This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK2831781 After an Intravenous (IV) Dose in Healthy Japanese and Caucasian Subjects, and a Subcutaneous (SC) Dose in Healthy Caucasian Subjects (NCT03965533), a randomized phase 1 study. The primary outcome is Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03965533 |
| Phase | Phase 1 |
| Condition | Healthy Volunteers |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 36 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Healthy Japanese and Caucasian male participants took part. Part A studied Japanese and Caucasian participants receiving intravenous doses; Part B studied Caucasian participants receiving subcutaneous doses. The registry enrollment is 36, and the study description says approximately 36 participants were planned, with 16 in Part A and 20 in Part B.
Intervention
GSK2831781 was given as a single intravenous dose of 450 mg in Part A, or as a single subcutaneous dose of 150 mg or 450 mg in Part B. The registry describes GSK2831781 as a humanized, ADCC-enhanced depleting monoclonal antibody specific to LAG3.
Comparator
Participants were assigned to placebo groups. Intravenous placebo was used in Part A, with separate Caucasian and Japanese groups. Subcutaneous placebo was used in Part B; participants in the 150 mg subcutaneous group also received dummy saline injections to maintain blinding.
Primary question
The primary safety question was how many participants had serious adverse events (SAEs) or non-serious adverse events (non-SAEs) in Part A up to Day 112. The broader study also assessed safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity after administration of GSK2831781.
This is an early-phase study in healthy volunteers, rather than a trial designed to assess a clinical benefit in people with a disease. Its main purpose was to characterize the safety and tolerability of single doses and to measure how GSK2831781 behaved in the body and related to pharmacodynamic measures. The study included two routes of administration, but the routes were evaluated in separate parts and in different participant groups: Part A compared intravenous dose groups with intravenous placebo among Japanese and Caucasian participants, while Part B evaluated subcutaneous doses and placebo among Caucasian participants.
The primary endpoint is a count of participants with SAEs and non-SAEs, not a measure of symptom improvement or disease control. It therefore addresses the occurrence of adverse events during the stated follow-up, while the pharmacokinetic and pharmacodynamic outcomes address different questions about drug concentration and biological response. The registry does not report a single pooled treatment comparison or a numerical estimate of a treatment effect for the primary endpoint. Interpretation should remain focused on the descriptive safety record and on the limits of the group sizes and reported analyses.
3. Trial Design
The registry identifies NCT03965533 as a completed, randomized, double-blind, placebo-controlled, parallel-group Phase I study sponsored by GlaxoSmithKline. It was planned as two parts, with single-dose administration in healthy participants. The registry records an enrollment of 36; the study description says approximately 36 participants would be enrolled, with 16 in Part A and 20 in Part B. The start date was 2019-06-10 and primary completion was 2019-12-10.
Part A studied a single intravenous infusion of 450 mg GSK2831781 or intravenous saline placebo in Caucasian and Japanese male participants. The groups listed in the safety results include 6 participants in each active-dose group and 2 in each corresponding placebo group. Part B studied Caucasian male participants assigned to subcutaneous placebo, 150 mg GSK2831781 or 450 mg GSK2831781. The 150 mg group received a drug injection plus two dummy saline injections, and the 450 mg group received three drug injections. The safety results list 4 participants in the placebo group and 8 in each active-dose group.
Random assignment is intended to reduce systematic differences between groups, while masking can limit the influence of treatment knowledge on participant or investigator reporting. The registry identifies the study as double-blind, but further details about the masking procedures are not reported in the registry record. A parallel-group design means participants were assigned to a group rather than being described as receiving each regimen in turn. The study duration is described as approximately 147 days for each participant. The primary safety endpoint covers Part A through Day 112; the corresponding primary-outcome timeframe for Part B is not reported in the registry record.
Because the intravenous and subcutaneous regimens were studied in separate parts, and the participant groups differ by ancestry, route and dose, comparisons should be interpreted within their study context. The registry does not describe a randomized head-to-head comparison of every route and dose in a common population. Details of the allocation sequence, stratification, or any other design restrictions 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 30 participants were screened and 16 participants were enrolled in Part A (14 were screen failures). A total of 41 participants were screened and 20 participants were enrolled in Part B (21 were screen failures). Placebo arms across similar dosing strategies were combined in Part B.
Only the first 6 of 7 groups are shown.
