Phase 1, Single and Repeat Dose Study to Assess Safety, Tolerability, and Pharmacokinetics (PK) of GSK3923868 in Participants With Chronic Obstructive Pulmonary Disease (COPD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1, Single and Repeat Dose Study to Assess Safety, Tolerability, and Pharmacokinetics (PK) of GSK3923868 in Participants With Chronic Obstructive Pulmonary Disease (COPD) (NCT05677347), a randomized phase 1 study. The primary outcome is Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) Following Single Dose of GSK3923868.

2. Clinical Question

In statistical terms, the main focus is event frequency in a small early-phase study, rather than an efficacy comparison. The registry lists pharmacokinetic outcomes as secondary outcomes, including measures of plasma concentration after single and repeat dosing. The primary outcome is a participant count, not a time-to-event measure or a continuous measure of symptom change. Although the crossover structure allows participants to receive different treatments across periods, the posted adverse-event counts are grouped by treatment exposure. The registry record does not report a formal statistical comparison that accounts for the crossover design.

3. Trial Design

This was a Phase 1, randomized, double-blind, placebo-controlled crossover study of inhaled GSK3923868 in participants with COPD. The registry reports enrollment of 12 participants and a completed study. The study started on 2023-01-23, and primary completion was recorded as 2023-07-20.

The study had two parts. The first was a single ascending dose part assessing two dose levels of GSK3923868 or placebo across treatment periods 1 and 2 in a single cohort. The registry summary describes a washout period of a minimum of 5 days after each treatment period. The second part assessed repeat dosing of one dose level of GSK3923868 or placebo in treatment period 3, in the same cohort, with up to 14 days of follow-up. The stated participation durations for treatment periods 1, 2, and 3 were 6, 6, and up to 29 days, respectively, including follow-up for treatment period 3.

The listed treatment sequences combine single-dose exposure to 500 mcg, single-dose exposure to 1000 mcg, placebo single dosing, repeat-dose exposure to 1500 mcg, and placebo repeat dosing. The sequence descriptions indicate that participants could receive active treatment in some periods and placebo in others. Some sequence descriptions in the registry record are incomplete, so details beyond the listed sequence names and the stated study summary are not reported in the registry record.

A crossover design differs from a parallel-group design because treatment exposure is organized across periods within a cohort. That structure can be useful when outcomes are observed under more than one exposure condition, but interpretation may depend on period effects, washout, and the analysis approach. The statistical methods used to address those features are not reported in the registry record. Randomization and double blinding are reported, but the method of sequence generation, concealment, and maintenance of masking is 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: All the 12 participants were enrolled and randomized in the study.

Treatment Period 1 (3 Days)

Washout Period 1 (up to 6 Days)

Treatment Period 2 (3 Days)

Washout Period 2 (up to 6 Days)

Analysis population for the primary outcome, as defined in the registry: This analysis was performed on Safety Population which included all participants who received at least 1 dose of study treatment.

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 Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) Following Single Dose of GSK3923868, measured over Up to 18 days.

The primary endpoint counts participants who experienced non-serious adverse events (non-SAEs) and serious adverse events (SAEs) following single-dose GSK3923868. The stated timeframe is up to 18 days. The registry defines an adverse event as an untoward medical occurrence temporally associated with use of a study intervention, whether or not it is considered related to that intervention. Serious events include occurrences meeting the registry's seriousness criteria, such as death, life-threatening events, inpatient hospitalization or prolonged hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or another situation judged serious on medical or scientific grounds. Events not meeting the serious classification are considered non-serious.

A participant count is a direct way to describe how many people in a treatment group had at least one event of the specified category. It is useful in a safety study because it makes the observed frequency of events visible without treating every event as a separate participant. The count alone does not describe event severity within the non-serious category, timing, duration, recurrence, or causal relationship to treatment. Those details are not reported in the registry record.

