Safety, Tolerability and Pharmacokinetic Investigation of GSK3882347 in Healthy Participants.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability and Pharmacokinetic Investigation of GSK3882347 in Healthy Participants. (NCT04488770), a randomized phase 1 study. The primary outcome is Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, placebo-controlled phase 1 study with a crossover model. The registry describes a two-part design: a single-ascending-dose phase (SAD) and a multiple-ascending-dose phase (MAD). Its title identifies an investigation of safety, tolerability, pharmacokinetics, and food effect. The study is recorded as completed, with enrollment of 61 and dates from 2020-08-24 to primary completion on 2021-05-14.

In Part 1, participants in two cohorts were assigned to receive GSK3882347 or matching placebo. The active-dose schedules included 50 mg, 150 mg, and 250 mg in one cohort, and 500 mg, 900 mg, and 15 mg in the other, across the listed periods. The registry describes a maximum of four periods for each cohort. A food-effect evaluation was to take place in Period 4 of only one cohort, with selection based on observed human pharmacokinetics.

Part 2 evaluated repeated oral dosing across planned cohorts. The listed active doses were 50 mg, 150 mg, 500 mg, and 900 mg, with placebo groups also described. Dosing was planned from Day 1 to Day 7. Some Part 2 doses are described as projected and dependent on pharmacokinetic or pharmacodynamic findings from preceding cohorts; the dose in the 50 mg cohort could also be changed in light of safety, tolerability, and pharmacokinetic findings in Part 1.

The registry gives allocation ratios of 3:1 for active treatment to placebo in Part 1 and 4:1 in Part 2. It also describes the study as double-blind (sponsor-unblinded). More detail about the crossover sequence, washout periods, or how the sequence was incorporated into analyses 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: A total of 61 participants (21 participants in Part 1 and 40 participants in Part 2) were enrolled in the study.

Only the first 6 of 13 groups are shown.

Part 1-Cohort 1: Period 1 (Up to 5 Days)

Reasons for not completing this period:

Part 1-Cohort 1: Period 2 (Up to 5 Days)

Part 1-Cohort 1: Period 3 (Up to 5 Days)

Reasons for not completing this period:

Part 1-Cohort 1: Period 4 (Up to 5 Days)

Analysis population for the primary outcome, as defined in the registry: Safety Population comprised of all participants who received at least one dose of study intervention.

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.

Only the first 6 of 14 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over Up to 3 months.

The primary outcome is the number of Part 1 participants with non-serious adverse events and serious adverse events, with a timeframe of up to 3 months. An adverse event is defined in the registry as an untoward medical occurrence temporally associated with use of a study intervention, regardless of whether it is considered related to that intervention. A serious adverse event is defined by criteria that include death, a life-threatening event, inpatient hospitalization or its prolongation, persistent disability or incapacity, a congenital anomaly or birth defect, or another medically or scientifically important event.

The endpoint is a participant count, rather than a measure of event severity, duration, or frequency per person. The registry also says that common non-serious adverse events meeting its stated threshold are presented. The primary outcome is used to describe safety and tolerability in this early-phase investigation: counting affected participants can show whether events were recorded in each dose group during the stated observation period.

Counts alone do not establish that an event was caused by treatment. The registry definition explicitly includes events regardless of assessed relationship to the intervention. Nor do participant counts, by themselves, provide a controlled estimate of comparative risk or a precise estimate of uncommon harms. The record does not report a primary hypothesis test or a prespecified method for comparing these counts.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

For a binary safety outcome, each participant is classified according to whether the outcome was recorded. A count is the number of participants in a group who meet that definition. It is not a count of all event episodes: a participant with more than one event can still contribute to the participant count as an affected participant. This is a general explanation of binary outcomes. The registry states that the primary endpoint is a participant count and defines the safety population as all participants who received at least one dose of study intervention.

Why distinguish serious from non-serious events?

The registry uses a clinical definition of seriousness, including outcomes such as death, life-threatening events, hospitalization, persistent disability, congenital anomalies, and other medically important events. Seriousness is not the same as whether an event was judged related to study intervention. The primary outcome covers both serious and non-serious adverse events, while the posted group data report these categories separately. These distinctions allow readers to see what was recorded under each classification without implying causation.

What can group counts tell readers?

Counts are useful for a descriptive account of how many participants in each regimen had an event. They can help identify where events were recorded and make the group-level safety record legible. Counts do not, on their own, adjust for differences in follow-up, exposure, or cohort characteristics. They also do not express the uncertainty around an event rate. A confidence interval is a general statistical tool for conveying the range of values compatible with data and a specified method; confidence intervals for the safety outcomes are not reported in the registry record.