Part A (112 Days)
| Stage | Part A: Placebo IV- Caucasian Participants | Part A: GSK2831781 450 mg IV- Caucasian Participants | Part A: Placebo IV- Japanese Participants | Part A: GSK2831781 450 mg IV- Japanese Participants | Part B: Placebo SC | Part B: GSK2831781 150 mg SC |
|---|---|---|---|---|---|---|
| STARTED | 2 | 6 | 2 | 6 | 0 | 0 |
| COMPLETED | 2 | 6 | 2 | 6 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Part B (112 Days)
| Stage | Part A: Placebo IV- Caucasian Participants | Part A: GSK2831781 450 mg IV- Caucasian Participants | Part A: Placebo IV- Japanese Participants | Part A: GSK2831781 450 mg IV- Japanese Participants | Part B: Placebo SC | Part B: GSK2831781 150 mg SC |
|---|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 | 4 | 8 |
| COMPLETED | 0 | 0 | 0 | 0 | 4 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Population comprised of all randomized (all participants who were randomized into the study and received a randomization number) participants who received 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 8 groups are shown.
| Characteristic | Unit | Part A: Placebo IV- Caucasian Participants | Part A: GSK2831781 450 mg IV- Caucasian Participants | Part A: Placebo IV- Japanese Participants | Part A: GSK2831781 450 mg IV- Japanese Participants | Part B: Placebo SC | Part B: GSK2831781 150 mg SC |
|---|---|---|---|---|---|---|---|
| Participants analysed | 2 | 6 | 2 | 6 | 4 | 8 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 6 | 2 | 6 | 4 | 8 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 2 | 6 | 2 | 6 | 4 | 8 |
| Race/Ethnicity, Customized: White-White/Caucasian/European Heritage (H) | Participants | 2 | 6 | 0 | 0 | 4 | 8 |
| Race/Ethnicity, Customized: Asian-Japanese H/East Asian H/South East Asian H | Participants | 0 | 0 | 2 | 6 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs), measured over Up to Day 112.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with serious adverse events and non-serious adverse events in Part A, with follow-up stated as up to Day 112. An adverse event is defined in the registry as an untoward medical occurrence temporally associated with use of a medicinal product, whether or not it is considered related to that product. An SAE includes events meeting the registry’s specified seriousness criteria, such as death, a life-threatening event, hospitalization or its prolongation, disability or incapacity, a congenital anomaly or birth defect, or another situation judged serious by a physician.
The endpoint is used to describe safety and tolerability: it records how many participants experienced events, rather than the total number of event episodes or a measure of clinical benefit. Counting participants avoids treating repeated events in one person as though they came from separate participants. The registry presents serious and non-serious events as distinct categories, which matters because seriousness is a classification based on consequences and clinical criteria, not simply how often an event occurs.
The named primary endpoint applies to Part A, whereas the adverse-event results also list groups in Part B. These Part B counts provide additional descriptive safety information but do not change the stated primary endpoint’s Part A scope. The registry reports a safety population comprising randomized participants who received study intervention. It does not report a formal hypothesis, a prespecified comparative estimand, or a statistical test for this endpoint in the registry record. Thus, the count data describe events within the listed groups; they do not alone establish whether a group difference is meaningful or attributable to treatment.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results are descriptive counts across seven groups. For SAEs, the registry reports zero affected participants in both intravenous placebo groups, both intravenous 450 mg groups and the subcutaneous placebo and 450 mg groups. In the subcutaneous 150 mg group, 1 of 8 participants was reported with an SAE. The registry reports zero deaths in every listed group. These figures describe the observed record during the reported safety follow-up; they should not be read as evidence that serious events cannot occur in other participants or settings.
For non-SAEs, the reported affected-participant counts are 2 of 2 for Caucasian intravenous placebo, 5 of 6 for Caucasian intravenous 450 mg, 0 of 2 for Japanese intravenous placebo, 4 of 6 for Japanese intravenous 450 mg, 4 of 4 for subcutaneous placebo, 6 of 8 for subcutaneous 150 mg, and 4 of 8 for subcutaneous 450 mg. These are counts of participants affected, not counts of individual event episodes. The registry’s overall primary endpoint specifies Part A, so Part B figures should be understood as additional safety information rather than as part of that primary endpoint’s stated scope.
