Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of GSK2330811 in Healthy Japanese Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of GSK2330811 in Healthy Japanese Participants (NCT04138043), a randomized phase 1 study. The primary outcome is Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, double-blind, placebo-controlled, parallel-group study at a single center. It enrolled healthy Japanese participants and evaluated a single subcutaneous dose of GSK2330811 against matching placebo. The registry describes the study as double-blind and sponsor-open. The planned allocation was approximately 7:3 between active treatment and placebo; the safety results list 7 participants at risk in the GSK2330811 group and 2 in the placebo group.

The active-treatment dose was 450 mg, given as three separate subcutaneous injections. The study was designed to assess safety and tolerability as well as pharmacokinetics, pharmacodynamics and immunogenicity. The primary safety outcome covered adverse events and serious adverse events through Day 126. Secondary outcomes included measures of plasma concentration and drug disposition, including maximum concentration, area under the concentration-time curve, apparent clearance, time to maximum concentration, terminal half-life and apparent volume of distribution at steady state. The registry also lists participants with positive anti-GSK2330811 antibodies.

The record lists enrollment of 9, a start date of 2019-12-05, primary completion on 2020-05-28 and completed status. The purpose and population make this a short early-stage evaluation of a single dose in healthy participants. It is not a trial of treatment outcomes in people with Crohn's disease or systemic sclerosis. Details such as the randomization sequence method, the exact concealment procedure, the planned follow-up schedule beyond the primary timeframe, and any dose-escalation procedure 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.

Before assignment: A total of 9 participants were randomized and enrolled in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population.

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 Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over Up to Day 126.

The primary endpoint is the number of participants with adverse events and serious adverse events, assessed through Day 126. An adverse event is defined in the registry as any untoward medical occurrence temporally associated with study intervention, whether or not it is considered related to that intervention. A serious adverse event is one meeting the registry's seriousness criteria, such as death, a life-threatening occurrence, inpatient hospitalization or its prolongation, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or another medically or scientifically serious situation.

Counting participants with events is a descriptive safety measure: it indicates how many people in each group experienced events during the defined follow-up. It is useful in an early-stage study because safety and tolerability are central questions after exposure to an investigational intervention. A participant count is not the same as an event count; one person may experience more than one event. The registry's primary outcome is explicitly participant-based, and it does not provide event-level detail in the reported figures summarized in the record.

The endpoint also does not by itself establish that an event was caused by treatment. The adverse-event definition includes occurrences whether or not judged related to the intervention. Interpretation therefore depends on the clinical descriptions, timing, severity and attribution of individual events, details that are not included in the posted primary outcome counts.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this? The primary measure is a count of participants who experienced adverse events or serious adverse events during follow-up. In general, a participant-based binary outcome classifies each participant according to whether the event occurred at least once. It differs from an event count, which can include repeated events for the same person, and from a rate, which accounts for person-time. The registry identifies participants as the unit and gives the assessment timeframe as up to Day 126.

The adverse-event definition includes untoward medical occurrences whether or not they are considered related to study intervention. The serious-event definition uses specified seriousness criteria. These are related but distinct classifications: the serious-event count captures events meeting seriousness criteria, while the other adverse-event count is reported separately. The posted results do not include event-level listings or a breakdown by severity, timing, duration or attribution. Those omissions limit what a count alone can convey about the clinical character of the safety experience.

How should the group counts be read?

The denominators are the participants at risk in each group: 2 for placebo and 7 for GSK2330811 450 mg. The record reports the number of participants with serious events and the number with other adverse events. These counts should be read with their group denominators rather than in isolation. General statistical principle: denominators are essential because a count has a different meaning in groups of different sizes. Here, the group sizes are small, so a change in the experience of even one participant would have a visible influence on the descriptive pattern.

A participant count does not reveal how many total events occurred. If a participant had more than one adverse event, the participant would still count once in a measure of participants with events. The registry outcome is defined as a number of participants; event-level frequency or recurrence cannot be inferred from it. Likewise, a count over the whole follow-up period does not show when events occurred or how long they lasted.

What does a confidence interval add?

General statistical explanation: a confidence interval describes the uncertainty around an estimate under a specified statistical method. A narrow interval indicates greater precision, while a wide interval indicates greater uncertainty. For a small safety population, estimates of event frequency can be imprecise, especially when few or no events are observed. No confidence interval for the primary outcome is reported in the registry record, so a numerical range of plausible values should not be inferred from the counts alone.