The analysis population is described as the safety population, including all participants who received at least one dose of study treatment. The posted adverse-event figures include both single-dose (SD) and repeat-dose (RD) exposure groups, while the primary outcome title refers to events following single dose. The record does not report a statistical model or a formal treatment comparison for this outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a count of participants with adverse events. For this type of outcome, the basic descriptive information is the number of participants with an event and the number at risk in the exposure group. The posted figures give both quantities for non-serious and serious events. General statistical explanation: a count communicates the observed frequency, while the denominator indicates the group in which those events were assessed. Neither quantity alone conveys uncertainty as fully as an interval estimate would.

What does a participant count represent?

A participant count is different from a count of all event episodes. If one participant experiences more than one event, a participant-based outcome generally counts that person once for the specified category, whereas an event-based outcome could count multiple occurrences. The registry describes the primary endpoint as the number of participants with non-SAEs and SAEs. It does not report whether repeated events or event terms were separately summarized in the posted outcome details. The safety figures therefore should be read as participant counts, not as a complete account of every adverse-event episode.

Seriousness and relatedness are also distinct concepts. Seriousness is determined by the event's consequences or clinical criteria stated in the registry definition. Relatedness concerns whether the event is considered associated with study treatment. The registry's adverse-event definition includes events whether or not they are considered related. The posted counts do not, by themselves, classify events as treatment-related.

Why does the crossover structure matter?

In a crossover design, treatment is administered across periods rather than being limited to separate groups throughout the study. This can mean observations from different periods are linked because they arise from the same participant. General statistical explanation: observations from the same person may be correlated, so treating them as fully independent can misstate uncertainty. Period effects, sequence effects, and residual effects from an earlier treatment may also matter in crossover studies. The registry reports a washout period of a minimum of 5 days after each treatment period in the single-dose part, but it does not report analyses of carryover, period, or sequence effects.

The posted adverse-event groups have different numbers at risk, and the record does not explain the reasons for those differences. It also does not provide participant-level overlap across treatment exposures. Therefore, the group counts should not be interpreted as independent parallel-arm samples or used to reconstruct a crossover analysis. The inferential approach, if any, is not reported in the registry record.

What can be inferred from zero serious-event counts?

A zero count is an observation, not a guarantee of zero underlying risk. General statistical explanation: when an event is uncommon, a study with limited exposure may observe no events even if the event remains possible. The precision of a zero count depends on the amount and duration of observation, as well as the analysis assumptions. No confidence interval or other uncertainty estimate for the serious-event counts is reported in the registry record. The data should therefore be described as no serious events reported in the listed groups, without claiming that serious events are ruled out.

Likewise, raw non-serious event counts do not establish a comparative effect. A formal comparison would need to specify the estimand, account for the crossover structure, and describe how missing observations and exposure time are handled. Those methods are not reported in the registry record. The outcome is a participant count, and the registry does not report an exposure-adjusted event rate or a model-based estimate.

What does the record say about precision and analysis?

The registry lists 16 outcome measures and zero analyses. No inferential analysis details, confidence intervals, or hypothesis tests are reported for the primary endpoint. General statistical explanation: an interval estimate describes a range of values compatible with the data under a specified method, while a hypothesis test assesses data against a particular null model. Without either reported, the posted counts support descriptive interpretation but not a quantified claim about the precision of a treatment contrast.

The registry identifies pharmacokinetic secondary outcomes, including area under the plasma-concentration time curve and maximum observed plasma concentration and time to maximum concentration, for single and repeat dosing. The outcome list does not give numerical pharmacokinetic results in the information available for this analysis. No interpretation of those outcomes can be made from their names alone.

General statistical explanation: over-dispersion is relevant when a model assumes that variability follows a particular count distribution but the observed variability is larger than that assumption allows. In that situation, uncertainty estimates from a simple model can be too small. The posted primary outcome is a participant count, and no count model or dispersion parameter is reported in the registry record. Over-dispersion therefore cannot be assessed from the information posted for this outcome.