The group sizes are small, ranging from 2 to 8 participants in the listed groups. With groups of this size, a single participant changes the observed count noticeably, and an absence of reported events is not a precise estimate of the risk in a broader population. The registry does not report confidence intervals or a formal between-group test for these counts. It also does not give the complete event-level details needed to understand timing, recurrence, duration or attribution for each event. The top serious-event term is listed as Tonsillitis, 12.5%; the registry record does not provide enough context in the stated outcome information to interpret that term as a comparative rate or link it to a particular group.
The study includes different populations, routes and doses. For that reason, apparent differences across the group counts cannot be isolated as an effect of dose or route without a relevant analysis and an appropriate comparison. The Caucasian intravenous and subcutaneous groups are in different parts, and Japanese participants appear only in Part A. The registry does not report an adjusted analysis accounting for these design features. No quantitative conclusion about a treatment effect should be inferred from the raw event counts alone.
Pharmacokinetic and pharmacodynamic outcomes are listed in the registry, including concentration measures and a relationship between LAG3-positive T-cell levels and plasma concentrations. Numerical results for those outcomes, along with formal comparative estimates for safety, are not reported in the registry record. Consequently, the posted information supports a description of recorded event counts, but not a precise estimate of comparative safety or a conclusion about pharmacological effects.
9. Statistical Methods Explained
Randomization assigns participants to study groups by chance. In general, this approach aims to reduce systematic differences between groups at enrollment, so that a comparison is less vulnerable to deliberate or predictable assignment. The registry identifies the study as randomized but does not report details of the sequence-generation method, allocation concealment, stratification or block size. Those features therefore cannot be evaluated from the registry record.
Double masking means that more than one specified study role is kept unaware of the assigned intervention, which can reduce the influence of treatment expectations on care or outcome reporting. The registry labels the study double-blind and describes dummy saline injections in the subcutaneous 150 mg group, an approach intended to maintain blinding across injection procedures. The identities of the masked roles and the procedures for maintaining or assessing masking are not reported in the registry record. A parallel-group design assigns participants to a group for the study rather than describing a crossover in which the same participants receive multiple regimens.
The primary safety outcome is a count of participants with events. In general, a participant-level count answers how many people experienced at least one event in a category during the defined observation period. It differs from an event count, which could count repeated occurrences in the same person more than once. The registry defines the safety population as all randomized participants who received study intervention. The group-specific numbers at risk are shown with the safety results, but details of any exclusions after randomization or the handling of participants with incomplete follow-up are not reported in the registry record.
What does a confidence interval communicate?
In general, a confidence interval describes statistical uncertainty around an estimated quantity under the assumptions of the method used. Wider intervals indicate less precision, while narrower intervals indicate greater precision. The registry record does not report confidence intervals for the primary safety counts, so the precision of comparative safety estimates cannot be assessed from those results. Counts alone can be especially limited when the groups contain few participants, because the observed data may change substantially with only a small change in the number of affected people.
What can a comparison establish?
A comparative analysis requires a defined contrast, such as the difference in event frequency between two groups, and a statistical method suited to the outcome and design. The registry record does not report a formal comparative estimate or test for the primary endpoint. The record also does not specify an analysis plan for adjustment across population, route or dose. The result listing should therefore be read as descriptive rather than as a confirmatory test of a treatment difference. The registry identifies zero serious events in most groups and one in the subcutaneous 150 mg group, but the small group sizes and absence of an inferential analysis limit what can be concluded about underlying event rates.
How should the planning illustrations be read?
General sample-size calculations use assumptions about the effect to be detected, the type I error rate, allocation and the statistical model. The registry’s planning description states a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the target effect expressed as a fraction of the observed effect. These are planning assumptions, not observed findings and not evidence that the study had a particular power to detect a difference. The registry does not report the original trial’s sample-size justification or state that its design was based on these planning illustrations. Numerical planning estimates are not reported in the registry record. Such illustrations should be treated as hypothetical planning aids, not as a substitute for the trial’s actual design rationale or analysis.
General concepts about over-dispersion are more relevant to count outcomes that vary more than a chosen probability model expects. Over-dispersion can make standard errors too small if a model assumes less variability than the data contain. The primary safety endpoint is reported as participants with events, not as an event-rate model with a stated distribution. The registry does not report a model-based analysis of these counts, so it is not possible to say whether over-dispersion was assessed or whether any adjustment was used.