The registry also does not report a statistical test or a single comparison estimate for the primary endpoint. It states that the primary outcome has several categories or time points and is not reduced to one comparison. Thus, the posted evidence supports a descriptive account of observed counts, not a p-value-based conclusion about a difference between groups. No adjusted estimate is reported either.

How do the design features relate to interpretation?

Randomization assigns participants to groups by chance and is intended to reduce systematic differences in treatment assignment. Blinding can reduce the influence of expectations on participant experience or outcome assessment; the registry describes the study as double-blind and sponsor-open. These design features do not remove uncertainty caused by the small number of participants. Details of the randomization method, allocation concealment and any procedures used to maintain blinding are not reported in the registry record.

The sample-size assumptions describe a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation and a normal approximation. The illustration concerns detecting a stated fraction of the observed effect. It is not the trial's own design justification, and such planning calculations are not observed power. The record does not report the trial's sample-size justification. The registry entries do not include numerical planning results, so no sample-size value can be interpreted from them.

What is not available for statistical assessment?

The registry lists 19 outcome measures and 0 analyses. Numerical summaries for the listed pharmacokinetic and pharmacodynamic outcomes, the anti-GSK2330811 antibody outcome, and other outcome measures are not included in the registry record considered for this explanation. The statistical analysis plan, prespecified estimands, handling of missing observations, any interim analyses, and any multiplicity procedure are not reported in the registry record. Without those details, it is not possible to assess whether the posted counts represent all intended analyses or how any additional analyses were specified.

In general, methods should match the question and outcome structure. A participant-level safety count is naturally presented with the number at risk and the timeframe; a formal comparison would require an explicitly defined estimand and analysis method. Because the registry does not post that comparison, the sound statistical reading stays with the observed group counts and their limited precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures, including the primary safety measure and secondary pharmacokinetic, pharmacodynamic and immunogenicity outcomes. It reports 0 analyses in the information. A multiplicity procedure—such as an approach for interpreting many outcome tests together—is not reported in the registry record. The record also does not report whether a formal testing hierarchy or other prespecified strategy was used. Because no single primary-outcome comparison is posted, there is no inferential result to interpret as adjusted or unadjusted for multiple testing.

Missing-data handling is not reported in the registry record. The primary outcome timeframe is up to Day 126, but the registry entries do not describe whether all participants completed follow-up, how incomplete follow-up was handled, or how missing event information was classified. The at-risk counts identify participants included in the posted safety counts; they do not establish the completeness of every scheduled assessment. No imputation method or sensitivity analysis is reported.

The safety population is defined as all randomized participants who received at least one dose of study treatment. This is the analysis population described for the primary safety outcome. The registry does not report a separate intention-to-treat analysis, per-protocol population, or analysis population for each secondary outcome. It is also not reported whether any participants were excluded from analyses or why. These details matter because analysis-population definitions determine which participants contribute to a particular result.

These absences limit assessment of the analysis process; they do not change the descriptive fact that the registry records zero serious adverse events in either group. They do mean that the posted record does not support claims about the planned handling of multiplicity, incomplete data or alternative analysis populations.

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 serious adverse event figures are participant counts through Day 126. The registry records 0 of 2 participants with a serious adverse event in the placebo group and 0 of 7 in the GSK2330811 450 mg group. It also records 0 deaths in each group. These figures describe what was recorded in the safety population; they are not proof that the risk is zero.

The separate other-adverse-event counts are 2 of 2 for placebo and 6 of 7 for GSK2330811 450 mg. These counts are not a measure of the total number of events, because the outcome counts participants rather than repeated events. The registry information does not give the event descriptions, severity, timing, duration or treatment attribution needed to characterize those occurrences.

General statistical principle: when the number of participants is small, observed counts can be unstable indicators of the frequency that might occur in a larger population. A zero count in a small group is compatible with considerable uncertainty about uncommon events. No confidence intervals or formal comparison are reported for these figures, so the results should be read descriptively rather than as evidence of equal safety or a precise difference between groups.

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

The record documents a small randomized study of a single subcutaneous dose of GSK2330811 in healthy Japanese participants. For the primary safety outcome through Day 126, it records no serious adverse events and no deaths in either group. Other adverse events were recorded in both groups. These observations describe the participants included in the posted safety results; they do not establish how frequently events would occur in a larger or different population.

