A Study to Evaluate the Effect of MCI-186 at Therapeutic and Supra-Therapeutic Doses on the QT Interval(QT)/Corrected QT Interval(QTc) Interval in Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Effect of MCI-186 at Therapeutic and Supra-Therapeutic Doses on the QT Interval(QT)/Corrected QT Interval(QTc) Interval in Healthy Subjects (NCT04029090), a randomized phase 1 study. The primary outcome is Change From Baseline in QTcF(ΔQTcF) With Placebo Adjustment (ΔΔQTcF) at Cmax of MCI-186.

2. Clinical Question

3. Trial Design

This was a phase 1, randomized, three-way crossover study in healthy subjects. Its official title describes a placebo-controlled study of therapeutic and supra-therapeutic doses. The registry lists the model as crossover and enrollment as 27. In a crossover design, participants receive more than one assigned treatment over the course of a study, so comparisons can be made across treatment periods within participants. That general feature can make each participant informative under multiple conditions, but interpretation also depends on the conduct and analysis of the periods.

The three listed sequences varied the order of Treatment A, Treatment B, and Treatment C. Treatment A was 60 mg of MCI-186, Treatment B was 300 mg of MCI-186, and Treatment C was 0.9% w/v saline. Each sequence description specifies a single intravenous dose delivered as a 1-hour infusion at each treatment. The posted primary endpoint description concerns a regression relationship between change in QTcF and MCI-186 concentration at matching post-dose times, with adjustment for placebo treatments.

The record lists the study as randomized and its masking as double. The official title, however, calls it single-blind. The registry record does not explain this difference, so the masking description cannot be resolved from the posted information. The study is marked completed. Its listed start date is 2018-09-18 and its primary completion date is 2018-10-20.

Secondary outcomes included heart rate, PR interval, QRS interval, QTcF by timepoint, plasma concentration, pharmacokinetic measures, and adverse events. These outcomes provide context about what else the study planned to assess, but the presence of an outcome in the registry does not by itself establish that a result was posted. The record lists eight posted secondary outcomes and does not include analysis entries. Details of treatment-period spacing, washout, sequence allocation, and the statistical handling of period or sequence effects 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received 600mg, and 300mg of MCI-186 were included in the analysis. One participant on 300mg was not included due to meeting the exclusion criteria (Protocol Violation). Overall Number of Participants Analyzed was entered as the number at the time of calculation of Cmax.

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.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in QTcF(ΔQTcF) With Placebo Adjustment (ΔΔQTcF) at Cmax of MCI-186, measured over 45 min pre-dose to 24 h post-dose.

The primary endpoint is change from baseline in QTcF, adjusted for placebo, at the maximum plasma concentration of MCI-186. QTcF is the QT interval corrected for heart rate using Fridericia's formula. The registry describes the endpoint as ΔQTcF with placebo adjustment, or ΔΔQTcF, and gives the unit as milliseconds. Its stated timeframe runs from 45 min pre-dose to 24 h post-dose.

The endpoint uses change from baseline to focus on the difference from each participant's starting measurement rather than relying only on measurements after dosing. Placebo adjustment is intended to account for changes observed during placebo treatment, while the concentration-response analysis relates QTcF changes to MCI-186 concentrations measured at matching times. This is the analysis approach described in the registry record; details beyond that description are not reported there.

The endpoint is used to characterize the estimated QTcF change associated with the studied doses and concentrations. It does not, by itself, answer every question about cardiac safety, other outcomes, or effects in people who were not studied. The posted estimates are accompanied by 90% confidence intervals, which show the uncertainty around each estimate under the analysis used. The registry record does not report a decision threshold for this endpoint or a separate formal conclusion about whether the estimates meet such a threshold.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary analysis is described as a regression relationship between ΔQTcF and MCI-186 concentration at matching times after dosing, with adjustment for placebo treatments. The registry reports dose-specific estimates and 90% confidence intervals. It does not report the complete statistical model, parameterization, covariance structure, handling of repeated measurements, or diagnostic checks. Those details matter for understanding exactly how the estimates were produced, especially when measurements are collected across time and treatment periods.

