A Study to Evaluate the Safety of MEDI2338 in Subjects With Chronic Obstructive Pulmonary Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety of MEDI2338 in Subjects With Chronic Obstructive Pulmonary Disease (NCT01322594), a randomized phase 1 study. The primary outcome is Incidence of Adverse Events.

2. Clinical Question

3. Trial Design

This was a Phase 1 study of single ascending doses of MEDI2338 in participants with COPD. The registry lists randomized allocation and single masking, and identifies the study model as single-group. These labels do not fully explain how randomization and masking operated across the dose cohorts; further details are not reported in the registry record. The record describes five MEDI2338 dose groups and a placebo group, each receiving a single fixed intravenous infusion.

The dose groups were MEDI2338 10 MG, 30 MG, 100 MG, 300 MG and 1000 MG, alongside placebo. The infusion was administered over a minimum of 60 minutes using an infusion pump. The study summary describes the enrolled population as having stable, mild to moderate COPD. Enrollment was 31. The registry states that all 31 participants entered into the study received MEDI2338 or placebo and were included in the primary analysis.

The study status is completed. The registry lists a start of 2011-03 and primary completion of 2011-11. The primary endpoint was incidence of adverse events, counted as participants experiencing an event during Days 1 - 92. Secondary outcomes include serum concentration measures, anti-drug antibodies, maximum concentration, terminal elimination half-life and clearance. Their numerical results are not part of the posted primary endpoint results.

The registry does not report details about sequence generation, allocation concealment, cohort assignment, dose-escalation rules, or the specific masking procedures. It also does not describe the rationale for the chosen enrollment or provide a protocol-based sample-size justification. Consequently, the design can be characterized using its recorded labels and intervention descriptions, but not reconstructed beyond those details.

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: Eligibile participants in the 10 and 30 mg dose groups received MEDI2338 in an open-label manner. Eligible participants in the 100, 300, and 1000 dose groups were randomized in a 3:1 ratio to receive MEDI2338 or placebo.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All 31 participants entered into the study received MEDI2338 or placebo and were included in the analysis

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 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Adverse Events, measured over Days 1 - 92.

The primary endpoint is the incidence of adverse events, measured as the number of participants experiencing an event. The registry defines this endpoint to include both adverse events and serious adverse events. Its stated observation timeframe is Days 1 - 92. This is a participant count, not a count of all individual event episodes: the endpoint records whether participants experienced adverse events during the specified period.

Safety and tolerability are the stated focus of this Phase 1 study. Counting participants with events provides a direct descriptive summary of how many participants in each dose group and placebo group had an adverse event recorded. It is useful for presenting early safety observations across the tested doses, while the separate serious-adverse-event information distinguishes events classified as serious from other adverse events.

The posted results give a count and group size for each listed arm. MEDI2338 10 MG had 3 participants with adverse events among 3 participants; MEDI2338 30 MG had 3 among 3; MEDI2338 100 MG had 6 among 6; and MEDI2338 300 MG had 7 among 7. MEDI2338 1000 MG had 5 among 6, while placebo had 6 among 6. These are descriptive counts. The registry does not post a statistical comparison, uncertainty interval, or adjusted estimate for the primary endpoint.

The endpoint does not by itself identify event type, severity among non-serious events, timing within the follow-up period, or whether an event was caused by treatment. Those details are not reported in the primary endpoint results in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either experienced an adverse event during the stated timeframe or did not, according to the endpoint definition. The registry reports the number of participants with events and the group size for each arm. Such counts are a transparent way to describe an outcome, but they do not alone quantify the uncertainty around the underlying event probability or establish a difference between groups.

What do the counts describe?

Each arm-specific count describes participants with at least one adverse event, rather than the total number of adverse-event episodes. For example, the 1000 MG group has 5 participants recorded with an event among 6 in that group. The primary endpoint combines adverse events and serious adverse events, so the primary count does not distinguish seriousness. Serious-event counts are separately reported as 0 for every group.

A group size is essential context for interpreting a count. The same count can represent different proportions when group sizes differ. No new percentages or comparative estimates are needed to read the posted results, and the registry does not report formal estimates of relative or absolute differences. The posted counts should therefore remain descriptive rather than being treated as an effect estimate.

Why does uncertainty matter?

In general, a confidence interval describes a range of values compatible with the data under a specified statistical method. It communicates uncertainty as well as the estimated effect. With small groups, estimates of event frequency can be imprecise, and a change in one participant's outcome can materially affect the group summary. Confidence intervals for this endpoint are not reported in the registry record.

In general, a statistical test evaluates how compatible observed data are with a stated null hypothesis under its assumptions. A p-value is not a measure of clinical importance, nor does it show the probability that a treatment is effective. The registry reports no p-value or test result for the binary primary endpoint. The recorded skip reason indicates that values are missing or not estimable for a two-arm comparison of this binary endpoint. Accordingly, there is no posted two-arm comparison to interpret.

