Copper Balance in Healthy Participants Administered ALXN1840: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Copper Balance in Healthy Participants Administered ALXN1840 (NCT04594252), a na phase 1 study. The primary outcome is Change From Baseline in Mean Daily Copper Balance Over 2 Weeks of Repeated Daily ALXN1840 Dosing (Over Days 4 to 15).

2. Clinical Question

The study asked how mean daily copper balance changed from baseline during repeated ALXN1840 dosing in healthy participants. Its primary measure focused on Days 4 to 15 of dosing, and the registry defines copper balance as copper input minus copper output.

Input was defined as copper measured in food and fluids over the specified period. Output was copper measured in urine and feces over the specified collection period. A negative balance therefore represents greater measured output than intake; it does not, by itself, describe why that balance occurred.

The primary question is descriptive of change during treatment in this group. Without a separate control group, the study design does not provide a randomized comparison that can isolate a difference between ALXN1840 and another treatment or no treatment.

3. Trial Design

This was a Phase 1, open-label study with a single-group model and no masking. The registry record lists 17 enrolled participants and identifies the condition as healthy. The intervention was ALXN1840, administered as repeat doses of 30 milligrams (mg) for 15 days. The study status is completed; the recorded study start was 2020-07-01 and primary completion was 2020-11-18.

The design centered on measurement of copper balance during dosing rather than on comparison of randomized treatment groups. The registry explicitly describes allocation as not applicable and identifies the study as not a randomized comparison. There is no separate placebo or active-comparator arm in the listed design. The group labels in the safety record do not change the single-group design description, and the registry does not explain further how those labels relate to study procedures.

The primary outcome was change from baseline in mean daily copper balance over Days 4 to 15. The baseline definition used the average of nonmissing measurements on or before first study-drug administration from Day -4 to Day -1. The full analysis set was defined as participants who received at least 1 dose of ALXN1840. The record does not report how many participants met that definition or how many contributed data to the primary outcome.

The registry lists 12 outcome measures, including measures of copper and molybdenum balance, excretion, and concentrations over specified periods. These are listed outcomes, not numerical findings. No outcome analysis results are reported in the registry record. A detailed protocol, statistical analysis plan, and sample-size justification are not reported in the registry record, so the planned rationale for the design cannot be reconstructed from this information.

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 17 participants were enrolled in 2 groups. Group 1 consisted of 6 participants. Group 2, consisting of 11 participants, was initiated after the Safety Review Committee (SRC) reviewed safety information from Group 1. No safety concerns were identified; therefore, no dose adjustments were implemented with Group 2.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set included all participants who received at least 1 dose of ALXN1840.

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: Full analysis set included all participants who received at least 1 dose of ALXN1840.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Mean Daily Copper Balance Over 2 Weeks of Repeated Daily ALXN1840 Dosing (Over Days 4 to 15), measured over Baseline, Days 4 to 15.

The primary endpoint was change from baseline in mean daily copper balance over two weeks of repeated daily ALXN1840 dosing, specifically over Days 4 to 15. It was expressed in mg/day. The registry defines copper balance as the difference between copper input and copper output. Input was measured from food and fluids; output was measured in urine and feces.

Baseline was defined as the average of nonmissing values on or before the first administration of study drug from Day -4 to Day -1. The endpoint compares that baseline measure with the mean daily balance during the stated dosing window. The registry identifies the summary as a mean with standard deviation, but does not report the primary endpoint estimate or its standard deviation.

A balance measure combines intake and measured excretion into a single quantity. As a matter of general interpretation, a negative balance means measured output exceeds measured intake; a positive balance means measured intake exceeds measured output. This accounting measure is not itself an explanation of the biological processes behind the observed inputs or outputs.

Repeated measurements across a defined window can describe average balance during that period rather than a single day's value. That makes the endpoint relevant to the study's stated aim of assessing copper balance during repeated dosing. However, the registry record does not give the numerical change, its uncertainty, or participant-level observations. The direction and precision of the observed primary change therefore cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean describe?

The primary outcome is a mean, a summary of the measured daily copper balance during the specified period. In general, a mean gives a central value across observations, but it can conceal variation among individual observations. The registry identifies standard deviation as the measure of dispersion intended to accompany the mean. In general, standard deviation describes how spread out observations are around their mean; it is not the same as uncertainty in the estimated mean. Neither the primary mean nor its standard deviation is reported in the registry record.

What is a change from baseline?

The endpoint compares a baseline measure with measurements during Days 4 to 15. The registry defines baseline as the average of nonmissing measurements on or before the first study-drug administration from Day -4 to Day -1. A change-from-baseline summary expresses the difference between a later measurement or period average and baseline. As a general matter, the meaning of the sign depends on how the difference is defined. The registry names the outcome as a change from baseline but does not report its numeric value, so its direction cannot be interpreted.

What does copper balance represent?