What does a confidence interval communicate?

General statistical explanation: A confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. Its endpoints are not a guarantee that the true value lies within that particular interval, and the interval does not indicate the probability that a treatment effect is present. A narrower interval usually represents greater precision than a wider interval, all else being comparable. Here, the registry gives 90% confidence intervals for the primary endpoint: -1.5 to 0.5 ms for MCI-186 60mg and -1.0 to 1.9 ms for MCI-186 300mg. Both intervals include zero, so the posted results do not isolate a direction of change at the level of the interval alone.

Why use placebo adjustment?

General statistical explanation: Placebo adjustment is a way to distinguish changes associated with active treatment from changes that may also occur during a control condition. The registry says that the primary endpoint was based on a concentration-response analysis and included adjustment for placebo treatments. That description establishes the intended role of placebo in the analysis, but it does not show the model equation or the exact calculation used for each estimate. The posted primary results list the two MCI-186 dose estimates; a separate placebo estimate is not included in the results.

How does the crossover design affect interpretation?

General statistical explanation: In a crossover study, participants receive treatments in different periods, and comparisons may use information from the same participant under more than one treatment. This can account for stable differences between participants, but treatment order and changes over time can also matter. The registry lists three treatment sequences and a crossover model. It does not report the period-specific analysis, washout details, tests for carryover, or how sequence effects were handled. These omissions prevent a complete reconstruction of the analysis from the registry record.

The listed sequence descriptions identify the treatment order: MCI-186 60mg, MCI-186 300mg, and saline appear in differing orders. The primary analysis description refers to matching concentration and QTcF observations after dosing and to placebo adjustment. The record does not state whether the analysis used participant-level random effects, a particular repeated-measures covariance structure, or a specific method for estimating uncertainty. Those are not details that can be inferred merely from the fact that the study was crossover.

What is the role of concentration-response analysis?

General statistical explanation: A concentration-response analysis relates measured drug concentration to an outcome, rather than relying only on treatment labels or dose groups. Matching concentration and outcome measurements can be informative when concentrations vary over time. The registry states that this relationship was used for ΔQTcF and that placebo treatments were included in the adjustment. It does not provide the fitted slope, model form, concentration values, or other model outputs in the information. The reported primary estimates are at Cmax, but the record does not provide enough detail to reproduce them independently.

The registry lists the primary measure as a mean and the dispersion as a 90% confidence interval. The dose-specific estimates are -0.5 ms for 60mg and 0.5 ms for 300mg. The confidence intervals are -1.5 to 0.5 ms and -1.0 to 1.9 ms, respectively. These are the posted quantities; no recalculated estimates are needed to describe them. No direct dose-to-dose contrast is reported in these results.

The analysis population description says that participants who received 600mg and 300mg of MCI-186 were included, and notes that a participant on 300mg was excluded because of a protocol violation. The reported 60mg result lists 27 participants, while the 300mg result lists 26. The registry does not clarify the reference to 600mg in relation to the treatment sequences, which list 60mg and 300mg as the active doses. This ambiguity should be retained rather than resolved by assumption.

The sample-size material accompanying the page is a planning illustration based on the observed effect, using the stated assumptions for significance level, allocation, and approximation. Such illustrations ask how many participants per arm might be needed under chosen assumptions; they are not evidence about the original design's planning rationale and are not observed power. The registry record does not report the original sample-size justification. No sample-size target or interim analysis plan can be inferred from the enrollment alone.

Finally, statistical significance, clinical importance, and precision are different concepts. The confidence intervals describe precision under the analysis, while a significance test would require a stated null hypothesis and decision procedure. Clinical interpretation would require a relevant threshold or context. The registry record does not report a threshold for the primary QTcF endpoint, a p-value for the posted estimates, or a formal equivalence framework. The responsible statistical reading is therefore to describe the estimates and intervals without converting them into a claim that a threshold was met or ruled out.