The registry lists pharmacokinetic measures including area under the concentration-time curve, maximum observed concentration and time to maximum concentration. In general, these characterize exposure and the timing of peak concentration; bioavailability compares the extent of systemic availability across routes. Pharmacodynamic measures address biological changes associated with drug exposure. The registry also lists a degradation-rate measure derived from the relationship between LAG3-positive T-cell levels in blood and plasma concentrations. The numerical results and analysis details for these listed outcomes are not reported in the registry record. Therefore, no conclusion about their magnitude, precision or statistical significance can be drawn from the listed outcome names alone.
10. Multiplicity, Missing Data and Analysis Populations
The study lists numerous secondary outcomes across Parts A and B, including concentration-time measures, bioavailability, and a pharmacodynamic degradation-rate measure. In general, when several outcomes or contrasts are tested, the chance of at least one apparently unusual result can increase unless the analysis plan addresses multiplicity. The registry record does not report a multiplicity strategy, a hierarchy of confirmatory outcomes, or the number of hypotheses tested. It also does not report statistical analysis results for these secondary outcomes. The primary safety endpoint is itself reported as two categories, SAEs and non-SAEs, and the registry does not provide a formal test for either category.
Missing-data handling can affect interpretation when participants do not complete follow-up or measurements are unavailable. The registry defines the safety population as randomized participants who received study intervention, but does not report the number with missing safety follow-up, the completeness of each outcome, or any imputation or censoring approach. It is therefore not possible to assess whether missing observations could have affected the reported counts or the listed pharmacokinetic and pharmacodynamic measures.
The primary endpoint is specified for Part A through Day 112. The safety counts also include Part B groups, but the registry does not state an equivalent primary endpoint timeframe for Part B. The record does not report a detailed statistical analysis plan, a prespecified handling of protocol deviations, or a detailed account of analysis populations for outcomes beyond safety. Those aspects are not reported in the registry record and should not be inferred from the outcome listings.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Part A: Placebo IV- Caucasian Participants | 0 | 2 | 0.0% |
| Part A: GSK2831781 450 mg IV- Caucasian Participants | 0 | 6 | 0.0% |
| Part A: Placebo IV- Japanese Participants | 0 | 2 | 0.0% |
| Part A: GSK2831781 450 mg IV- Japanese Participants | 0 | 6 | 0.0% |
| Part B: Placebo SC | 0 | 4 | 0.0% |
| Part B: GSK2831781 150 mg SC | 1 | 8 | 12.5% |
| Part B: GSK2831781 450 mg SC | 0 | 8 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Part A: Placebo IV- Caucasian Participants | 0 of 2 |
| Part A: GSK2831781 450 mg IV- Caucasian Participants | 0 of 6 |
| Part A: Placebo IV- Japanese Participants | 0 of 2 |
| Part A: GSK2831781 450 mg IV- Japanese Participants | 0 of 6 |
| Part B: Placebo SC | 0 of 4 |
| Part B: GSK2831781 150 mg SC | 0 of 8 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Part A: Placebo IV- Caucasian Participants | 2 of 2 |
| Part A: GSK2831781 450 mg IV- Caucasian Participants | 5 of 6 |
| Part A: Placebo IV- Japanese Participants | 0 of 2 |
| Part A: GSK2831781 450 mg IV- Japanese Participants | 4 of 6 |
| Part B: Placebo SC | 4 of 4 |
| Part B: GSK2831781 150 mg SC | 6 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Part A: Placebo IV- Caucasian Participants | Part A: GSK2831781 450 mg IV- Caucasian Participants | Part A: Placebo IV- Japanese Participants | Part A: GSK2831781 450 mg IV- Japanese Participants | Part B: Placebo SC | Part B: GSK2831781 150 mg SC |
|---|---|---|---|---|---|---|---|
| Tonsillitis | Infections and infestations | 0 of 2 | 0 of 6 | 0 of 2 | 0 of 6 | 0 of 4 | 1 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Part A: Placebo IV- Caucasian Participants | Part A: GSK2831781 450 mg IV- Caucasian Participants | Part A: Placebo IV- Japanese Participants | Part A: GSK2831781 450 mg IV- Japanese Participants | Part B: Placebo SC | Part B: GSK2831781 150 mg SC |
