe analysis populations, exclusions, withdrawals, or missing-data methods. It also does not report how missing pharmacokinetic samples or incomplete follow-up were handled.

These omissions matter because the choice of analysis population and the treatment of missing observations can affect estimates and their uncertainty. The registry record does not provide enough information to determine whether all randomized participants were included in each analysis, whether exclusions were prespecified, or whether missingness differed across groups. No assumptions about those issues can be inferred from the arm counts alone.

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 posted safety figures list 38 participants at risk in each group. No serious adverse events were recorded among participants in the TRS003, China-approved bevacizumab, or US-licensed Avastin groups. The registry record also lists zero deaths in each group. These are counts in the posted safety summary, not estimates of comparative risk or evidence from a statistical test.

The safety summary separately reports other adverse events in 6 participants receiving TRS003, 12 receiving China-approved bevacizumab, and 11 receiving US-licensed Avastin. These are counts, not rates calculated for comparison. No inferential analysis or confidence interval for adverse events is reported in the registry record. The record does not provide details about event severity, timing, duration, relatedness assessment, or the specific non-serious event terms. The listed serious-event count should therefore be read narrowly as the number recorded in the summary, not as proof that serious events are impossible or that groups differ in safety.

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

The registry record describes a randomized, double-blind study designed to compare pharmacokinetic exposure after a single dose of TRS003, China-approved bevacizumab, and US-licensed Avastin in healthy male participants. Its primary endpoint is AUC0-inf, and the stated similarity criterion is based on a 90% confidence interval for the ratio of geometric means falling within 80-125%.

The posted AUC0-inf summaries give group estimates, standard deviations, and participant counts. They allow a descriptive view of the reported exposure summaries, but they do not provide the ratio estimates or confidence intervals required by the stated decision rule. The record therefore does not establish whether pharmacokinetic similarity was concluded. Nor does the absence of a posted conclusion establish that the criterion was not met.

The study is about pharmacokinetics and safety in healthy male participants after a single dose. Its record does not establish clinical effectiveness or outcomes in people with a disease. It also does not establish how the products compare under other dosing regimens or in other populations. Those questions are outside the primary objective described in the record.

The safety summary records no serious adverse events and no deaths in the three groups, alongside counts of participants with other adverse events. Those data are descriptive. The registry record does not post formal safety comparisons or detailed event information that would support a broader interpretation. In general, a zero count in a study summary should be interpreted in the context of the study population, follow-up, and data collection; those figures do not prove that an event cannot occur.

Overall, the posted record documents the trial design and arm-level AUC0-inf summaries, but the central inferential information needed to judge the stated similarity objective is not reported in the registry record. Interpretation should remain limited to those descriptive details and to the study question and criterion as registered.

13. Why This Trial Matters Statistically

This trial raises a focused statistical question: whether pharmacokinetic exposure after a single dose is sufficiently similar across three named products under a prespecified interval-based criterion. That question differs from asking whether a conventional test detects a difference. The relevant evidence is the ratio of geometric means and the precision of that estimate, represented by its confidence interval relative to the 80-125% limits.

The registry record is informative about the intended design and the endpoint but incomplete for the primary statistical conclusion. It identifies randomization, double masking, parallel groups, a 1:1:1 allocation, and the AUC0-inf criterion. It also posts arm-level estimates and standard deviations. However, the ratio confidence intervals and the sponsor’s conclusion are not reported in the registry record. The distinction between descriptive summaries and the inferential quantities needed for a similarity decision is central to reading the results responsibly.

The three-arm setting also makes it important to know exactly which comparisons and decision rules were used. The registry record’s general objective refers to similarity among all three groups, but the complete contrast structure and any multiplicity strategy are not reported. Without those details, readers cannot determine the full testing framework or assess how the overall conclusion was reached.

More broadly, the record illustrates why analysis populations, missing-data handling, and planned sample-size justification matter alongside the headline outcome. The posted pharmacokinetic counts differ from the safety counts for TRS003, and the reason is not reported. These gaps limit how completely the posted summaries can be evaluated. Statistical interpretation depends not just on point estimates, but also on uncertainty, inclusion rules, and a clearly described analysis plan.

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 main limitation of the registry record for interpreting the primary objective is the absence of the ratio estimates and 90% confidence intervals required by the stated similarity criterion. The record gives the rule, but not the quantities needed to determine whether the rule was satisfied. It also does not post the sponsor’s conclusion for pharmacokinetic similarity.

Although arm-level AUC0-inf summaries are available, the TRS003 summary includes 34 participants, compared with 38 participants in each comparator group. The safety summaries list 38 participants at risk in each group. The registry record does not explain why these analysis counts differ or identify the analysis populations. Missing-data methods, exclusions, and the handling of incomplete pharmacokinetic profiles are not reported in the registry record.

The record does not describe the primary statistical model, covariates, transformations, assumptions, or methods for estimating the confidence intervals. It also does not report a sample-size justification, interim-analysis plan, or a multiplicity procedure. These absences prevent a full assessment of the precision and robustness of the intended inference. The sample-size planning illustration is not the trial’s own design justification and should not be treated as observed power.

Generalizability is limited by the study population and dosing context described in the record: healthy male participants receiving a single 3 mg/kg intravenous dose. The registry record does not establish how the findings apply to other populations, dosing schedules, or clinical outcomes. Secondary outcome analyses are not posted, and safety-event detail beyond the summarized counts is not reported in the registry record. These limitations constrain both statistical and clinical interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Compare Pharmacokinetic and Safety of TRS003 to China-approved Bevacizumab and US-licensed Avastin® — NCT03882424.
• Registry record last updated 2020-06-16; status last verified 2020-06.
• Results first posted 2020-06-16.
• 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

NCT03882424 is a completed, randomized, double-blind, parallel-group Phase 1 study sponsored by Zhejiang Teruisi Pharmaceutical Inc. It enrolled 114 healthy male participants and compared a single intravenous 3 mg/kg dose of TRS003 with China-approved bevacizumab and US-licensed Avastin, using 1:1:1 allocation.

The primary endpoint was AUC0-inf, with pharmacokinetic similarity defined by a 90% confidence interval for the ratio of geometric means within 80-125%. Posted group summaries include AUC0-inf estimates and standard deviations, but the ratio confidence intervals and primary conclusion are not reported in the registry record. Safety summaries report no serious adverse events and no deaths in any group; other adverse-event counts are also listed. The record posts no inferential analyses for the primary or secondary outcomes.