Because the counts concern participants, they should not be interpreted as event rates per unit of exposure or as a comparison of event burden. Such measures would require information and analysis beyond the participant counts. The registry does not report a primary inferential comparison, adjusted or otherwise, for these event counts. The appropriate reading is therefore descriptive.

Why does the study structure matter?

The registry describes a crossover model, single-dose periods, and repeated-dose cohorts. It also records randomization and double masking, with sponsor unblinding. General statistical interpretation depends on how treatment sequence, period, and cohort are handled. In a crossover design, observations from the same participant can be related, and period or sequence effects may matter; this is a general consideration, not a claim about analyses performed in this trial. The registry record does not report the crossover sequence details, washout information, or an analysis model that accounts for repeated observations or periods.

Part 1 and Part 2 also address different dosing schedules. Part 1 evaluates single doses, while Part 2 evaluates repeated doses over the stated dosing days. The dose descriptions include planned changes contingent on earlier safety, tolerability, and pharmacokinetic or pharmacodynamic findings. Thus, regimen counts should be read in their cohort and study-part context rather than treated as a dose-response analysis. The registry does not report a formal model for dose-response or a statistical plan for comparing dose levels.

What do the planning assumptions mean?

The stated planning illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These are assumptions for an illustration, not evidence that the trial was designed using them. A sample-size illustration describes how a hypothetical future comparison might be planned under assumptions; it is not observed power and does not establish that this trial had adequate power for a particular safety comparison. The registry record does not report the trial’s own sample-size justification or the effect size used in its original design.

For a binary outcome, any planning calculation also depends on assumptions about the outcome frequency and the planned comparison. No further inputs or calculation results are reported in the registry record. These assumptions cannot be used to infer the study’s intended inferential analysis, and the posted safety counts should not be converted into a claim of observed power.

What can be said about pharmacokinetic methods?

The listed secondary outcomes indicate that the study was designed to assess concentration-time summaries, plasma concentrations at a specified time, apparent oral clearance and volume of distribution, mean residence time, and dose proportionality. In general, pharmacokinetic summaries describe drug concentration and exposure over time; they answer different questions from the binary safety endpoint. The registry lists these outcomes, but numerical pharmacokinetic results and detailed analysis methods are not reported in the registry record. The planned food-effect assessment is described as dependent on observed human pharmacokinetics, but its results are not available in the registry record for this analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and multiple secondary pharmacokinetic outcomes across the single-dose and repeated-dose parts. When several outcomes, doses, or comparisons are examined, the chance of at least one apparently unusual result can rise if each is tested separately without accounting for multiplicity. This is a general statistical concern, not a statement that a particular adjustment was or was not used in the trial. A multiplicity strategy is not reported in the registry record.

The record does not report a statistical analysis plan, the hierarchy of secondary outcomes, or which inferential tests were intended. It also does not report interim analyses or stopping rules. Their absence from the registry record should not be read as proof that none were used; their status is not reported in the registry record.

The safety population is defined as participants who received at least one dose of study intervention. That definition identifies who is included in the safety assessment, but it does not explain how missing outcome data, withdrawals, or incomplete follow-up were handled. Missing-data methods, the number of participants with unavailable endpoint information, and reasons for missingness are not reported in the registry record. For safety outcomes, incomplete observation can matter because a participant needs an opportunity for an event to be recorded.

The registry reports different allocation ratios in the two study parts and a crossover model. It does not describe how those features were handled in statistical analyses, or how the analysis population was defined for pharmacokinetic outcomes. Therefore, the posted safety counts can be read as registry-reported descriptive results, but a fuller assessment of missingness, multiplicity, and analysis choices is not possible from the record details available.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures are participant counts, separated by regimen. In the posted results, the serious adverse event count is zero for every listed Part 1 and Part 2 group, and the death count is also zero for every listed group. These figures describe the events recorded during the study; they do not establish that the underlying risk is zero or rule out events that are uncommon.

The denominators reported for each group are the participants at risk in that group. They should be interpreted within each regimen and study part. Part 1 includes single-dose regimens and a fed regimen, while Part 2 includes repeated-dose regimens. The groups are not a single uniform comparison, and the registry does not report an inferential test comparing serious adverse event counts.

Non-serious adverse events were recorded in the groups, with participant counts varying by regimen. The primary outcome description notes that common non-serious adverse events meeting its stated threshold are presented, but specific event terms are not included in the registry record for this interpretation. As the registry defines adverse events regardless of whether they are considered related to study intervention, the counts should not be read as treatment-caused events. They are a descriptive account of safety observations in this study.

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

The registry record documents a randomized, double-blind, placebo-controlled phase 1 investigation of GSK3882347 in healthy participants. It describes single-dose escalation, repeated dosing, a planned food-effect evaluation, and assessment of safety, tolerability, and pharmacokinetics. The primary safety endpoint counts participants with non-serious and serious adverse events in Part 1. The posted serious adverse event and death counts are zero in each listed group, while non-serious adverse events are recorded.

