Study of AMG 133 Administered Subcutaneously in Healthy Japanese and Caucasian Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of AMG 133 Administered Subcutaneously in Healthy Japanese and Caucasian Participants (NCT05056246), a randomized phase 1 study. The primary outcome is Maximum Observed Plasma Concentration (Cmax) of Intact AMG 133.

2. Clinical Question

The study was a Phase I, open-label, randomized, parallel-arm investigation in healthy participants. Its focus was pharmacokinetics, safety, and tolerability after one dose. Concentration sampling extended from pre-dose on Day 1 through the listed post-dose time points, with the primary endpoint reflecting the highest observed plasma concentration during that schedule.

The posted figures allow a descriptive look at the concentration summaries within each listed dose and participant group. They do not establish whether differences between groups are statistically distinguishable, nor do they isolate ethnicity as a cause of any difference. Dose amounts, a prespecified ethnic-group comparison, and inferential results are not reported in the registry record.

3. Trial Design

This was a Phase I, randomized, open-label, parallel-arm, single-dose study of AMG 133 in healthy Japanese and Caucasian participants. The record lists 34 participants enrolled and identifies the study as completed. The study start date was 2021-09-10, and primary completion was 2022-04-08.

AMG 133 was given by subcutaneous injection on Day 1. The listed arms were Japanese participants receiving low, medium, or high dose, and Caucasian participants receiving medium or high dose. The dose quantities are not reported in the registry record. There was no placebo arm among the posted groups. Although the study is described as randomized, the randomization procedure and allocation details are not reported in the registry record.

Open-label means that masking was not used. This is relevant to how subjective outcomes might be interpreted, but the primary outcome is a laboratory-measured plasma concentration. Parallel-arm means participants were listed in separate dose and participant-group arms rather than being described as receiving a sequence of doses.

The primary objective was to evaluate pharmacokinetics following a single administration. Blood samples were collected pre-dose on Day 1 and at 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose. The primary outcome was maximum observed plasma concentration of intact AMG 133. The registry also lists treatment-emergent adverse events and positive anti-AMG 133 binding antibody results as secondary outcomes.

The record does not report the rationale for the selected enrollment, a sample-size justification, or details of interim analyses. The listed planning assumptions describe illustrations based on an observed effect; they are not a description of the trial’s original design rationale or evidence of observed power.

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 34 participants were enrolled and randomized in the study. All 34 participants were dosed in accordance with the protocol.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) Population: Included all participants who received at least 1 dose of AMG 133 and had evaluable PK data.

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: Safety Population: Included all participants who received at least 1 dose of AMG 133.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Observed Plasma Concentration (Cmax) of Intact AMG 133, measured over Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose.

The primary endpoint is the maximum observed plasma concentration, or Cmax, of intact AMG 133. It is measured in μg/mL and summarizes the highest concentration recorded in a participant’s sampled plasma after administration. The registry reports arm-level geometric means and geometric coefficients of variation, rather than arithmetic means or confidence intervals.

Pharmacokinetic measures describe how a drug’s concentration changes in the body over time. Cmax is used to characterize peak exposure. It is distinct from the time at which the peak occurs and from measures that summarize exposure over the full sampling period. The registry record identifies concentration sampling from pre-dose on Day 1 through 2856 hours post-dose; it does not report a separate result for the time to peak concentration in the primary outcome.

General statistical context: concentration data can be right-skewed, with some observations substantially higher than others. A geometric mean is calculated on a logarithmic scale and then expressed on the original scale; it is often used to describe positive, skewed measurements. It should not be read as the ordinary arithmetic average. The geometric coefficient of variation describes relative spread on a multiplicative scale. It is a measure of variability, not a confidence interval or a range containing a stated proportion of participants.

The endpoint is a pharmacokinetic measurement, not a direct measure of clinical benefit. The posted summary does not provide individual concentration profiles, confidence intervals, or formal comparisons between arms.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is reported as a geometric mean with a geometric coefficient of variation. The arm-level summaries are useful for describing the observed concentration measurements, but they do not by themselves provide an inferential comparison between arms. No formal analyses are posted in the registry record.

Why use a geometric mean?

General statistical context: many biological concentrations are positive and can vary multiplicatively. In such settings, a value twice as large as another may be more meaningful than an equal absolute increase across the measurement scale. Taking logarithms converts multiplicative variation into additive variation for analysis. A geometric mean is obtained by averaging on the log scale and transforming back. It is consequently different from the arithmetic mean, which gives more influence to high values when a distribution is right-skewed.

A geometric mean should be read as a central summary on a multiplicative scale. It does not show the full distribution, and it does not imply that individual participants had concentrations near that value. The posted record provides no individual-level concentrations or quantiles to show the distribution directly.

What does the geometric coefficient of variation describe?

General statistical context: a coefficient of variation expresses variability relative to a central value. Its geometric form is suited to data analyzed on a log scale and describes multiplicative spread. It is not a confidence interval, a standard error, or a statement that a given percentage of observations fall within a particular interval. Larger values indicate more relative variability in the measurements under this summary, but do not tell whether an arm-level mean is estimated precisely.

