Single-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 827: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Single-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 827 (NCT00867100), a randomized phase 1 study. The primary outcome is Part B: PASI (Psoriasis Area and Severity Index) Score Mean Percentage of Change Through Day 43.

2. Clinical Question

3. Trial Design

This was a Phase 1 randomized, double-blind, placebo-controlled, ascending single-dose study of AMG 827. Its official title describes a study in healthy subjects and subjects with moderate to severe psoriasis. The registry lists a parallel-group model and triple masking. The study summary states that AMG 827 was administered as a single SC or IV dose, with safety, tolerability, pharmacokinetics, and pharmacodynamics among the areas of evaluation.

The listed interventions include 140 mg SC, 350 mg SC, 700 mg IV, and placebo. The arm descriptions identify the active regimens as psoriasis cohorts. The posted PASI outcome is narrower than the overall study: it applies only to Part B subjects with moderate to severe plaque psoriasis. Its four groups are placebo, 140 mg SC, 350 mg SC, and 700 mg IV. The group sizes for this outcome are 5, 4, 8, and 8, respectively. These are the numbers attached to the outcome summaries, not the total study enrollment.

The registry reports overall enrollment of 84, a study start of 2007-12, primary completion in 2009-09, and completed status. It does not report how the ascending doses were assigned or sequenced beyond the listed design description. Further details about randomization procedures, allocation concealment, or the masking procedures are not reported in the registry record. The study’s planned sample-size justification is also not reported in the registry record.

The registry lists three outcome measures, but its posted results identify no secondary posted outcomes and no analyses. The Part B PASI summaries are therefore a descriptive view of one outcome, not a complete account of every safety, pharmacokinetic, or pharmacodynamic assessment named in the study objective. Details of those other assessments 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.

Only the first 6 of 13 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: This PASI outcome measure data refers only to Part B subjects with moderate to severe plaque psoriasis.

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 B: PASI (Psoriasis Area and Severity Index) Score Mean Percentage of Change Through Day 43, measured over Through day 43.

The posted primary endpoint is the mean percentage change in PASI score through day 43, for Part B participants with moderate to severe plaque psoriasis. The record describes the measure as percentage improvement and states that it summarizes change between baseline and day 43. PASI combines information about psoriasis area and severity; the registry describes its score range as (0), no disease, through (72), maximal disease.

A change expressed as a percentage offers a way to summarize how a participant’s score changed relative to baseline, while the group mean describes the average observed change among participants in that treatment group. It is not the same as reporting each participant’s score or the proportion who reached a specified response threshold. No such responder threshold is included in the posted endpoint description.

PASI is used in this study as a measure of psoriasis severity over time. That makes it relevant to the stated evaluation of pharmacodynamic effects in participants with psoriasis. However, the posted record gives only a group mean and standard deviation for each arm. It does not give a confidence interval, individual-participant data, or a formal comparison of the groups. The endpoint can therefore be read as a summary of the observed Part B changes through day 43, with uncertainty and comparative inference not fully described in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted PASI results are continuous-outcome summaries. For each Part B group, the registry reports a participant count, a mean percentage improvement, and a standard deviation. A mean is the arithmetic average of the observed values in a group. The standard deviation describes the spread of those values around the mean; it is not the standard error and it is not itself a confidence interval. Reading the mean and standard deviation together gives a more useful descriptive picture than reading the mean alone.

What does a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimate under a stated statistical method. For a treatment comparison, an interval would help show which differences remain reasonably compatible with the data and analysis assumptions. The registry does not post confidence intervals for the Part B PASI means or for differences between arms. It also does not post an inferential analysis for this endpoint. As a result, the displayed group summaries do not quantify comparative precision in that way.

Why are small group sizes relevant?

In general, estimates from smaller groups can be more sensitive to the values of individual participants. That matters because the PASI outcome groups contain 5, 4, 8, and 8 participants. A single unusual observation can have more influence on a group average when few observations contribute. The standard deviations show that observed variation differs across groups, but the registry does not supply participant-level values, distribution plots, or a description of how the analysis handled unusual observations.

How should the mean and spread be read?

The mean gives the average percentage change as summarized in the registry; the standard deviation indicates observed dispersion around that average. Neither statistic describes the percentage of participants who improved, and neither identifies the range of individual outcomes. The registry labels the endpoint as percentage improvement, but does not report a responder definition or a clinically meaningful threshold. Readers should therefore avoid treating a group mean as if every participant experienced that amount of improvement.

The standard deviation is also not a measure of uncertainty in the estimated mean. General statistical methods can use the sample size and variability to estimate uncertainty, but an interval or test depends on assumptions and a specified analysis. The registry record does not state such an analysis for the primary outcome. It would not be appropriate to present a newly calculated comparison as though it were the sponsor’s planned or reported analysis. The record indicates no discrepancy between posted results and any recalculation described for this page.

