A Study of Single Ascending Doses of PF-07258669 in Healthy Adult Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Single Ascending Doses of PF-07258669 in Healthy Adult Participants (NCT04628793), a randomized phase 1 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events (TEAEs).

2. Clinical Question

The study was designed as an early clinical evaluation in healthy adults, rather than as a comparison of clinical benefit in people with a disease. Its primary outcome was the number of participants with TEAEs. The registry also names pharmacokinetic outcomes: maximum observed concentration, area under the plasma concentration-time profile through the last quantifiable concentration, area under the profile extrapolated to infinite time, time to maximum concentration, and terminal half-life.

The intervention was administered as single doses in a sequential study. The registry describes three cohorts, each with three PF-07258669 doses and one placebo dose within the cohort. The listed adverse-event results are organized by dose group and pooled placebo. How the listed dose groups map onto the cohorts is not reported in the registry record.

The question addressed is therefore primarily descriptive: what adverse events were recorded, and what pharmacokinetic measurements followed dosing? A comparative estimate of efficacy is not reported in the registry record, and the study's stated population and outcomes do not establish effects in patients with a medical condition.

3. Trial Design

This was a randomized, double-blind, sponsor-open, placebo-controlled, first-in-human Phase 1 study of single ascending oral doses of PF-07258669. The registry identifies the study model as sequential. The sponsor was Pfizer. The study is recorded as completed, with a start date of 2021-03-16 and primary completion date of 2021-08-25.

The registry describes three cohorts. Within each cohort, participants were to receive three doses of PF-07258669 and one dose of placebo. The adverse-event results list pooled placebo and PF-07258669 dose groups from 0.1mg through 300mg. The record does not specify which dose groups belonged to which cohort, or provide further details about dose escalation decisions or the timing between cohorts.

Enrollment was 29. The safety analysis set included participants who were randomly assigned to study intervention and received a dose. This definition means the stated safety population excludes anyone randomized who did not receive intervention, if there were any such participants; whether that occurred is not reported in the registry record.

The primary outcome was the number of participants with TEAEs over the period from the first dose on Day 1 through telephone follow-up 28-35 days after the last dose, described as approximately up to 20 weeks. A TEAE was defined as an adverse event absent before treatment or one that worsened after treatment. The registry also lists pharmacokinetic outcomes, including measures of concentration, exposure over time, time to peak concentration, and terminal half-life.

Randomization and placebo control provide a framework for describing events across intervention groups, while the sequential design organizes the ascending-dose evaluation. The registry record does not report the randomization procedure, the details of masking, or a formal statistical analysis plan. It also does not report a sample-size justification.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety analysis set included all participants randomly assigned to study intervention and who received a 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.

Population: All randomized participants who received a dose of study intervention

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events (TEAEs), measured over From first dose of study intervention (Day 1) to telephone Follow Up (28-35 days after lase dose of study intervention) (approximately up to 20 weeks).

The primary endpoint is the number of participants with treatment-emergent adverse events. An adverse event was defined as an untoward medical occurrence temporally associated with study intervention, whether or not investigators considered it related to that intervention. A TEAE was an event that was absent before treatment or worsened after treatment, occurring from first dose through follow-up.

Counting participants with an event is a descriptive way to report how many people experienced one or more events during the defined observation period. It differs from counting every event: a participant with several events can still contribute once to a count of participants with TEAEs. The registry's primary outcome is expressed as a participant count, and the posted adverse-event results distinguish serious from other adverse events.

In an early study, this kind of safety endpoint helps characterize events observed after exposure and supports continued evaluation of tolerability. It does not by itself establish that an event was caused by the study drug. The registry definition explicitly allows events to be counted regardless of whether they were considered related to intervention; investigators assessed potential treatment relationship using clinical judgment.

The endpoint is not a measure of treatment benefit, and it does not summarize the severity, duration, or clinical importance of every event. Serious adverse events are reported separately using the registry's stated criteria, which include death, life-threatening events, hospitalization, persistent disability, congenital anomaly or birth defect, and other important medical events. The registry record does not provide a detailed event-by-event narrative in the listed results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The reported safety endpoint is a count of participants with treatment-emergent adverse events. Counts are directly interpretable as the number of people recorded with an event in each group. They are not event rates per unit of time, and they do not indicate how many separate events occurred. The registry also reports the number of participants at risk in each group, which gives the group size corresponding to each count.

What does a confidence interval add?