The record defines balance as copper input minus copper output. Input was measured in food and fluids, and output was measured in urine and feces over the specified collection period. Thus a negative value indicates greater measured output than intake. This is a measurement-based accounting quantity. General interpretation should distinguish it from a direct explanation of the processes that led to intake, excretion, or any observed change.

How should uncertainty be assessed?

In general, a confidence interval describes a range of values compatible with the data and a stated statistical procedure; narrower intervals indicate greater precision under that procedure. A p-value, when reported, addresses compatibility between data and a specified null hypothesis under model assumptions. Neither statistic can be interpreted without knowing the estimate, analysis, and assumptions. The registry record does not report a confidence interval, p-value, or detailed inferential method for the primary outcome. It is therefore not possible to characterize statistical uncertainty or statistical significance from the record.

What does the design permit?

This is a single-group, open-label study, not a randomized comparison. In general, a within-group baseline comparison can describe how measurements differ over time, but a change does not alone establish that the intervention caused it. Without a separate control group, other time-related influences cannot be distinguished by a randomized contrast. Open-label status means masking was not used, but the record does not state whether this affected measurement or conduct.

What about sample-size planning?

The registry's planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such a planning illustration is not the study's design: the recorded trial is single-group and has no randomized comparison. Planning values are hypothetical quantities for considering a future comparison, not observed power for this trial. The underlying numerical effect and the resulting planning values are not reported in the registry record. A protocol-based sample-size justification is also not reported in the registry record.

What analysis details are unavailable?

The registry record does not report a statistical analysis plan, details of the model used for the primary endpoint, handling of repeated measurements, or methods for missing outcome data. The full analysis set is defined as participants who received at least 1 dose, but the record does not report the number contributing primary outcome data or whether the analysis set was applied as defined. These omissions prevent a more detailed assessment of how the endpoint was estimated.

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("Group 1: ALXN1840", "Group 2: ALXN1840")
n   <- c(6, 11)
m   <- c(-0.0749, 0.6901)
sp  <- c(0.37419, 0.48176)
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  Group 1: ALXN1840  6  -0.075  0.374  -0.468  0.318
CARM  Group 2: ALXN1840  11  0.690  0.482  0.366  1.014

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures. These include copper balance and excretion measures, molybdenum balance and excretion measures, and plasma copper and labile bound copper concentrations. Having multiple outcomes raises a general statistical question: when many outcomes are assessed, the chance of at least one apparently unusual finding can increase if each is considered separately. Researchers may address this through a prespecified hierarchy, adjustment, or other strategy, but the registry record does not report a multiplicity plan. It is therefore not possible to tell whether adjustments were planned or how findings across outcomes were intended to be interpreted together.

Numerical analyses are not reported in the registry record. The record does not provide primary or secondary outcome estimates, uncertainty intervals, or p-values. It also does not report a statistical analysis plan describing which analyses were prespecified, how model assumptions were to be assessed, or what sensitivity analyses were intended. The absence of those details should not be filled in by assuming common practice.

The primary measure's baseline definition uses nonmissing values from Day -4 to Day -1, and the full analysis set includes all participants who received at least 1 dose. However, the registry record does not report the number with available baseline and follow-up measurements, the number included in the primary analysis, or how missing values were handled. It does not say whether participants with incomplete measurement periods were excluded, whether any imputation was used, or how missing data affected secondary outcomes. Those details are important because missing observations can affect the estimate and its precision.

The record's planning assumptions describe a two-arm illustration, whereas the trial design is single-group. This illustration is a planning aid, not evidence of a randomized comparison or an estimate of this trial's power. Sample-size justification and a fuller account of the analysis populations are not reported in the registry record.

12. 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 safety record presents Group 1, Group 2, and a total row. For serious adverse events, the at-risk and affected counts are 6 and 0 in Group 1, 11 and 0 in Group 2, and 17 and 0 in the total row. The recorded death counts are 0 for each group and 0 in the total row. No serious adverse event terms are listed.

For other adverse events, the at-risk and affected counts are 6 and 5 in Group 1, 11 and 9 in Group 2, and 17 and 14 in the total row. These are counts, not rates, and no percentages should be inferred from them. The total row is a registry summary; the individual group labels are retained as recorded and do not establish separate randomized treatment arms.

In general, a count of affected participants does not describe the number, type, duration, severity, or timing of events. Nor does it establish whether an event was caused by treatment. The registry record does not provide those details in the safety information. The absence of listed serious events in these counts should be read as a description of the recorded safety summary, not as proof that no safety concern is possible.

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

This study addresses a measurement question in healthy participants: how mean daily copper balance changed from baseline during repeat dosing with ALXN1840. The registry defines the endpoint, the measurement components, and the periods used for baseline and treatment. It also identifies a single-group, open-label Phase 1 design and lists several additional copper and molybdenum outcomes.