What do the planning illustrations mean?

Any sample-size illustrations accompanying this page are planning calculations based on the observed effect, not a record of the trial’s design justification and not observed power. The stated illustration assumptions are 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 fraction of the observed effect. In general, such an illustration asks how many participants per arm might be needed under those assumptions to detect a specified target difference. It does not show that the current trial had that power, nor does it establish that the assumptions match the original protocol. The trial’s own sample-size rationale is not reported in the registry record.

A planning estimate is particularly sensitive to the effect chosen for planning. An effect observed in a small study can be imprecise, and assuming that a future study will target that same magnitude is a planning choice rather than a guarantee. The illustrations are best read as conditional scenarios. They do not replace a protocol-based calculation, and they do not turn the posted descriptive results into a formal confirmatory finding.

What can be inferred without a posted comparison?

General statistical interpretation distinguishes description from inference. Description summarizes the observed participants; inference uses an analysis and assumptions to quantify what the data imply beyond them. The registry gives descriptive means and standard deviations for the Part B endpoint, but reports no analyses. It does not state a model, adjustment method, hypothesis test, or treatment-effect estimate with uncertainty for this outcome. Consequently, a visual separation of group means is not by itself a test of a treatment difference.

The registry record also does not say whether any planned interim analyses were conducted, how missing endpoint values were handled, or what analysis population was used beyond the statement that this PASI measure refers to Part B subjects with moderate to severe plaque psoriasis. Those details affect interpretation in general, but should not be inferred from the summary. The clearest reading is therefore to report the observed group summaries as posted, acknowledge their limited precision and small counts, and leave unreported analysis choices unresolved.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Placebo", "140 mg Sc", "350 mg Sc", "700 mg IV")
n   <- c(5, 4, 8, 8)
m   <- c(19.88, 17.74, 53.57, 86.04)
sp  <- c(6.36, 15.34, 30.45, 8.7)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Placebo  5  19.880  6.360  11.983  27.777
CARM  140 mg Sc  4  17.740  15.340  -6.669  42.149
CARM  350 mg Sc  8  53.570  30.450  28.113  79.027
CARM  700 mg IV  8  86.040  8.700  78.767  93.313

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures but posts no secondary outcome results and no analyses. It does not report a multiplicity strategy for the PASI endpoint or for other outcomes. In general, multiplicity matters when several outcomes, time points, or comparisons are tested: without a stated plan, readers cannot tell whether or how the chance of false-positive findings was controlled. Here, because no inferential tests are posted, there is no reported adjustment to evaluate. The registry’s lack of detail should not be mistaken for evidence that multiplicity was or was not addressed in the original study.

The outcome description refers to PASI change over time between baseline and day 43, while the posted measure is a mean percentage change through day 43. The registry does not state which observations contributed at intermediate times, whether a particular visit was selected for analysis, or how repeated measurements were modeled. The method used to handle missing PASI data is not reported in the registry record. It also does not say whether participants with incomplete follow-up were included in the summary, excluded, or handled through another method.

The population statement identifies Part B participants with moderate to severe plaque psoriasis, but further details of the analysis population are not reported in the registry record. In particular, the record does not describe an intention-to-treat population, a per-protocol population, or criteria for inclusion in the endpoint analysis. These omissions limit assessment of possible bias from missing observations or exclusions. They do not establish that such issues occurred; they mean the posted record does not explain how they were addressed.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event summaries list serious adverse events separately from other adverse events. For each listed group, the registry records zero participants with a serious adverse event. This includes the Part B groups as well as the listed Part A cohorts. The displayed serious-event counts therefore describe what was recorded in these groups; they do not by themselves establish the absence of risk beyond the observation captured in this study.

The other-adverse-event counts are broader. In Part B, the registry lists 5 affected participants among 5 in placebo, 4 among 4 in the 140 mg SC cohort, 8 among 8 in the 350 mg SC cohort, and 8 among 8 in the 700 mg IV cohort. In Part A, the counts vary by cohort; the registry lists 5 affected participants among 6 in Cohort 7: 420mg SC Part A, and all participants in the other listed Part A groups as affected. These counts should not be confused with serious adverse events.

Death counts are not reported in the registry record. The adverse-event table does not provide the event terms in the top serious-terms field. The registry’s figures are counts of affected participants, not a detailed account of event type, duration, severity, or relationship to treatment. They should be read as a limited descriptive safety summary, not as a complete safety assessment.

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

The results show the Part B PASI summaries observed through day 43 in small groups receiving placebo or one of three single-dose AMG 827 regimens. The reported group means differ, with the highest posted mean in the 700 mg IV group and a lower mean in the placebo and 140 mg SC groups. The summaries also show substantial variability in some groups. These features describe the data in this registry record; they do not establish a causal treatment effect or a statistically supported difference between regimens.