In general, a confidence interval describes the uncertainty around an estimated quantity under a specified statistical method. For an event count or event proportion, it can show how much uncertainty remains when the number of observed participants is limited. A narrow interval indicates greater precision than a wide one, though interpretation also depends on the quantity being estimated and the method used. Confidence intervals for the adverse-event results are not reported in the registry record, so precision cannot be assessed from interval estimates.

Why are descriptive counts not a treatment comparison?

Counts across groups provide a direct description of observed events, but a formal comparison requires a defined estimand and statistical method. For example, analyses might compare event proportions or model outcomes while accounting for relevant design features. The registry does not report such a model or comparison. In general, randomization can support comparisons by reducing systematic differences in expectation, but small groups can still have chance imbalances, and descriptive counts alone do not show whether an observed contrast is compatible with chance variation.

What is the role of the sequential design?

In general, a sequential ascending-dose design evaluates dose groups in an ordered process, with study conduct organized across cohorts. This can be useful in early development when safety and pharmacokinetic information are being gathered at increasing doses. The registry identifies a sequential model and describes three cohorts, but details of dose escalation decisions, stopping rules, and decision criteria are not reported in the registry record. Those details should not be inferred from the order of the listed dose groups.

How should the planning illustration be read?

The registry describes a planning illustration computed from the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Such calculations are illustrations for planning, not evidence that the study was designed with that sample size, and not observed power. The registry record does not report a sample-size justification for this trial. A planning estimate also depends on its assumptions; it does not guarantee that a future study will achieve a particular precision or result.

In general, over-dispersion matters when the variability in observed outcomes is greater than a model assumes. A model that understates variability can produce intervals that are too narrow and tests that are too confident. This issue is more commonly relevant to event counts than to a simple binary indicator of whether each participant had an event. The registry does not report a count model, an over-dispersion assessment, or model-based estimates for the adverse-event endpoint.

The record lists ten outcome measures and no analyses. The pharmacokinetic outcomes are named, but numerical estimates and their uncertainty are not reported in the registry record. The registry record also does not report a prespecified multiplicity procedure, missing-data method, or statistical analysis plan. Without those details and analysis results, the appropriate reading is descriptive: the reported counts show recorded events by group, but do not provide adjusted estimates or formal evidence for between-group differences.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and several secondary pharmacokinetic outcomes, while the record reports ten outcome measures in total. When a study evaluates multiple outcomes or performs multiple comparisons, the chance of at least one apparently noteworthy result can increase. In general, multiplicity procedures define how that issue is handled, for example by controlling an overall error rate or by designating analyses as exploratory. A multiplicity strategy is not reported in the registry record. No formal analyses are listed, so there are no reported multiplicity-adjusted or unadjusted inferential results to interpret.

The safety analysis set is defined as all participants randomly assigned to study intervention who received a dose. The registry does not report the number excluded from that set, if any, or the handling of participants with incomplete follow-up. It also does not report how missing adverse-event information or missing pharmacokinetic measurements were handled. In general, missingness can affect interpretation when the chance that data are missing is related to participants' health or their outcomes; the direction and size of any effect depend on the circumstances.

The record does not describe imputation, sensitivity analyses, or a separate intention-to-treat analysis population. These methods and populations should not be assumed. The reported adverse-event counts are therefore best read within the stated safety analysis set and the follow-up period defined for the endpoint, without assuming that missing observations were treated in a particular way.

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 registry reports 0 serious adverse events in pooled placebo and 0 in each listed PF-07258669 dose group. It also reports 0 deaths in every group. The group sizes range from 5 to 18 participants, as reported for the listed groups. These figures describe what was recorded during the study's safety follow-up; they do not establish that serious events or deaths could not occur.

A serious adverse event was defined using criteria that include death, a life-threatening event, inpatient hospitalization or prolongation of hospitalization, persistent disability or incapacity, congenital anomaly or birth defect, and certain other important medical events. A serious event is distinct from an event's assessed relationship to treatment: the registry says investigators used clinical judgment to assess potential relationship.

The absence of recorded serious events in these groups should be interpreted in the context of a small early-phase study. Such a study can describe observed safety findings but may not detect uncommon harms. The registry record does not report confidence intervals or additional detail on monitoring, event adjudication, or serious-event follow-up beyond the stated endpoint period.

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

The posted results describe adverse events observed after single doses of PF-07258669 in healthy adult participants and report no serious adverse events or deaths in the listed groups. Other adverse-event counts are reported separately for pooled placebo and each dose group. These observations are relevant to the study's stated purpose of evaluating safety, tolerability, and pharmacokinetics in a first-in-human setting.

