A First in Human Study to Evaluate Safety, Tolerability, and Pharmacology of PF-06826647 in Healthy Subjects and Subjects With Plaque Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A First in Human Study to Evaluate Safety, Tolerability, and Pharmacology of PF-06826647 in Healthy Subjects and Subjects With Plaque Psoriasis (NCT03210961), a randomized phase 1 study. The primary outcome is Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Single Ascending Dose [SAD] Period).

2. Clinical Question

3. Trial Design

NCT03210961 is described as a phase 1, randomized, quadruple-masked, sequential study with parallel groups. Its official title characterizes it as a within-cohort, placebo-controlled, single- and multiple-dose escalation study. It evaluated PF-06826647 in healthy subjects and subjects with plaque psoriasis. The registry lists an enrollment of 109 and a completed status.

The study began on 2017-07-14, with primary completion on 2019-01-25. The listed interventions include PF-06826647 tablet, PF-06826647 oral suspension, placebo tablet, and placebo oral solution or suspension. The record does not give further details in the arm descriptions, including specific allocation counts or how particular doses mapped to each formulation.

The trial had several aims: safety, tolerability, pharmacokinetics, and pharmacodynamics. Its listed secondary outcomes include plasma concentration measures such as AUCinf, AUC24, AUClast, Cmax, and Tmax, including dose-normalized versions for some measures. Those outcomes address drug exposure and its time course, rather than the primary vital-sign count. The registry lists 63 outcome measures overall.

The primary endpoint was limited to healthy participants in the single-ascending-dose period. The endpoint population excluded multiple-ascending-dose and psoriasis-cohort data. Accordingly, the endpoint does not represent every cohort enrolled in the study, nor does its stated population support conclusions about psoriasis outcomes.

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 208 potential participants were screened after signing an informed consent form, of whom 109 participants were randomized to receive study treatment.

Only the first 6 of 15 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population included the healthy participants who received study treatment and who had the safety parameters in the SAD Period. MAD and Psoriasis Cohorts data were not included.

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 enrolled participants who received at least 1 dose of study medication.

Only the first 6 of 16 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Single Ascending Dose [SAD] Period), measured over Baseline up to Day 8.

The primary endpoint counted participants whose vital-sign measurements met prespecified categorical criteria during the single-ascending-dose period, from baseline up to Day 8. It covered maximum absolute values and changes from baseline in supine systolic blood pressure, supine diastolic blood pressure, and supine pulse rate. The registry says these measurements were summarized descriptively by treatment and that participant counts meeting the criteria were provided.

A threshold-based count is used in safety monitoring to flag measurements that cross criteria chosen in advance. In general, this type of endpoint can make clinically relevant extremes easier to describe than a group average alone, while retaining the number of participants who met the criteria. It does not show the size or pattern of every measurement change, and the result depends on the particular thresholds and counting rules.

The registry does not state the criteria thresholds, the counts by treatment, or a statistical comparison for this endpoint. It also gives no primary endpoint result in the posted analyses. The endpoint therefore identifies what was intended to be counted, but the registry record does not permit a numerical account of how often participants met the criteria.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary endpoint is a count of participants meeting prespecified vital-sign criteria. In general, a count answers how many people met a defined condition, whereas a continuous summary describes a measurement on its original scale, such as blood pressure or pulse rate. A count can be useful for detecting how often a threshold was crossed, but it does not convey how far values were from the threshold or describe all measurements in the group. The registry does not report the thresholds or endpoint counts.

Why does the analysis population matter?

The registry defines the primary analysis population as healthy participants who received study treatment and had safety parameters in the single-ascending-dose period. Multiple-ascending-dose and psoriasis-cohort data were not included. An analysis population specifies which participants contribute to a particular result; it is not necessarily the same as the full enrollment. In general, comparing endpoints across different populations can be misleading when eligibility, treatment exposure, or measurement schedules differ. Results for this primary endpoint, if reported, would therefore apply to the specified healthy-participant cohorts rather than automatically to every enrolled participant.

What does descriptive analysis tell the reader?

The endpoint description says maximum absolute values and changes from baseline were summarized descriptively by treatment, and numbers meeting categorical criteria were provided. Descriptive summaries characterize the observed data without, by themselves, establishing a treatment effect or statistical significance. A count by treatment group can show the observed frequency, but interpretation also depends on group size, the criteria definition, and uncertainty. The registry record does not report endpoint group counts or an inferential comparison.

What can randomization and masking contribute?