The reported GCVs vary across the five arms. That variation is descriptive and should not be used alone to rank reliability or to infer differences in exposure. Precision of an estimated mean is usually conveyed with an uncertainty interval, and such intervals are not reported for the primary outcome in the registry record.

How should Cmax be understood?

Cmax is the largest observed plasma concentration during the specified sampling period. It is a standard pharmacokinetic summary of peak concentration. It is not the same as total exposure over time, which would require an exposure measure such as area under a concentration-time curve, and it does not identify when the peak occurred. The registry describes measurements of intact and total AMG 133, but the primary outcome is for intact AMG 133.

Because samples were taken at scheduled times, the maximum observed value depends on the sampling schedule as well as the concentration profile. A true peak between two scheduled samples could differ from the largest sampled value. The record does not report modeling of concentrations between visits or the method used to derive the maximum if a value was missing.

What can the arm summaries establish?

Arm-specific geometric means describe the posted data for the participants contributing to each arm’s PK outcome. They do not constitute a treatment contrast. A formal contrast would need a defined estimand, an analysis method, and an uncertainty estimate. The registry record does not report these for comparisons among doses or participant groups. Randomization is listed as a design feature, but the details of assignment and the comparison strategy are not reported.

General statistical context: a confidence interval gives a range of values compatible with the data and a specified analysis procedure, reflecting sampling uncertainty. It is not a range that guarantees the true value lies within it. Confidence intervals would help readers judge how precisely each arm summary is estimated and how uncertain the differences between arm summaries may be. No confidence intervals for the primary outcome are reported in the registry record.

How should planning illustrations be read?

The registry’s planning assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not the trial’s reported design justification. Any resulting sample-size figure is a planning illustration, not observed power and not evidence that the study had a particular probability of detecting an effect. No sample-size justification or rationale is reported in the registry record.

Those assumptions refer to a two-arm planning comparison, whereas the study lists multiple arms and no single control group. They should not be mistaken for a complete analysis plan for all dose and participant-group comparisons. The registry record does not report multiplicity adjustments, a prespecified hierarchy of comparisons, or the statistical procedure used for any formal hypothesis tests.

Finally, interpretation is constrained by the small arm-level counts, the absence of confidence intervals and inferential comparisons, and the lack of individual concentration data. These limitations do not invalidate the descriptive summaries, but they limit how far the summaries can be generalized or compared.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including the primary pharmacokinetic outcome and secondary outcomes for treatment-emergent adverse events and positive anti-AMG 133 binding antibody results. It reports 2 secondary outcomes, but the available record does not provide results for every listed measure in the registry record for this analysis. The analysis plan for multiple outcomes or multiple arm comparisons is not reported in the registry record.

Multiplicity arises when several outcomes or comparisons are examined: the chance of at least one apparently notable result can increase if many tests are conducted without an appropriate plan. General statistical context: researchers may address this by prespecifying a primary comparison, applying an adjustment, or interpreting results as exploratory. Which approach was used in this study is not reported in the registry record. No formal analysis results are posted.

The primary PK population is defined as participants who received at least 1 dose of AMG 133 and had evaluable PK data. Arm-level PK counts are reported alongside the geometric means. The registry record does not report how many randomized participants lacked evaluable PK data, how missing concentration measurements were handled, or whether any sensitivity analyses were performed.

The record reports enrollment of 34 participants, but it does not describe the flow from enrollment through dosing and analysis in sufficient detail to determine reasons for any exclusions or missing outcomes. An intention-to-treat population, per-protocol population, and rules for handling protocol deviations are not reported in the registry record. These omissions limit assessment of the potential effect of missing data on the posted summaries.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: road traffic accident (14.3%), cervical spinal stenosis (14.3%).

The registry reports serious adverse event counts by arm. Japanese participants in the low-dose and medium-dose arms had 0 serious events reported; the Japanese high-dose arm had 1. The Caucasian medium-dose and high-dose arms each had 0 serious events reported. Deaths were 0 in every listed arm. These are counts, not evidence that an event was or was not caused by AMG 133.

For other adverse events, the posted counts were 6 of 6.0 in the Japanese low-dose arm, 6 of 7.0 in the Japanese medium-dose arm, and 7 of 7.0 in the Japanese high-dose arm. In the Caucasian medium-dose and high-dose arms, the counts were 7 of 7.0 in each arm. These registry figures describe participants with reported events; they do not identify event severity beyond the separate serious-event classification.

The serious-event terms listed are Road traffic accident and Cervical spinal stenosis, each reported as 14.3%. The registry record does not provide enough context to attribute either term to a particular arm or to determine the denominator used for these percentages. Serious adverse event reporting is not, on its own, a causal assessment. The record’s adverse-event counts should be interpreted descriptively, especially given the small number of participants in each arm.

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

The primary results provide a pharmacokinetic description of maximum observed plasma concentration after a single subcutaneous dose of AMG 133 in the listed healthy-participant groups. They show the geometric mean and geometric coefficient of variation for each arm, with group-specific counts. This is useful information about the concentration summaries recorded during the study’s sampling schedule.