The results do not establish that PF-07258669 caused any particular event. The registry defines adverse events as occurrences temporally associated with intervention, whether or not they were judged related, and notes that investigators used clinical judgment to assess potential relationship. Counts alone do not separate events caused by intervention from those that would have occurred otherwise.

The findings also do not establish that the treatment is effective or ineffective. This study enrolled healthy adults and its primary outcome was safety-related; an efficacy outcome is not reported in the registry record. Nor do the counts show that risk is absent. Small groups provide limited information about uncommon events, and the registry does not report uncertainty intervals or formal statistical comparisons.

Pharmacokinetic outcomes are named in the record, but numerical results for those measures are not reported in the registry record. Therefore, no conclusion about concentration, exposure, peak timing, or half-life can be drawn from the listed adverse-event counts. The appropriate scope of interpretation is limited to the recorded safety observations and the study's design and outcome definitions.

13. Why This Trial Matters Statistically

This trial is statistically notable as a first-in-human, randomized, placebo-controlled evaluation that combines safety monitoring with pharmacokinetic outcomes. In early clinical research, the questions are often descriptive: what events are observed after exposure, and what concentration-time measurements are recorded? Such questions differ from estimating a treatment effect on a clinical outcome in a patient population.

The sequential structure and ascending dose groups create a setting where interpretation depends on dose, cohort, and the timing of observations. The registry describes the cohort structure and lists multiple dose groups, but does not report the mapping of those groups to cohorts or the decision rules for escalation. Recognizing those omissions prevents readers from treating the dose list as a complete account of the conduct or analysis.

The safety counts also illustrate why group size matters. Individual event counts are easy to read, but small groups offer limited precision, especially for uncommon outcomes. A zero count is an observation, not proof of no risk. Conversely, a higher count in one group does not by itself show a dose effect or causal relationship. Formal estimates and uncertainty measures would be needed to characterize comparative evidence, and these are not reported in the registry record.

Finally, the study demonstrates the value of separating what a registry records from what a statistical analysis can establish. The adverse-event counts give a descriptive account for this study; they do not replace detailed pharmacokinetic reporting, an analysis plan, or longer and larger evaluations. The registry record supports a bounded interpretation of these early observations rather than broad generalization.

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 provides adverse-event counts by group but does not report confidence intervals, hypothesis tests, adjusted comparisons, or a statistical model. This limits assessment of the precision of group-specific findings and of any differences between PF-07258669 and pooled placebo. The record lists no analyses, and formal statistical methods for the primary endpoint are not reported in the registry record.

Enrollment was 29, with group sizes of 5 to 18 in the listed adverse-event results. These limited group sizes constrain how much can be learned about uncommon events. The lack of reported serious events is therefore not evidence that such events are impossible or that risks are fully characterized.

The registry describes three cohorts and the allocation pattern within a cohort, but does not explain how the listed dose groups correspond to cohorts. Dose-escalation criteria, stopping rules, and the details of randomization are not reported in the registry record. The record labels the study double-blind and sponsor-open, but does not provide further details of who was masked or how masking was maintained.

Missing-data handling, the number of randomized participants who may not have received intervention, and completeness of follow-up are not reported in the registry record. The safety analysis set is defined, but the record does not describe sensitivity analyses or other analysis populations. Event-level descriptions, treatment-related event counts, and numerical pharmacokinetic results are also not reported in the registry record for this account. These gaps limit interpretation to the aggregate safety counts and the stated study design.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Single Ascending Doses of PF-07258669 in Healthy Adult Participants — NCT04628793.
• Registry record last updated 2024-02-21; status last verified 2023-07.
• Results first posted 2024-02-21.
• 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

NCT04628793 is a completed Phase 1 randomized, double-blind, sponsor-open, placebo-controlled, sequential, first-in-human study of single ascending oral doses of PF-07258669 in healthy adult participants. The registry reports enrollment of 29 and identifies Pfizer as the sponsor. The study start date was 2021-03-16, and the primary completion date was 2021-08-25.

The primary outcome was the number of participants with TEAEs from first dose through telephone follow-up 28-35 days after the last dose, described as approximately up to 20 weeks. The listed adverse-event results report no serious adverse events or deaths in pooled placebo or any PF-07258669 dose group. Other adverse-event counts are reported by group. The record names pharmacokinetic outcomes, but does not report numerical pharmacokinetic findings or formal analyses in the registry record for this account.