The trial is listed as randomized and quadruple-masked, and its official title describes placebo control and parallel groups. In general, randomization aims to reduce systematic differences between treatment groups at assignment, while masking can limit the influence of treatment knowledge on participant, clinician, or assessment behavior. These design features do not guarantee that groups are identical or remove all sources of bias. The registry does not describe the allocation sequence, concealment procedures, or which roles were included in the masking designation beyond the quadruple label.

How should dose escalation be understood?

The study title describes single- and multiple-dose escalation. In general, escalation studies examine successive dose cohorts and are structured to gather information as exposure changes. The registry labels the model sequential and also describes parallel groups; it does not report the escalation rules, stopping criteria, or decision process for moving between dose levels. Those details are not reported in the registry record and should not be inferred from the dose names alone.

What do pharmacokinetic measures describe?

The listed secondary outcomes include AUCinf, AUC24, AUClast, Cmax, and Tmax, along with dose-normalized AUCinf, AUClast, and Cmax measures. In general, area-under-the-curve measures describe overall drug concentration over a specified time interval, Cmax is the maximum measured concentration, and Tmax is the time at which that maximum occurs. Dose normalization expresses an exposure measure relative to dose. These concepts describe exposure, not clinical benefit. The registry record does not report the numerical results for these outcomes.

What do the planning illustrations mean?

The record describes planning illustrations based on a fraction of an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. In general, such calculations estimate the sample size associated with a stated design and assumed effect; they do not describe the trial's actual enrollment or prove that a study had adequate power. They are planning illustrations, not observed power. The registry does not report a trial-specific sample-size justification, and the primary endpoint was not reduced to one comparison for this calculation.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, dose groups, time points, or statistical comparisons are examined. In general, testing many hypotheses can increase the chance of at least one apparently notable result under a null model. Researchers may address this with a prespecified hierarchy, an adjustment procedure, or a distinction between confirmatory and exploratory analyses. Which approach is appropriate depends on the design and aims.

The registry lists 63 outcome measures, but 0 analyses. It does not report a multiplicity strategy, a hierarchy among outcomes, or adjustments for multiple comparisons. The primary vital-sign endpoint itself covers several measures and categorical criteria, and the registry notes that it was not reduced to one comparison. The analysis plan, including any planned handling of multiple outcomes or time points, is not reported in the registry record.

The endpoint description specifies a population of treated healthy participants with safety parameters in the single-ascending-dose period, and explicitly excludes multiple-ascending-dose and psoriasis-cohort data. It does not state how missing vital-sign measurements were handled, whether participants with incomplete data were excluded, or whether any imputation was planned. Those missing-data procedures are not reported in the registry record.

In general, missing-data methods matter because the reason data are unavailable can affect how representative the analyzed participants are. A complete-case analysis, an imputation approach, and other strategies rely on different assumptions. Without a reported method or information about the amount and pattern of missingness, the impact on the primary endpoint cannot be assessed from the registry record.

The record also does not give a statistical analysis plan or a trial-specific sample-size justification. It therefore does not establish how the number of participants was chosen for the primary endpoint or how precision was expected to vary across dose cohorts.

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 lists serious adverse events, other adverse events, and deaths by group. The numbers below are participants at risk followed by participants with the event. Serious adverse events and deaths are recorded as 0 in every listed group. The other adverse-event counts are: Placebo SAD, 13 at risk and 1 affected; Placebo QD MAD (JP Placebo Included), 9 and 2; Placebo BID, 2 and 0; PF-06826647 3 mg SAD, 6 and 0; PF-06826647 10 mg SAD, 6 and 0; PF-06826647 30 mg SAD, 8 and 0; PF-06826647 30 mg QD MAD, 6 and 2; PF-06826647 100 mg SAD, 7 and 1; PF-06826647 100 mg QD MAD, 6 and 1; PF-06826647 400 mg SAD, 8 and 0; PF-06826647 400 mg QD MAD, 6 and 1; PF-06826647 1600 mg SAD, 6 and 2; PF-06826647 1200 mg QD MAD, 5 and 1; PF-06826647 200 mg BID, 7 and 3; PF-06826647 400 mg QD MAD JP, 5 and 1; Placebo QD PSO, 14 and 7; PF-06826647 400 mg QD PSO, 15 and 12; and PF-06826647 100 mg QD PSO, 11 and 5.

These are descriptive counts. In general, counts from groups with different sizes should not be compared as if they represented the same exposure or risk. The registry does not provide event definitions, event-level detail, follow-up duration for these listings, or statistical comparisons. Zero recorded serious events in these groups does not establish that serious events are impossible or that risks are equivalent between groups.

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

The registry record supports a description of the study's design and intended primary safety measure. It was a randomized phase 1 dose-escalation study of PF-06826647 in healthy subjects and subjects with plaque psoriasis, with placebo control. The primary endpoint concerned the number of healthy participants in the single-ascending-dose period who met prespecified vital-sign criteria from baseline up to Day 8.