|---|---|---|---|---|---|---|---|
| Headache | Nervous system disorders | 1 of 2 | 2 of 6 | 0 of 2 | 2 of 6 | 0 of 4 | 1 of 8 |
| Nasopharyngitis | Infections and infestations | 0 of 2 | 2 of 6 | 0 of 2 | 1 of 6 | 0 of 4 | 2 of 8 |
| Cough | Respiratory, thoracic and mediastinal disorders | 0 of 2 | 2 of 6 | 0 of 2 | 0 of 6 | 0 of 4 | 1 of 8 |
| Injection site bruising | General disorders | 0 of 2 | 0 of 6 | 0 of 2 | 2 of 6 | 0 of 4 | 0 of 8 |
| Vessel puncture site bruise | General disorders | 0 of 2 | 0 of 6 | 0 of 2 | 1 of 6 | 1 of 4 | 0 of 8 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 0 of 2 | 1 of 6 | 0 of 2 | 0 of 6 | 0 of 4 | 1 of 8 |
| Catheter site bruise | General disorders | 0 of 2 | 1 of 6 | 0 of 2 | 0 of 6 | 0 of 4 | 0 of 8 |
| Fatigue | General disorders | 0 of 2 | 1 of 6 | 0 of 2 | 0 of 6 | 0 of 4 | 0 of 8 |
| Injection site erythema | General disorders | 0 of 2 | 0 of 6 | 0 of 2 | 1 of 6 | 0 of 4 | 0 of 8 |
| Paraesthesia | Nervous system disorders | 0 of 2 | 1 of 6 | 0 of 2 | 0 of 6 | 0 of 4 | 0 of 8 |
Serious events with the highest arm-level rate: tonsillitis (12.5%).
The serious-adverse-event figures are participant counts. The registry reports no participants with an SAE in the two intravenous placebo groups, either intravenous 450 mg group, the subcutaneous placebo group or the subcutaneous 450 mg group. It reports 1 of 8 participants with an SAE in the subcutaneous 150 mg group. Deaths are reported as zero in every group. These values describe the events recorded in this study; they do not show that the risk is zero beyond the observed participants and follow-up.
Non-serious events are listed separately. The registry reports 2 of 2 affected in Caucasian intravenous placebo, 5 of 6 in Caucasian intravenous 450 mg, 0 of 2 in Japanese intravenous placebo, 4 of 6 in Japanese intravenous 450 mg, 4 of 4 in subcutaneous placebo, 6 of 8 in subcutaneous 150 mg and 4 of 8 in subcutaneous 450 mg. A participant is counted as affected in a category; the figures do not indicate how many separate episodes occurred or whether events were judged related to treatment.
The record lists Tonsillitis, 12.5%, as the top serious-event term. Further context about the term and its group-level distribution is not reported in the registry record. Small group sizes, the difference between the study parts and the lack of formal comparative estimates mean these figures should be read as descriptive safety observations, not as a ranking of treatments.
12. What the Result Does, and Does Not, Mean
The results mean that the registry records adverse events among participants in a small, randomized, double-blind, placebo-controlled Phase I study of single doses of GSK2831781. For the listed serious events, one participant in the subcutaneous 150 mg group was affected, while no affected participants were reported in the other listed groups; no deaths were reported. Non-serious events were reported in several groups, with the group-specific participant counts stated in the safety results. The study also planned to assess pharmacokinetic, pharmacodynamic and immunogenicity outcomes.
These observations do not establish that an event was caused by GSK2831781. The registry’s AE definition includes events whether or not they are considered related to the medicinal product, and the posted counts do not provide a full attribution analysis. Nor do the counts establish that one route or dose is safer than another. Groups were small, and the routes and participant populations were not all studied in the same part or in the same groups. The record does not provide a formal comparative safety estimate, confidence interval or test.
The findings also do not demonstrate a clinical benefit. Participants were healthy volunteers, and the primary outcome was a safety count rather than a disease outcome. Pharmacokinetic and pharmacodynamic outcomes are listed, but their numerical results are not reported in the registry record. The record therefore does not support conclusions about drug exposure, biological response or the relationship between exposure and safety.