The results do not show that GSK2330811 is effective for Crohn's disease or systemic sclerosis. Participants were healthy volunteers, and the primary outcome was a safety count rather than a clinical disease outcome. Although the study aimed to assess pharmacokinetics, pharmacodynamics and immunogenicity, numerical results for those outcomes are not reported in the registry record. No conclusions about drug exposure, biological response or antibody findings can therefore be drawn from the safety counts.

The counts also do not demonstrate that the active treatment and placebo have equivalent safety. The placebo group contains 2 participants and the active-treatment group 7, and no confidence interval or formal primary-outcome comparison is posted. Randomization is a design strength, but a small sample limits precision and leaves substantial uncertainty about uncommon outcomes. The absence of recorded serious events in this study is not the same as evidence that such events cannot occur.

Finally, an adverse event is not necessarily caused by the intervention under the registry definition. The posted counts do not provide the clinical details needed to judge relatedness or seriousness for individual occurrences. The appropriate interpretation is therefore narrow: the record reports the observed participant counts in this study, while leaving the broader frequency, causal attribution and comparative safety questions unresolved.

13. Why This Trial Matters Statistically

This study illustrates an important distinction in early clinical research: a trial can be designed to characterize safety and drug behavior without providing a definitive estimate of comparative clinical benefit or harm. The primary outcome is a participant count of adverse events and serious adverse events through Day 126. The registry's stated aims also include pharmacokinetics, pharmacodynamics and immunogenicity, which address different questions from whether a treatment improves a disease outcome.

The small safety population makes precision a central issue. The record lists 2 participants at risk in the placebo group and 7 in the active-treatment group. A zero serious-event count in both groups is useful as a factual account of the observed experience, but cannot tightly characterize rare outcomes. A reader should distinguish the observed data from the broader uncertainty that remains when only a small number of people have been followed.

The record also makes clear why outcome definitions and analysis plans matter. A count of participants is not a count of all events, and the primary outcome has several categories or time points rather than a single posted comparison. No statistical comparison is reported. Without a defined inferential result, the data should not be converted into a claim that one group differs from the other.

Finally, the healthy-volunteer setting has a specific scope. It allows study of a single dose in the population enrolled, but does not directly answer questions about outcomes in people with the conditions named in the drug-development rationale. The statistical lesson is to keep conclusions aligned with the population, endpoint, follow-up and level of precision actually represented in the 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 safety population is very small and unequal between groups: 2 participants in the placebo group and 7 in the GSK2330811 450 mg group. That limits precision, particularly for serious or uncommon outcomes, and makes a formal comparison difficult to interpret even if one were available. No confidence intervals or primary-outcome comparison are reported in the registry record.

The enrolled population consisted of healthy Japanese participants. The findings therefore do not directly describe people with Crohn's disease or systemic sclerosis, conditions mentioned in the study rationale. The study evaluated a single dose, so the posted safety counts do not characterize repeated dosing or longer-term exposure. The primary safety timeframe is up to Day 126, and the registry entries do not provide further detail about event timing or the completeness of follow-up.

Event-level information is not available in the registry record. The record does not describe the specific other adverse events, their severity, duration, relationship to treatment or recurrence. It also does not provide numerical results for the listed pharmacokinetic, pharmacodynamic or immunogenicity outcomes. Consequently, the safety counts cannot be interpreted alongside detailed drug-exposure or biological-response results.

Further analysis details—including the sample-size justification, statistical analysis plan, missing-data methods, multiplicity strategy, randomization procedure and interim analyses—are not reported in the registry record. The record lists 19 outcome measures but 0 analyses and does not reduce the primary outcome to a single comparison. These limitations restrict both the precision of conclusions and assessment of how the analysis was planned and carried out.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of GSK2330811 in Healthy Japanese Participants — NCT04138043.
• Registry record last updated 2021-05-24; status last verified 2021-04.
• Results first posted 2021-05-24.
• 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

The registry record describes a completed, randomized, double-blind, placebo-controlled, parallel-group Phase 1 study in healthy Japanese participants. Total enrollment was 9. Participants received either a single 450 mg subcutaneous dose of GSK2330811, administered as three injections, or matching placebo. The study aimed to assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity.

The primary outcome counted participants with adverse events and serious adverse events through Day 126. The posted safety figures list no serious adverse events and no deaths in either group. Other adverse events were reported for 2 of 2 placebo participants and 6 of 7 GSK2330811 participants. The record lists 19 outcome measures and 0 analyses; it does not provide a single statistical comparison for the primary outcome. The study began on 2019-12-05, reached primary completion on 2020-05-28 and is listed as completed.