What role does the study design play?

Randomization, when its procedures are adequately described and carried out, can help balance factors between groups. Masking can reduce some forms of influence on treatment delivery or outcome assessment. Here, the registry labels the allocation randomized and masking single, but it does not report the operational details needed to assess those procedures. Its single-group model label also makes the design description incomplete for understanding the listed dose and placebo arms. These limitations do not change the counts, but they restrict what can be inferred from comparisons between arms.

In general, a dose-ranging safety study can present outcomes across dose groups to describe observed patterns. Such patterns do not, without a suitable analysis and adequate precision, establish a dose-response relationship. The counts in this record do not form a monotonic increase across the listed groups: the endpoint count is the same as the group size in several arms, while one participant in the highest listed dose group had no recorded adverse event. That is a description of the counts, not evidence about the cause of events or a trend in risk.

What is reported about analysis?

The registry states that all 31 participants entered into the study received MEDI2338 or placebo and were included in the primary analysis. The number of posted analyses is 0. No model, test, confidence-interval method, covariate adjustment, or missing-data method is reported in the registry record. No sponsor comparative analysis is posted for the primary endpoint.

The registry also describes a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the target effect is a fraction of the observed effect, and distinguishes participant-per-arm outputs from total-event outputs for time-to-event outcomes. Such illustrations are planning exercises, not observed power and not evidence that the original trial was designed using those assumptions. The registry does not report the trial's own sample-size justification.

In general, over-dispersion matters when outcomes vary more than a statistical model assumes, because standard errors can then be too small and uncertainty understated. This endpoint is a participant-level binary outcome, and no model or dispersion estimate is reported. There is no basis to infer an over-dispersion adjustment or other analytic procedure from the posted counts.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("MEDI2338 10 MG", "MEDI2338 30 MG", "MEDI2338 100 MG", "MEDI2338 300 MG", "MEDI2338 1000 MG", "Placebo")
n      <- c(3, 3, 6, 7, 6, 6)
events <- c(3, 3, 6, 7, 5, 6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  MEDI2338 10 MG  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  MEDI2338 30 MG  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  MEDI2338 100 MG  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  MEDI2338 300 MG  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7
ARM  MEDI2338 1000 MG  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3
ARM  Placebo  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six secondary outcome measures: area under the serum concentration-time curve from time zero to infinity; area under the serum concentration-time profile from time zero to the last measurable time point; incidence of anti-drug antibodies to MEDI2338; observed maximum concentration; apparent terminal elimination phase half-life; and clearance. These outcomes address pharmacokinetic and immunogenicity measures in addition to the primary safety endpoint.

When a study examines multiple outcomes, general statistical practice recognizes that repeated testing can increase the chance of a chance finding. A prespecified strategy may address this through a hierarchy, adjustment, or another approach. The statistical plan for multiplicity, including whether any adjustment was intended or applied, is not reported in the registry record. The registry lists no posted analyses, and the available primary results do not include inferential testing.

The primary analysis population is described as all 31 participants entered into the study, who received MEDI2338 or placebo and were included in the analysis. The registry does not provide a separate intention-to-treat, per-protocol, or safety-population definition beyond that statement. It also does not report participant-level missingness, exclusions, missing outcome handling, or sensitivity analyses. The listed arm counts and denominators are available for the primary endpoint, but further detail on incomplete observations is not reported in the registry record.

These omissions limit assessment of how the analyses were planned and how missing data or multiple outcomes may have influenced interpretation. They do not change the descriptive counts, but they prevent fuller evaluation of the statistical analysis plan.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious-adverse-event figures are participant counts. The registry reports 0 serious adverse events among 6 placebo participants, 0 among 3 participants in MEDI2338 10 MG, 0 among 3 in 30 MG, 0 among 6 in 100 MG, 0 among 7 in 300 MG, and 0 among 6 in 1000 MG. These are the serious-event counts recorded for the study groups.

The primary endpoint is broader: it includes participants with any adverse event, whether or not serious. Thus, the zero serious-event counts do not mean that no adverse events were recorded. The primary endpoint counts are 6 for placebo, 3 for 10 MG, 3 for 30 MG, 6 for 100 MG, 7 for 300 MG and 5 for 1000 MG. The registry's separate non-serious adverse-event counts show affected participants in each group, including every participant in each group except 1000 MG, where 5 of 6 were affected.

Death counts are not reported in the registry record. The absence of a reported serious event in these small groups should be read as an observation during the study, not proof that serious events are impossible or that risk is absent. The record does not report a comparative statistical analysis or causal assessment of the events.

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

The results describe adverse events recorded during Days 1 - 92 among participants assigned to the MEDI2338 dose groups or placebo. The endpoint counts indicate that adverse events were recorded for all participants in the 10 MG, 30 MG, 100 MG and 300 MG groups and all placebo participants; in the 1000 MG group, 5 of 6 participants had an event recorded. Serious adverse-event counts were 0 for every group.