The record does not report the primary endpoint counts, criterion thresholds, or an inferential analysis. Consequently, it does not quantify how often the criteria were met, estimate a difference between treatments, or show the precision of such a difference. The listed adverse-event counts provide separate descriptive safety information, but they cannot fill in missing primary endpoint results.

The listed pharmacokinetic outcomes indicate that the study was designed to characterize drug exposure, and the study description also identifies pharmacodynamic evaluation as an aim. Numerical outcome findings for those measures are not reported in the registry record. A stated study aim is not itself evidence of a result.

In general, a phase 1 dose-escalation study can provide early descriptive information about safety and exposure across cohorts. Its design and the registry data do not, by themselves, establish clinical efficacy, long-term safety, or the result that would be expected in a different population. The primary endpoint population is specifically restricted to healthy participants in the single-ascending-dose period, so it should not be treated as a psoriasis outcome.

The appropriate reading is therefore limited: the record identifies what was measured and lists adverse-event counts, but it does not supply the numerical primary outcome or analysis needed to quantify that endpoint.

13. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a broad study program and a narrowly defined primary endpoint population. The study included healthy subjects and subjects with plaque psoriasis and listed both single- and multiple-dose escalation. Yet the primary vital-sign endpoint applied only to healthy participants in the single-ascending-dose period. Keeping the target population clear is essential when interpreting any endpoint-specific result.

The endpoint also illustrates the difference between a continuous measurement and a categorical safety count. Blood pressure and pulse are measured values, while the primary outcome reduces them to whether prespecified criteria were met. In general, categorization can help communicate threshold events, but the thresholds and participant counts are necessary to interpret the result. Those elements are not reported in the registry record.

The record lists 63 outcome measures but 0 analyses. This makes a distinction between registered outcomes and available statistical results particularly important. An outcome's presence in a registry does not mean its results or inferential analysis are posted. The registry identifies pharmacokinetic measures and other study aims, but the numerical estimates needed to assess them are not reported in the registry record.

Finally, the adverse-event listings demonstrate why counts need context. Groups have different numbers at risk, and the listed cohorts differ by dose, schedule, and population label. In general, comparing raw counts without accounting for group size, exposure, and design can mislead. The registry supplies descriptive safety counts but no statistical comparison. This makes careful separation of descriptive evidence from inferential claims central to reading this study.

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 primary endpoint is described without its categorical thresholds, so the meaning of meeting a criterion cannot be independently evaluated. Although the record names the vital-sign measures and states the timeframe as baseline up to Day 8, it does not report the participant counts by treatment. The principal endpoint's numerical findings and any comparison are therefore unavailable in the registry record.

The analysis population is restricted to healthy participants in the single-ascending-dose period. The record explicitly excludes multiple-ascending-dose and psoriasis-cohort data from this endpoint. Any interpretation of the endpoint must respect that restriction and should not be generalized to all enrolled participants or treated as an assessment of psoriasis outcomes.

The registry lists 63 outcome measures and 0 analyses. It does not report a statistical analysis plan, multiplicity procedures, missing-data methods, or a trial-specific sample-size justification. It also does not report how dose escalation decisions were made or the specific allocation and masking procedures. These omissions limit assessment of the planned inferential framework and the robustness of potential results.

The adverse-event listings do not include event-level descriptions or statistical comparisons. The record gives counts for serious events, other events, and deaths, but these summaries alone cannot describe timing, duration, severity within the other-event category, or group differences in risk. The record's completed status and enrollment do not resolve these missing outcome details.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A First in Human Study to Evaluate Safety, Tolerability, and Pharmacology of PF-06826647 in Healthy Subjects and Subjects With Plaque Psoriasis — NCT03210961.
• Registry record last updated 2020-03-31; status last verified 2020-03.
• Results first posted 2020-03-31.
• 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

NCT03210961 is a completed phase 1 randomized, quadruple-masked, placebo-controlled dose-escalation study of PF-06826647 in healthy subjects and subjects with plaque psoriasis. The registry lists enrollment of 109, with study dates from 2017-07-14 to primary completion on 2019-01-25.

The primary endpoint counted healthy participants in the single-ascending-dose period who met prespecified vital-sign criteria from baseline up to Day 8. The registry describes the endpoint population and measures but does not report its thresholds or numerical results. It lists 63 outcome measures and 0 analyses. Adverse-event counts are reported by group; serious adverse events and deaths are recorded as 0 in each listed group. Numerical pharmacokinetic outcome results are not reported in the registry record.