There is also no reported statistical analysis plan, sample-size justification, or interim-analysis information. Those omissions limit assessment of whether the analysis followed prespecified methods, how precision was anticipated, and whether any planned monitoring could have affected interpretation. They do not alter the descriptive counts, but they restrict the conclusions that can be drawn from them.

10. Multiplicity, Missing Data and Analysis Populations

The study lists several outcomes, including the primary adverse-event measure and secondary pharmacokinetic measures. The registry record does not report a multiplicity strategy, such as a hierarchy of hypotheses or an adjustment for testing multiple outcomes. Because no inferential analyses are reported for the primary endpoint, the posted counts should be treated descriptively rather than as results from a family of formal significance tests. The record does not report whether multiplicity was addressed in a separate statistical analysis plan.

Missing-data handling is not reported in the registry record. The safety population is defined as participants who received at least one dose of study treatment, but the record does not describe completeness of adverse-event follow-up, how withdrawals were handled, or whether any participants had incomplete observation. The primary endpoint timeframe is up to 18 days; details of observation by participant and exposure are not reported.

The registry describes a crossover study and gives exposure-specific numbers at risk, but it does not report the analysis population for each treatment period beyond the general safety-population definition. It does not explain whether participants with partial treatment-period data were included in particular exposure summaries, nor how within-participant dependence was handled. These gaps mean the denominators and counts can be read as posted, but cannot be used to reconstruct an adjusted comparison or a complete-data analysis.

The record does not report an analysis plan, imputation approach, sensitivity analysis, or interim analysis. Their use or absence cannot be inferred. The lack of this information limits evaluation of how missing observations, multiple outcomes, and crossover features were incorporated into statistical inference.

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 by exposure group. The record reports 0 serious adverse events among 6 at risk for placebo single dose, 0 among 9 at risk for GSK3923868 500 mcg single dose, 0 among 9 at risk for GSK3923868 1000 mcg single dose, 0 among 3 at risk for placebo repeat dose, and 0 among 9 at risk for GSK3923868 1500 mcg repeat dose. The listed death count is 0 in every group.

These are observed counts, not estimates of the probability of a serious event in a broader population. The number at risk and the study's observation period matter when interpreting a zero count. The primary endpoint timeframe is up to 18 days, while the study summary describes follow-up of up to 14 days in the repeat-dose part. The record does not provide event-level timing or a formal uncertainty estimate for the group counts.

For non-serious adverse events, the record reports 1 among 6 at risk for placebo single dose, 2 among 9 for GSK3923868 500 mcg single dose, 1 among 9 for GSK3923868 1000 mcg single dose, 2 among 3 for placebo repeat dose, and 4 among 9 for GSK3923868 1500 mcg repeat dose. The counts are descriptive and do not establish causality or a treatment difference. Because this is a crossover study, exposure groups should not automatically be treated as independent comparison arms.

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

The results establish a limited descriptive point: the registry reports no serious adverse events or deaths in the listed single-dose and repeat-dose exposure groups, and it reports non-serious adverse-event counts for each group. Those observations provide a record of events during this study's exposure and follow-up context. They are not a formal estimate of comparative safety, and no inferential analysis is reported.

The results do not show whether GSK3923868 caused the non-serious events. The registry's definition includes adverse events whether or not they are considered related to the intervention, and event-specific relatedness information is not reported. Nor do the counts provide detail about event type, severity within the non-serious category, duration, recurrence, or clinical course.

The zero serious-event counts should not be interpreted as proof that serious events are impossible. The study enrolled 12 participants, and the numbers at risk differ by exposure group. A small early-phase study can describe what was observed in its participants but cannot, from zero events alone, establish the absence of uncommon risks. No confidence intervals or other uncertainty measures are reported for these counts.

The study's crossover structure also limits simple comparisons. Participants may contribute observations across more than one treatment period, so treatment-group counts may not represent independent groups of people. The registry does not report a model accounting for repeated observations, nor does it describe analyses of period or carryover effects. Raw differences in counts therefore should not be treated as a treatment effect.