In general, early-phase studies help describe initial safety and characterize how a compound behaves under the study conditions. They are not, by themselves, evidence that an intervention is effective or that uncommon harms have been ruled out. The interpretation of this study is bounded by its single-dose design, the specified healthy volunteer groups and the information made available in the registry. Conclusions beyond those observed counts and design features would require evidence not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how an early-phase safety study answers a different question from a trial designed to estimate clinical benefit. Its primary endpoint is a participant count for serious and non-serious adverse events, while its secondary outcomes cover drug concentration, timing, bioavailability and a pharmacodynamic relationship. Those outcomes require different summaries and analyses; the names of the outcomes alone do not reveal their numerical results or precision.
The design combines two study parts and more than one administration route, with Japanese and Caucasian groups in Part A and Caucasian groups in Part B. This structure is relevant when interpreting comparisons: a difference between groups may coincide with differences in route, dose or participant group. Statistical interpretation depends on the comparison actually defined and analyzed, not simply on reading across all listed groups. The registry does not report an adjusted comparative analysis that separates those factors.
The recorded group sizes are small, which makes descriptive safety counts useful for documenting what was observed but limited for estimating uncommon events precisely. Reporting the denominators alongside event counts is essential to understanding the scale of the evidence. The registry’s lack of confidence intervals and formal tests also highlights why raw counts should not be turned into claims of comparative certainty.
Finally, the record lists multiple secondary outcomes, yet does not report a multiplicity plan or numerical analysis results for them. This illustrates an important distinction between a study’s measurement scope and the evidence available to interpret each measure. Clear outcome definitions, analysis populations, missing-data methods and prespecified comparisons are all important to judging statistical strength; several of those details are not reported 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 safety groups are small: the listed numbers at risk range from 2 to 8 participants. As a result, the counts provide limited precision for describing event occurrence, particularly for serious events. The registry does not report confidence intervals or a formal comparative analysis of the primary safety endpoint, so uncertainty around group differences cannot be quantified from the posted outcome information.
The study has separate intravenous and subcutaneous parts, and the participant composition differs across them. Japanese participants are included in Part A, while Part B includes Caucasian participants. A comparison across parts would therefore involve more than a route or dose difference. The registry does not report an analysis designed to disentangle these factors. The listed 150 mg and 450 mg subcutaneous groups also have different group sizes from the subcutaneous placebo group.
The primary endpoint is defined for Part A through Day 112, while safety counts are listed for Part B as well. A Part B primary safety timeframe is not reported in the registry record. Complete event-level information, including timing, recurrence, duration and attribution, is not reported with the stated counts. The registry gives a top serious-event term but does not provide enough context in the outcome information to interpret its distribution across groups.
Although pharmacokinetic and pharmacodynamic outcomes are listed, their numerical results and analysis methods are not reported in the registry record. The record also does not report the trial’s original sample-size justification, detailed statistical analysis plan, multiplicity strategy, missing-data approach, allocation method or masking procedures beyond its double-blind designation. These omissions limit evaluation of precision, bias and robustness. The results should therefore be interpreted as a registry-level description of a small early-phase study, not as a complete account of all statistical analyses or event details.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK2831781 After an Intravenous (IV) Dose in Healthy Japanese and Caucasian Subjects, and a Subcutaneous (SC) Dose in Healthy Caucasian Subjects — NCT03965533.
- Registry record last updated 2020-11-18; status last verified 2020-09.
- Results first posted 2020-11-18.
- 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.
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18. Record Summary
NCT03965533 is a completed, randomized, double-blind, placebo-controlled, parallel-group Phase I study of GSK2831781 in healthy Japanese and Caucasian male participants. Part A evaluated a single intravenous dose of 450 mg and intravenous placebo in Japanese and Caucasian groups; Part B evaluated subcutaneous placebo and single doses of 150 mg or 450 mg in Caucasian participants. The registry records enrollment of 36 and describes approximately 147 days of study participation per participant.
The primary endpoint was the number of Part A participants with SAEs and non-SAEs through Day 112. The registry reports one participant with an SAE in the subcutaneous 150 mg group, none in the other listed groups, and no deaths. Non-serious event counts are reported by group. Formal comparative estimates, confidence intervals, numerical pharmacokinetic and pharmacodynamic results, and detailed statistical analysis methods are not reported in the registry record. The event counts are descriptive and should be interpreted in light of the small groups and distinct study parts.