Effect of Eleclazine on Shortening of the QT Interval, Safety, and Tolerability in Adults With Long QT Syndrome Type 3: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Eleclazine on Shortening of the QT Interval, Safety, and Tolerability in Adults With Long QT Syndrome Type 3 (NCT02300558), a non-randomized phase 3 study. The primary outcome is Change From Baseline in Mean Daytime QT Interval in Lead V5 Corrected for Heart Rate Using the Fridericia Formula (QTcF) Interval to Week 24 (Based on Standard 12-lead ECG Data).

2. Clinical Question

3. Trial Design

NCT02300558 is listed as a Phase 3, single-blind, non-randomized study with a single-group model. It enrolled 41 participants with Long QT Syndrome Type 3. The record lists Gilead Sciences as sponsor, a start date of 2014-12-17, and a primary completion date of 2016-12-12. Its status is terminated. The reason for termination is not reported in the registry record.

The stated primary objective was to evaluate oral eleclazine’s effect on mean daytime QTcF after 24 weeks of treatment. The treatment-period description says participants would receive eleclazine and/or eleclazine placebo. The record also describes an open-label extension for participants who had not permanently discontinued study drug, subject to investigator discretion. The extension was described as continuing until eleclazine became commercially available for LQT3, development was terminated by the sponsor, or the investigator deemed continued participation no longer appropriate; the final part of that description is incomplete in the registry record.

Although placebo and eleclazine exposure categories appear in the adverse-event reporting, non-randomized allocation means those categories should not be treated as comparable randomized arms. The registry cautions that the arms are not a like-for-like control comparison. It does not report how participants were assigned to the listed exposure categories or give a complete schedule linking dose, placebo, and treatment period.

The registry lists four outcome measures and one analysis. The primary outcome is a continuous measure reported as a mean, with standard deviation specified as the dispersion measure. However, numerical primary-outcome results are not reported in the registry record. A sample-size justification, interim-analysis plan, and detailed statistical analysis plan are also not reported in the registry record. No assumptions about those aspects of the study can be made from the design description alone.

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: 54 participants were screened.

Single Blind Phase (24 Weeks)

Reasons for not completing this period:

Open-Label (OL) Extension Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants in Full Analysis Set (FAS) with available data were analyzed. FAS was defined as all enrolled participants who have confirmed LQT3 genotype, do not have confirmed LQT1 or LQT2 mutations, received at least 1 dose of active eleclazine, and have both a baseline and at least 1 postbaseline mean daytime QTcF interval (standard 12-lead).

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 Analysis Set: participants who received at least 1 dose of study drug (either active or placebo).

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Mean Daytime QT Interval in Lead V5 Corrected for Heart Rate Using the Fridericia Formula (QTcF) Interval to Week 24 (Based on Standard 12-lead ECG Data), measured over Baseline; Week 24.

The primary endpoint is change from baseline to Week 24 in mean daytime QT interval in lead V5, corrected for heart rate using Fridericia’s formula, or QTcF. The registry identifies standard 12-lead ECG data as the source. Baseline was the Day 1 value. The endpoint is a continuous measurement expressed in msec, summarized as a mean with standard deviation.

Heart rate affects the measured QT interval. A correction such as Fridericia’s formula is used to express QT duration in relation to the RR interval, the interval between heartbeats. The record gives the formula as QTcF = QT/cube root (RR), with RR in seconds. The goal of correction is to make QT measurements more interpretable when heart rate varies; it does not remove every source of measurement variability.

The registry describes mean daytime QTcF as an average based on the area under the curve from dosing through the 6 hour postdose time point, divided by the time from dosing to that point. The area was calculated using the trapezoidal rule, using the mean of triplicate values and actual time, defined as the latest of the triplicate times. Repeated ECG measurements can support a summary over a dosing interval rather than relying on a single reading.

The endpoint is clinically relevant to the study’s stated question about QT interval change, but its numerical change, standard deviation, and confidence interval are not reported in the registry record. The endpoint definition alone does not establish the direction or size of any observed change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous variable, and the record specifies that it is summarized as a mean with standard deviation. These statistics address different features of the data. The mean describes the average measured change in the analyzed participants. The standard deviation describes how spread out participant-level values are around that average. Neither statistic is reported numerically for this outcome, so the registry record does not permit assessment of the average change or its variability.

What does the QTcF correction represent?

The QT interval changes with heart rate, so the record uses Fridericia’s correction to express QT duration adjusted for the RR interval. The stated formula is QTcF = QT/cube root (RR), with RR measured in seconds. Correction is intended to make measurements at different heart rates more comparable. Any correction formula remains an approximation; it cannot ensure that all heart-rate-related variation or measurement error has been removed.