The central limitation for interpreting the finding is that the numerical primary outcome is not reported in the registry record. Without the estimated change and a measure of its uncertainty, the direction, magnitude, and precision of the observed result cannot be evaluated. The endpoint description is not a substitute for an outcome estimate. Likewise, listed secondary outcomes cannot be treated as results when their numerical analyses are not reported.

Even if a within-group change were available, the design would describe measurements over time in the treated group rather than provide a randomized comparison with a control group. General statistical reasoning cautions that an observed before-and-during difference alone cannot isolate the effect of treatment from all other possible influences over time. The registry does not report additional design or analysis details that would change that distinction.

The safety counts report zero serious adverse events and zero deaths in the listed groups, alongside counts of participants affected by other adverse events. Those summaries are limited: the registry record does not list serious event terms and does not provide details sufficient to characterize all events or their relationship to treatment.

Accordingly, the record supports a description of the research question and the planned measurement framework, but not a conclusion about the numerical copper-balance change. It also does not establish comparative effects, explain biological mechanisms, or provide a comprehensive assessment of safety. Those conclusions require information not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable for its focus on a quantitative balance measure rather than a conventional between-group treatment contrast. Copper balance combines measured input from food and fluids with measured output in urine and feces. The endpoint therefore depends on defined collection periods and on how those inputs and outputs are summarized. Clear operational definitions are essential for readers to understand what a balance value represents.

The baseline and treatment windows are also central to the estimand: baseline uses nonmissing values on or before first administration from Day -4 to Day -1, while the primary measure concerns Days 4 to 15. Those definitions clarify the intended comparison over time. At the same time, the numerical estimate and its variability are not reported in the registry record, so readers cannot assess the observed change or its precision.

The single-group design makes the distinction between description and causal comparison especially important. A mean change from baseline, if reported, would characterize measurements in participants receiving ALXN1840; it would not be a randomized contrast with an untreated or alternative-treatment group. This distinction is broadly useful when interpreting early-phase research and physiological measurement studies.

The registry also lists 12 outcome measures and does not report a multiplicity strategy, missing-data methods, or detailed analysis plan. These omissions illustrate why outcome definitions alone do not fully specify statistical interpretation. Analysis populations, missing observations, uncertainty, and the handling of multiple outcomes all shape how results should be read.

Finally, planning illustrations based on an observed effect should not be confused with the trial's design or with observed power. The record describes a single-group study, while the stated planning assumptions use equal allocation between two arms. The contrast between those descriptions reinforces the need to distinguish hypothetical future-study planning from analyses of the trial itself.

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 most direct limitation of the registry information is that it does not report the numerical primary endpoint result. The mean change from baseline, its standard deviation, and any confidence interval or p-value are not reported in the registry record. Consequently, neither the direction nor the precision of the primary finding can be evaluated.

The study was open-label and single-group, with no randomized comparator. A within-group change would not provide a like-for-like control comparison. This restricts causal interpretation, even if numerical outcome findings were available. The registry does not report additional design features that would resolve this limitation.

The record lists 12 outcome measures but does not describe how multiplicity was handled. It also does not report the statistical analysis plan, the primary analysis method, or any sensitivity analyses. The full analysis set is defined by receipt of at least 1 dose, but the number of participants included in the primary analysis is not reported in the registry record.

Missing-data handling is not reported. The record does not specify the completeness of copper input and output measurements, how incomplete collection periods were treated, or whether missing values were imputed. Such information is relevant for a balance outcome built from measurements across intake and excretion sources.

Although the safety summary includes counts for serious and other adverse events, it does not provide event terms for serious events, event timing, severity, or causal attribution. Further, the meaning of the two group labels in the safety record is not explained. Finally, a protocol-based sample-size justification is not reported in the registry record. These limitations restrict evaluation of both the outcome analysis and the completeness of the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Copper Balance in Healthy Participants Administered ALXN1840 — NCT04594252.
• Registry record last updated 2024-08-19; status last verified 2024-03.
• Results first posted 2024-08-19.
• 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

NCT04594252 is a completed Phase 1, open-label, single-group study titled “Copper Balance in Healthy Participants Administered ALXN1840.” The registry lists 17 enrolled participants and an intervention of repeat ALXN1840 doses of 30 milligrams (mg) for 15 days. The recorded study start was 2020-07-01, and primary completion was 2020-11-18.

The primary endpoint was change from baseline in mean daily copper balance over Days 4 to 15. Balance was defined as copper input minus output, with input measured in food and fluids and output in urine and feces. The registry record does not report a numerical primary outcome result or a detailed statistical analysis plan.

The safety record lists 0 serious adverse events and 0 deaths in the total row, alongside 14 participants affected by other adverse events. These counts do not provide event-level detail. Overall, the registry describes the study question and its measurement framework but does not report the numerical primary finding or its statistical precision.