10. Multiplicity, Missing Data and Analysis Populations

The study lists a primary endpoint and several secondary outcomes, including heart rate, PR interval, QRS interval, QTcF by timepoint, plasma concentration, pharmacokinetic measures, and adverse events. When a study assesses multiple outcomes, timepoints, doses, or contrasts, there may be multiple opportunities to identify an apparently notable result. Statistical methods can address this through prespecified testing sequences or adjustments, but the registry record does not report a multiplicity strategy. It also does not report whether secondary outcomes were treated as exploratory or confirmatory.

Although the primary endpoint spans 45 min pre-dose to 24 h post-dose, the primary estimate is described at Cmax. The registry says the analysis related QTcF change to concentration at matching times, but does not give the complete timepoint-selection or modeling plan. It is therefore not possible to determine from this record how choices across timepoints were handled, or whether any interim analyses were planned. Interim analyses are not reported in the registry record.

The analysis population description identifies a protocol-violation exclusion for a participant on 300mg. It does not fully describe missing measurements, reasons for missingness, imputation, or sensitivity analyses. The registry record does not report whether any endpoint observations were missing or how such observations were handled. The primary counts are 27 for 60mg and 26 for 300mg, but those counts alone do not explain completeness across all crossover periods.

The posted record also does not supply a full statistical analysis plan, model specification, prespecified decision threshold, or details of analysis-set definitions. These omissions limit evaluation of whether the posted analysis followed a prespecified plan and how robust the results are to alternative assumptions. They do not change the numerical estimates displayed, but they constrain what can be concluded from them.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety summary lists serious adverse events for each treatment group. For MCI-186 60mg, 0 of 27 participants at risk were listed as affected; for MCI-186 300mg, 0 of 26; and for placebo, 0 of 25. The table also lists 0 deaths for each group. These are the reported serious-event figures in the registry record. They should be read as counts within the recorded groups, not as proof that serious events are impossible or that all safety risks have been excluded.

The record separately lists 1 participant with other adverse events in each group: 1 of 27 for MCI-186 60mg, 1 of 26 for MCI-186 300mg, and 1 of 25 for placebo. The registry does not provide event terms in the serious-event summary, and the displayed information does not describe the nature, timing, or severity of the other events. The group counts also should not be interpreted as a direct comparison of risk without information about definitions, exposure, period handling, and the analysis used.

Because the design was crossover, participants could receive multiple treatments in different sequences. The registry record does not explain in detail how adverse events were attributed across treatment periods. These counts are a compact record summary, not a complete safety analysis or a basis for medical advice.

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

The posted primary results describe two placebo-adjusted estimates at Cmax: -0.5 ms for MCI-186 60mg and 0.5 ms for MCI-186 300mg. Their respective 90% confidence intervals are -1.5 to 0.5 ms and -1.0 to 1.9 ms. Each interval includes zero, so neither estimate is isolated from zero by the interval as posted. The intervals also extend in both directions, which is a reminder that the point estimate alone does not show the full uncertainty.

These results do not prove that the true effect is zero. They also do not establish equivalence, rule out a meaningful effect, or show that one dose differs from the other. Those conclusions would require a prespecified decision framework, a relevant margin or direct contrast, and the corresponding analysis. The registry record does not report these items. No dose-to-dose difference is calculated.

The endpoint is specific: a placebo-adjusted change from baseline in QTcF, using Fridericia correction, based on a concentration-response analysis and reported at Cmax. It is not a summary of every cardiac measure or every secondary outcome. The registry lists other outcomes, but the results do not include estimates for all of them. A listed outcome should not be treated as a result unless its numerical result is posted.

The trial enrolled healthy subjects and was a phase 1 study. That context is essential: the estimates characterize the study population, intervention conditions, and analysis described in the registry. The record does not establish how results would apply to other populations or treatment settings. Nor does the posted statistical result, by itself, answer a clinical decision question.