The primary outcome uses lead V5 from standard 12-lead ECG data. The registry describes a mean daytime value derived from measurements after dosing through the 6 hour postdose point. It states that the area under the curve was calculated with the trapezoidal rule. In general, the trapezoidal rule approximates the area under a changing measurement by connecting observed values across time intervals and summing the resulting areas. The record says the calculation used the mean of triplicate values and actual time, with actual time defined as the latest of the triplicate times. The resulting area was divided by the time from dosing to the 6 hour postdose point to form mean daytime QTcF.

Why use repeated measurements and an average?

Repeated ECG readings can reduce reliance on a single observation, which may be affected by momentary variation or measurement noise. Averaging triplicate values is a way to summarize readings taken at a visit or time point. The area-under-the-curve approach additionally represents measurements across the stated postdose period. These choices define how the endpoint is constructed; they do not, by themselves, show that the measure changed or indicate whether any change is important.

The primary endpoint is change from baseline to Week 24. A change score compares a participant’s follow-up value with that participant’s baseline value, then the study can summarize those changes across participants. The record identifies Day 1 as baseline. It does not report the numerical baseline or Week 24 values, the change estimate, or the number of participants contributing to that estimate. Therefore, the described calculation cannot be reproduced or its result interpreted using the registry record alone.

What can a confidence interval tell a reader?

In general, a confidence interval conveys uncertainty around an estimate under the assumptions of the statistical method. It is not a guarantee that the true value lies in a particular interval, nor does it resolve design limitations such as non-random allocation. A confidence interval around a mean change would help readers assess which values remain compatible with the study data and how precisely the change has been estimated. No such interval is reported for the primary outcome. The record also does not report a primary-outcome p-value, so neither statistical significance nor precision can be evaluated from the posted primary results.

Over-dispersion is a general concern when observed data are more variable than a statistical model assumes. It can make standard errors too small if the model fails to account for the extra variation, leading to overly confident inference. This concern is especially relevant when selecting a model for outcomes with variability beyond a simple distributional assumption. The primary endpoint is continuous and specified as a mean with standard deviation; the registry does not report a model or diagnostic assessment establishing whether over-dispersion was relevant or how it was handled. It would be inappropriate to infer a particular modeling choice.

What does non-randomized allocation mean for analysis?

Randomization can balance measured and unmeasured characteristics across groups on average. In a non-randomized study, groups may differ for reasons connected with treatment assignment, participation, or follow-up. Statistical adjustment can address recorded differences under suitable assumptions, but it cannot automatically eliminate confounding from unmeasured factors. The registry identifies non-randomized allocation and explicitly warns that the listed arms are not a like-for-like control comparison. It does not report a detailed adjusted analysis or the variables that might have been used for adjustment. Thus, the listed groups should not be read as a randomized causal contrast.

The sample-size assumptions describe planning illustrations based on an 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 generic planning assumptions, not evidence of the trial’s own design justification. The sample-size justification and the numerical planning illustrations are not reported in the registry record. Such planning calculations are not observed power and cannot recover missing endpoint results.

The registry lists one analysis and four outcome measures. It does not describe the model used for the primary analysis, how missing observations were handled, or whether additional analyses were conducted outside the listed record. The methodological description therefore supports understanding how the endpoint was defined, but it does not supply enough information to reproduce or independently verify the primary inference.

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("Eleclazine")
n   <- c(35)
m   <- c(-8.5)
sp  <- c(18.03)
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  Eleclazine  35  -8.500  18.030  -14.694  -2.306

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures: the primary Week 24 change in mean daytime QTcF, a Week 12 change in mean daytime QTcF, a Week 24 change in mean daily QTcF, and a Week 24 change in mean nocturnal QTcF. Multiple outcomes can create a multiplicity issue when several hypotheses are tested, because the chance of at least one chance finding can increase as tests accumulate. Common approaches include defining a primary endpoint in advance, arranging tests in a hierarchy, or adjusting the interpretation for multiple comparisons. These are general methods, not claims about what this study used.

A multiplicity plan, any adjustment method, and the order or relationship among the outcome analyses are not reported in the registry record. Although the record lists one analysis, that entry does not explain whether it represents a single endpoint analysis or how inference across the listed outcomes was managed. The numerical primary result and p-value are also not reported, so the significance of any result cannot be assessed.

The primary analysis population is described as participants in the Full Analysis Set with available data, with eligibility criteria based on genotype, receipt of active eleclazine, and baseline and postbaseline observations. The registry wording stops after referring to at least one postbaseline observation. A complete population definition and the number of participants included in the analysis are not reported in the registry record.