These findings describe what was recorded in the study groups; they do not establish that GSK3882347 caused or prevented any reported event. The adverse event definition includes occurrences whether or not considered related to intervention. The registry record does not provide a formal statistical comparison of these counts, confidence intervals, or detailed event terms for the non-serious events in the registry record for this interpretation. The numerical safety record therefore does not support a precise estimate of comparative risk.

The findings also do not answer whether the intervention benefits people with urinary tract infections. Participants are described as healthy adults, and the study’s focus was early-phase safety, tolerability, and pharmacokinetics. A condition listed in a registry record does not transform a healthy-participant pharmacology study into an efficacy trial in people with that condition.

The results do not establish the full safety profile across broader populations, longer exposure, or uncommon events. Nor do the safety counts reveal the pharmacokinetic results: although those outcomes are listed, their numerical results are not reported in the registry record. The appropriate interpretation is limited to the recorded study design and descriptive safety results, with uncertainty remaining about conclusions the registry does not report.

13. Why This Trial Matters Statistically

This trial illustrates how early-phase studies can combine safety monitoring with pharmacokinetic objectives. The registry describes both single-dose escalation and repeated dosing, alongside a food-effect evaluation and dose proportionality assessment. These aims are related but distinct: safety outcomes count affected participants, while pharmacokinetic outcomes characterize concentration and exposure. Keeping those questions separate prevents safety counts from being mistaken for evidence about drug exposure or clinical benefit.

The design also demonstrates why cohort context matters. Dose decisions in the repeated-dose part were described as dependent on findings from preceding cohorts, and the food-effect evaluation was contingent on observed pharmacokinetics. These features make the study’s progression informative as a development design, but they also mean dose groups should not automatically be treated as exchangeable arms in a simple comparative analysis.

For biostatistical interpretation, the record highlights the difference between descriptive safety evidence and inferential evidence. A zero serious adverse event count is a direct description of what was recorded, but without uncertainty intervals or a reported analysis plan it does not precisely characterize the probability of uncommon harm. Similarly, participant counts for non-serious events do not by themselves establish causality or a dose-response relationship.

The trial is therefore useful as an example of the limits of registry-level interpretation. The record conveys the intended design and outcome definitions, but leaves analysis details, missing-data handling, and numerical pharmacokinetic results unreported. Recognizing both the information available and what remains unreported is central to reading early-phase trial evidence carefully.

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 gives a broad description of the design, but several details needed for a fuller statistical assessment are not reported. These include the crossover sequence and washout details, the statistical analysis plan, planned comparisons, handling of period or sequence effects, and methods for missing data. The registry also does not report a sample-size justification, interim analyses, or stopping rules.

The primary outcome is a participant count, and the registry entries available for this interpretation do not include confidence intervals or formal comparative estimates. The outcome definition covers adverse events regardless of their relationship to intervention; specific non-serious event terms and event-level details are not included. Consequently, the counts cannot establish causation, severity patterns among non-serious events, or a precise comparative safety effect.

The study enrolled healthy participants and was designed as a phase 1 investigation. Its safety observations may not describe outcomes in people with urinary tract infections or in populations outside the stated healthy-participant group. The listed pharmacokinetic outcomes and planned food-effect assessment are not accompanied by numerical results in the registry record. Conclusions about exposure, dose proportionality, or food effect are therefore unavailable.

The registry describes projected repeated-dose regimens and dose decisions contingent on preceding findings. The available record does not give the detailed rationale or analysis underlying those decisions. In addition, the existence of a crossover model and allocation ratios does not by itself establish how the data were analyzed. These limitations constrain interpretation to the design descriptions and the reported descriptive safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Tolerability and Pharmacokinetic Investigation of GSK3882347 in Healthy Participants. — NCT04488770.
• Registry record last updated 2023-02-17; status last verified 2022-05.
• Results first posted 2023-02-17.
• 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

NCT04488770 is a completed, randomized, double-blind phase 1 study sponsored by GlaxoSmithKline. Enrollment was 61, with study start on 2020-08-24 and primary completion on 2021-05-14. The registry describes a placebo-controlled, two-part investigation in healthy adult men and women of non-childbearing potential.

Part 1 assessed single ascending doses, with a planned food-effect evaluation; Part 2 assessed repeated doses. The primary outcome counted Part 1 participants with non-serious and serious adverse events over up to 3 months. No serious adverse events or deaths are recorded in the listed groups. Non-serious adverse event counts are reported by regimen.

The study also listed pharmacokinetic outcomes, but numerical results for those outcomes are not reported in the registry record. Analysis-plan details, missing-data methods, and multiplicity handling are likewise not reported.