The record identifies pharmacokinetic outcomes, but their numerical results are not reported in the information available for this analysis. The adverse-event data also do not answer questions about clinical benefit. Overall, the posted information supports a descriptive account of reported safety events and the study design, while leaving comparative effects, precision, causality, and broader generalizability unresolved.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the limits and uses of early-phase safety data. Its primary endpoint is a participant count, which offers a straightforward description of observed adverse events. Counts are useful for conveying what occurred within each exposure group, particularly when the study is focused on safety and tolerability rather than a definitive efficacy comparison.

At the same time, the study illustrates why design and analysis context matter. It is a randomized, double-blind crossover study, and the registry lists different numbers at risk across treatment exposures. Participants may contribute observations during more than one period, so a raw count by exposure does not automatically produce an independent-group comparison. Appropriate interpretation depends on whether the analysis accounts for the repeated, within-participant structure; the registry record does not report such an analysis.

The zero serious-event counts also demonstrate the distinction between an observed result and a precise estimate of risk. No serious events were reported in the listed groups, but the record does not include uncertainty intervals or an inferential analysis. The observation is relevant to the study's safety description, yet it cannot alone rule out uncommon events or establish comparative safety.

Finally, this record shows how much context is needed to interpret even simple outcomes. The primary endpoint definition, exposure-specific denominators, follow-up descriptions, and crossover design all shape what can be concluded. Missing information about event details, analysis methods, missing data, and multiplicity prevents a more complete statistical evaluation. The study can therefore be read as a descriptive early-phase safety assessment, not as a conclusive comparison of treatment risks.

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 registry record contains limited detail for evaluating the adverse-event results. It reports group-level counts but does not provide event-level terms, timing, duration, recurrence, severity within the non-serious category, or relatedness to treatment. The record also does not explain the differences in the numbers at risk across exposure groups.

The crossover design creates an additional interpretive constraint. The record does not identify participant-level overlap across treatment periods or report a statistical method that accounts for within-participant correlation. It also does not report analysis of period, sequence, or carryover effects. Although a washout period of a minimum of 5 days is described after each single-dose treatment period, the registry does not report the statistical assessment of whether washout was sufficient for the outcomes studied.

Other limitations include the absence of reported confidence intervals, hypothesis tests, an analysis plan, missing-data methods, and a multiplicity strategy. The registry defines the safety population but does not report follow-up completeness by exposure. It lists pharmacokinetic outcomes without numerical results in the information available for this analysis. Some treatment-sequence descriptions are incomplete, and the registry does not report further participant characteristics or a sample-size justification. These gaps restrict assessment of precision, representativeness, and the robustness of comparisons.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase 1, Single and Repeat Dose Study to Assess Safety, Tolerability, and Pharmacokinetics (PK) of GSK3923868 in Participants With Chronic Obstructive Pulmonary Disease (COPD) — NCT05677347.
• Registry record last updated 2024-10-15; status last verified 2024-07.
• Results first posted 2024-10-15.
• 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

NCT05677347 is a completed Phase 1 randomized, double-blind, placebo-controlled crossover study of inhaled GSK3923868 in participants with COPD. The registry reports enrollment of 12 participants, a start date of 2023-01-23, and primary completion on 2023-07-20. The study had a single ascending dose part followed by a repeat-dose part.

The primary outcome was the number of participants with non-serious and serious adverse events following single-dose GSK3923868, with a timeframe of up to 18 days. The posted exposure-group figures report no serious adverse events or deaths and give non-serious adverse-event counts for single-dose and repeat-dose exposure groups. The registry identifies pharmacokinetic secondary outcomes but does not report numerical results for them in the information available for this analysis.

The record does not report inferential analyses, confidence intervals, missing-data methods, or a multiplicity strategy. The results therefore support descriptive interpretation of the posted safety counts, not a formal comparative conclusion.