The record does not report confidence intervals, p-values, or an analysis model for the primary endpoint. It therefore does not show the precision of the group differences or whether a formal comparison met a statistical threshold. The group means should not be interpreted as predictions for an individual participant, nor do they establish how outcomes would look beyond the stated population and time window. The registry also does not provide longer-term PASI results in the posted material.

The study was Phase 1 and included evaluation of safety, tolerability, pharmacokinetics, and pharmacodynamics. The posted PASI outcome addresses a pharmacodynamic question in the Part B psoriasis group, not every study objective. The registry’s overall enrollment of 84 should not be confused with the much smaller group counts for this outcome. Nor should the Part B values be extended to healthy subjects or to the separate Part A cohorts.

In short, the posted results are useful as descriptive observations and as a basis for understanding what the study measured. Without the study’s full analysis plan, missing-data approach, comparative estimates, or uncertainty intervals in the registry record, stronger conclusions about the reliability or generalizability of between-group differences are not supported by these summaries alone.

14. Why This Trial Matters Statistically

This study illustrates why a trial’s overall enrollment and an endpoint’s analysis population should be read separately. Although the registry reports enrollment of 84, the primary PASI summaries concern only Part B participants with moderate to severe plaque psoriasis, and each arm contributes a small number of observations. The distinction matters when interpreting the apparent precision of an average: the total study enrollment does not determine the precision of a subgroup endpoint if other participants do not contribute to that outcome.

It also illustrates the difference between a descriptive pattern and a comparative result. The posted means and standard deviations allow readers to see how the groups’ observed summaries differ and how variable values were within groups. But the registry reports no analyses, confidence intervals, or p-values for the endpoint. A plot may make differences visually salient, yet visual separation is not a substitute for an analysis that states its assumptions and quantifies uncertainty.

The study also combines dose and route distinctions in the Part B regimens. The descriptive summaries are useful for seeing the observations associated with each listed regimen, but the registry does not report a dose-response analysis or a method that isolates dose from route. This is a reminder that interpreting a pattern across treatment groups depends on how the comparison was planned and analyzed, not simply on the order of the labels.

Finally, the posted planning illustrations should be kept distinct from the trial’s design. A calculation based on observed effects can help frame future sample-size planning, but it is not evidence of the study’s original justification or of observed power. These distinctions are important for biostatisticians and clinical researchers because they separate what the registry directly documents from what would require further protocol or analysis information.

15. 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 Part B PASI groups are small: the posted counts are 5 for placebo, 4 for 140 mg SC, and 8 each for 350 mg SC and 700 mg IV. Small groups make the summaries sensitive to the individual observations. The registry supplies group means and standard deviations, but not participant-level results or confidence intervals. Readers cannot use the posted summaries to assess the full shape of each group’s outcome distribution.

The endpoint is confined to Part B participants with moderate to severe plaque psoriasis and change through day 43. The record does not report results for longer follow-up or a separate analysis for healthy subjects. The Part B comparisons also span SC and IV regimens, and the registry does not report a statistical analysis separating route and dose effects. The outcome description does not provide a responder threshold or additional clinical interpretation of the percentage changes.

The registry record does not report the statistical analysis plan, the treatment contrast of primary interest, the handling of missing outcome data, or the analysis population definition beyond the Part B description. It also does not report multiplicity handling, interim analyses, or a sample-size justification. No inferential results are posted for the PASI outcome. These gaps prevent a full assessment of the planned analysis and the uncertainty around comparisons.

Safety reporting is also limited in this record. Serious adverse-event counts are shown, but deaths are not reported and the top serious-event terms are not listed. The counts for other adverse events do not provide event descriptions or detailed timing. These limitations are specific to what the registry record contains; they do not establish that additional analyses or information were absent elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Single-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 827 — NCT00867100.
• Registry record last updated 2019-01-16; status last verified 2018-07.
• Results first posted 2019-01-16.
• 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.

19. Record Summary

The registry record describes a completed Phase 1, randomized, triple-masked, parallel-group, placebo-controlled, ascending single-dose study of AMG 827 in healthy subjects and subjects with moderate to severe psoriasis. Overall enrollment was 84. The listed Part B regimens were 140 mg SC, 350 mg SC, 700 mg IV, and placebo.

The primary outcome is mean percentage change in PASI through day 43 among Part B participants with moderate to severe plaque psoriasis. The registry posts group means and standard deviations but no endpoint analyses, confidence intervals, or p-values. It lists three outcome measures, with no secondary results posted. Serious adverse-event counts are zero in each listed group; death counts are not reported in the registry record.

The record does not report the statistical plan, missing-data methods, analysis population details beyond the Part B description, or sample-size justification. The posted results therefore support a descriptive reading of the recorded summaries, while leaving important aspects of comparative inference unresolved.