These findings do not establish that MEDI2338 caused the recorded events. The primary endpoint includes all adverse events as well as serious adverse events, and the registry does not report event-by-event attribution, a causal assessment, or a comparative statistical analysis. The results also do not show whether any difference between groups is statistically distinguishable from random variation.

The study's small arm sizes constrain precision and generalizability. A handful of observations can change the descriptive pattern, and the registry reports no confidence intervals to quantify uncertainty. The observed counts should not be treated as precise estimates of what would occur in a broader COPD population or under other treatment conditions.

The registry characterizes this as a Phase 1 single ascending dose study. Its purpose, as recorded, was to evaluate safety and tolerability. The listed secondary outcomes include pharmacokinetic and anti-drug-antibody measures, but the posted primary endpoint results alone do not answer those other questions. Nor do the adverse-event counts provide evidence about long-term safety, repeated dosing, or outcomes outside the reported timeframe.

In statistical terms, the record supports a description of what was observed in the enrolled participants. It does not support a claim that treatment is beneficial, harmful, equivalent to placebo, or free of serious risk. The absence of a posted two-arm analysis and the limited group sizes are important boundaries on interpretation.

14. Why This Trial Matters Statistically

This study illustrates how early-phase safety results can be informative as descriptive observations while remaining limited for comparative inference. The registry reports participant counts for adverse events across five MEDI2338 dose groups and placebo, along with separate serious-adverse-event counts. This makes it possible to see what was recorded in each group without implying that a formal treatment effect was estimated.

The distinction between a count and an analysis matters. The primary outcome is a binary participant-level measure, but the record contains no posted two-arm statistical analysis, confidence interval, or p-value. With small group sizes, the counts are sensitive to individual outcomes. A comparison of raw counts alone would not account for uncertainty or establish whether any observed difference reflects more than chance variation.

The record also demonstrates why design labels require context. It identifies randomized allocation and single masking, yet classifies the model as single-group and does not explain how the listed dose and placebo groups were formed. The counts remain readable, but incomplete design details limit the strength of conclusions drawn from between-group comparisons.

Finally, the primary safety endpoint and serious-event summary answer related but distinct descriptive questions. Adverse events were recorded in each arm, while no serious adverse events were reported. Neither observation should be interpreted as a causal verdict or as proof about risks beyond the study. The statistical value of the record lies in its clearly bounded account of observed outcomes, together with recognizing what the registry does not report.

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.

Interpretation is constrained by the limited size of the listed arms, which range from 3 to 7 participants. With groups this small, the event count can change substantially in descriptive terms if a participant's outcome differs. The registry does not report confidence intervals or other uncertainty estimates for the primary endpoint, so its precision cannot be assessed from the posted result.

The primary outcome combines adverse events and serious adverse events. Although serious-event counts are separately available, the record does not provide event-level descriptions for the primary endpoint, severity detail for non-serious events, timing of individual events, or causal attribution. Death counts are not reported in the registry record.

The design description is incomplete for assessing comparisons: randomized allocation and single masking are recorded, alongside a single-group model, but procedures for allocation, masking and dose-cohort assignment are not reported. No two-arm analysis is posted, and the registry indicates that values are missing or not estimable for a binary two-arm comparison. The observed arm counts therefore do not support a formal comparative estimate.

The registry states that all 31 participants entered into the study received MEDI2338 or placebo and were included in the primary analysis, but does not describe missing-data handling, additional analysis populations, or sensitivity analyses. It also does not report the original sample-size justification, statistical-analysis plan, or multiplicity strategy. These are limitations of the information available in the registry record, not evidence that particular procedures were or were not used outside the record.

The study assessed single doses and reports a follow-up timeframe of Days 1 - 92 for the primary outcome. The results therefore do not characterize repeated dosing or outcomes beyond the stated period. Generalization to other populations or settings is not established by the posted counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety of MEDI2338 in Subjects With Chronic Obstructive Pulmonary Disease — NCT01322594.
• Registry record last updated 2013-10-23; status last verified 2013-10.
• Results first posted 2013-10-23.
• 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

This completed Phase 1 study evaluated single ascending intravenous doses of MEDI2338 in participants with stable, mild to moderate COPD. The registry lists randomized allocation, single masking and a single-group model. Enrollment was 31, and all participants entered into the study were stated to have received MEDI2338 or placebo and to have been included in the primary analysis.

The primary endpoint was the number of participants experiencing adverse events, including serious adverse events, during Days 1 - 92. The posted arm counts were 3 of 3, 3 of 3, 6 of 6, 7 of 7, and 5 of 6 across the MEDI2338 dose groups, and 6 of 6 for placebo. Serious adverse-event counts were 0 in each group.

No two-arm analysis or inferential result is posted. Details of the statistical plan, missing-data handling, multiplicity strategy and sample-size justification are not reported in the registry record. The results are descriptive observations from this study.