The results do not establish a treatment benefit. The study enrolled healthy participants and the primary outcome is a laboratory concentration measure, not a clinical outcome. No placebo arm is listed, and the registry record does not report a formal inferential comparison among dose arms or between Japanese and Caucasian participants. The descriptive arm values cannot establish that a difference is statistically significant, clinically important, or caused by participant group.

The study is Phase I and single-dose, so the record addresses pharmacokinetics and short-term safety observations in the described setting. It does not establish long-term safety, outcomes with repeated dosing, or effects in a patient population. The registry record does not report dose amounts, detailed participant characteristics beyond the stated groups, or an analysis of how individual characteristics relate to concentration.

Precision is also limited by the arm counts and the absence of confidence intervals and individual-level data. The GCVs describe relative variability, but they do not quantify uncertainty around the geometric means. Without formal comparisons and their uncertainty estimates, the posted values should be treated as descriptive rather than definitive evidence of differences.

Accordingly, the record supports a narrow conclusion: it documents reported Cmax summaries and adverse-event counts for the listed arms after a single administration. It does not, by itself, answer whether the pharmacokinetic profiles are equivalent across groups, whether any observed difference is meaningful, or whether the findings apply beyond the population and dosing conditions studied.

13. Why This Trial Matters Statistically

This study illustrates how early-phase pharmacokinetic work can be summarized without a conventional placebo-controlled efficacy comparison. Its primary result is a concentration measure, reported separately for dose and participant-group arms. That distinction matters: an arm-level geometric mean describes exposure in the observed data but is not a treatment-effect estimate against an untreated group.

Reporting geometric means and geometric coefficients of variation is consistent with the use of multiplicative summaries for concentration data. Readers still need uncertainty intervals and clearly specified contrasts to judge how precisely the estimates are known and how the groups compare. Those inferential details are not reported in the registry record. The posted summaries therefore support descriptive interpretation, while leaving the uncertainty around cross-arm differences unresolved.

The study also demonstrates why the design structure matters when reading results. Japanese and Caucasian participants appear in medium- and high-dose arms, but the low-dose arm is listed only for Japanese participants. The groups are small, and no formal ethnic-group analysis is reported. A visual or numerical contrast between arm summaries should not be mistaken for a controlled test of a group effect.

Safety counts are similarly informative but limited. Reporting serious events, other events, and deaths by arm makes the observed counts visible. With small groups, however, the counts provide limited information about the frequency of uncommon events or about causal attribution. The registry record does not provide enough detail to establish whether the listed serious-event terms were related to study treatment.

Finally, planning calculations based on an observed effect are not a substitute for a prospective sample-size rationale and cannot be read as observed power. Distinguishing descriptive summaries, inferential analyses, and planning illustrations is essential for interpreting early-phase trial results carefully.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation is that the registry reports arm-level Cmax summaries without confidence intervals, individual concentration data, or formal between-arm comparisons. The GCVs describe relative spread, not precision of the geometric means. As a result, the statistical uncertainty around each estimate and the contrasts between groups cannot be assessed from the posted results.

Each listed PK arm has a small count, ranging from 6.0 to 7.0. Estimates from small groups may be sensitive to individual observations, and the record does not provide distributions or participant-level profiles that would help assess this. The study includes medium- and high-dose arms for both participant groups, but the low-dose group is listed only for Japanese participants. Dose amounts are not reported, and no planned comparison by dose or participant group is specified.

The endpoint is the maximum concentration among sampled time points, so it may not coincide with the actual peak between samples. Although the schedule is reported, the registry does not provide individual sampling completeness or a method for handling missing concentration measurements. The PK population definition requires evaluable data, but the number and characteristics of any participants excluded from that population are not reported in the registry record.

The study was open-label and single-dose in healthy participants. The results do not address repeated dosing or a patient population. The record also does not report the randomization procedure, sample-size rationale, multiplicity strategy, or detailed analysis plan. Adverse-event counts are descriptive, and the serious-event terms are not linked to specific arms in the available record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of AMG 133 Administered Subcutaneously in Healthy Japanese and Caucasian Participants — NCT05056246.
• Registry record last updated 2025-02-25; status last verified 2025-01.
• Results first posted 2025-02-25.
• 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

NCT05056246 is a completed Phase I, randomized, open-label, parallel-arm, single-dose study of subcutaneous AMG 133 in healthy Japanese and Caucasian participants. The record lists 34 participants enrolled. Its primary objective was pharmacokinetic evaluation; the posted primary endpoint is maximum observed plasma concentration of intact AMG 133, summarized by arm as a geometric mean and geometric coefficient of variation.

The listed arms include low, medium, and high doses for Japanese participants and medium and high doses for Caucasian participants. Dose quantities are not reported in the registry record. The record also lists treatment-emergent adverse events and positive anti-AMG 133 binding antibody results as secondary outcomes. Serious-event and other adverse-event counts are reported by arm, with 0 deaths listed in each arm.

The posted PK results are descriptive. Formal comparisons, confidence intervals, missing-data details, and a sample-size justification are not reported in the registry record. The findings therefore characterize the recorded concentration summaries and safety counts without establishing inferential differences between arms.