In short, the record reports estimates close to zero with confidence intervals that cross zero, alongside limited detail about the full analysis plan. The appropriate reading is descriptive and bounded by what is posted. It is not a claim that MCI-186 does or does not cause a particular clinical outcome.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it combines a crossover design with a concentration-response endpoint. The sequence descriptions show that participants received the active doses and saline in varying orders. The primary analysis then related change in QTcF to measured concentration at matching times and adjusted for placebo treatments. This illustrates how a study can use both treatment-period structure and measured exposure to frame its primary question.

The result also shows why point estimates should be read together with uncertainty. The posted estimates are -0.5 ms for 60mg and 0.5 ms for 300mg, but each is accompanied by a 90% confidence interval that includes zero. Reporting the interval makes the precision visible and discourages treating a single estimate as an exact value. It does not, however, answer whether a predefined threshold was met, because such a threshold is not reported in the registry record.

The record highlights the value of transparent analysis reporting. It names a regression relationship, placebo adjustment, the analysis population, and a protocol-violation exclusion. At the same time, it does not report the full model, missing-data handling, multiplicity strategy, or sample-size justification. Those details are needed to assess the analysis more completely and to understand what assumptions support the estimates.

Finally, the crossover label and the differing masking descriptions call for careful reading rather than assumption. The registry lists double masking, while the official title says single-blind; the record does not explain the difference. Statistical interpretation benefits from keeping such record-level ambiguities visible. The posted estimates can be described accurately without claiming more certainty or detail than the record supports.

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 registry record contains limited information for reproducing the primary analysis. It describes a regression relationship between ΔQTcF and concentration at matching times, with placebo adjustment, but does not report the full model, parameter estimates beyond the posted dose results, or diagnostics. Details about repeated observations, period and sequence effects, and the handling of crossover structure are not reported in the registry record.

There is a difference between the masking descriptions: the registry lists double masking, while the official title describes the study as single-blind. The registry record does not resolve this. The analysis population description also refers to participants who received 600mg and 300mg, while the sequence descriptions identify 60mg and 300mg as the active doses. The record does not clarify this reference, so it should not be silently reconciled.

The primary result listing gives dose-specific estimates and confidence intervals, but no separate placebo estimate or direct contrast between active doses is included in the results. A decision threshold, formal equivalence margin, and p-values for these estimates are not reported. The record also does not report the original sample-size justification, interim analyses, a multiplicity plan, missing-data methods, or sensitivity analyses.

The trial enrolled healthy subjects, and the displayed enrollment was 27. The primary outcome counts are 27 for 60mg and 26 for 300mg, with the record noting a protocol-violation exclusion on 300mg. Information about missing observations across treatment periods is not reported. These limitations constrain interpretation of both precision and generalizability without changing the numerical results that are posted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Effect of MCI-186 at Therapeutic and Supra-Therapeutic Doses on the QT Interval(QT)/Corrected QT Interval(QTc) Interval in Healthy Subjects — NCT04029090.
• Registry record last updated 2026-07-15; status last verified 2026-06.
• Results first posted 2024-11-21.
• 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

This completed phase 1 study was randomized and used a three-way crossover design in healthy adult subjects. The registry lists enrollment of 27 and describes intravenous MCI-186 infusions at 60mg and 300mg, with 0.9% w/v saline as placebo. Its primary question concerned placebo-adjusted change from baseline in QTcF at Cmax, using a concentration-response analysis.

The posted estimate for MCI-186 60mg is -0.5 ms, with a 90% confidence interval from -1.5 to 0.5 ms and 27 participants. For MCI-186 300mg, the estimate is 0.5 ms, with a 90% confidence interval from -1.0 to 1.9 ms and 26 participants. Both intervals include zero. Serious adverse events and deaths are listed as 0 in each treatment group.

The registry record does not report the complete statistical model, multiplicity approach, missing-data methods, or original sample-size justification. The results should be read as estimates for the studied population and analysis, with those reporting limits in view.