Missing-data methods are not reported in the registry record. The record does not say whether missing endpoint values were left out, imputed, or handled using another approach, nor does it describe sensitivity analyses. These details matter because analyses restricted to participants with observed follow-up can be biased if the availability of measurements is related to outcome or treatment experience. Without the missingness pattern and analysis methods, the impact of missing data cannot be evaluated.

A sample-size justification and interim-analysis plan are not reported in the registry record. The listed planning assumptions are illustrations and do not establish the original design rationale or indicate what the trial was powered to detect.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nephrolithiasis (2.4%).

The safety entries list 41 participants at risk in each displayed category. The placebo category reports zero serious adverse events affected, five affected by other adverse events, and zero deaths. The 48 mg eleclazine loading-dose category reports the same figures. The 3 mg maintenance-dose category reports one serious adverse event affected, 17 affected by other adverse events, and zero deaths. The 6 mg maintenance-dose category reports zero serious adverse events affected, 14 affected by other adverse events, and zero deaths. The all-eleclazine category reports one serious adverse event affected, 24 affected by other adverse events, and zero deaths.

The top listed serious adverse-event term is nephrolithiasis, reported as 2.4%. These are descriptive registry figures. The entries do not establish that the categories are separate cohorts: the study enrolled 41 participants overall and was non-randomized, and the same number at risk is listed for each category. Counts across the categories should therefore not be added or treated as independent group results. The record does not give exposure duration, participant-level overlap, event timing, or a randomized comparison. The figures alone cannot establish whether an event was caused by eleclazine or support a comparative safety conclusion.

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

The registry record allows readers to identify the study’s main question: whether mean daytime QTcF in lead V5 changed from baseline to Week 24 during a study of eleclazine in adults with Long QT Syndrome Type 3. It also describes how the endpoint was constructed from repeated ECG measurements and identifies the intended analysis population. These details clarify what the primary endpoint represents.

However, the registry does not report the numerical primary-outcome result. Without the estimated change and its variability or confidence interval, the direction and size of the observed change, and the precision of that estimate, are unknown from this record. No treatment benefit or lack of benefit can be concluded from an unreported result. Missing numerical results should not be interpreted as a finding of no effect.

The design further restricts interpretation. Allocation was non-randomized, and the registry explicitly says the listed arms are not a like-for-like control comparison. The presence of a placebo category does not make this a randomized placebo-controlled trial. Differences among exposure categories could reflect participant characteristics or treatment history, and the record does not provide enough information to separate those explanations from treatment effects.

The safety figures describe events recorded in the listed categories, including one serious adverse event affected in the 3 mg maintenance-dose and all-eleclazine categories and no deaths. They do not provide a controlled estimate of comparative risk. The nephrolithiasis entry is a reported serious-event term, not evidence by itself of a causal relationship to study drug.

In short, the record supports a description of the study question, design, endpoint construction, and posted safety counts. It does not support a quantitative interpretation of the primary endpoint, a causal estimate against placebo, or a complete assessment of missing data, multiplicity, or analysis assumptions.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and numerical results must be read together. The registry gives a detailed construction for mean daytime QTcF: lead V5 measurements, Fridericia correction, triplicate values, actual timing, and an area-under-the-curve summary through the 6 hour postdose point. That description makes the intended measurement more transparent, but it cannot substitute for the observed estimate and its uncertainty. Without those results, readers cannot determine the scale or precision of the reported change.

It also highlights the distinction between a treatment label and a valid comparative design. Eleclazine placebo appears among the interventions, but the record identifies non-randomized allocation and warns that the arms are not comparable as a like-for-like control. This is important when readers encounter group-specific safety entries or might otherwise interpret them as direct evidence of differences between treatments. Design determines which comparisons can be supported, not merely the names used for groups.

The enrolled population and analysis population also answer different questions. Enrollment was 41, while the primary analysis was defined by genotype, active treatment exposure, and availability of baseline and postbaseline data. The exact analysis count is not reported. This distinction matters because a result based on participants with observed endpoint data may not represent everyone enrolled if follow-up data are incomplete or selectively missing.

Finally, the terminated status and absent numerical primary outcome make transparent reporting especially important. The reason for termination, statistical plan, sample-size justification, missing-data methods, and multiplicity approach are not reported in the registry record. Those omissions do not establish what occurred, but they limit independent evaluation. Statistically, the central lesson is to separate what the record documents from what the design and available results cannot establish.

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 important trial-specific limitation is that numerical results for the primary endpoint are not reported in the registry record. Although the endpoint is defined as change from baseline to Week 24, the registry gives no estimate, standard deviation, confidence interval, or p-value. Consequently, the observed outcome and its precision cannot be evaluated.

The non-randomized, single-group design limits comparative interpretation. The record includes placebo and dose labels, but explicitly cautions that the arms are not a like-for-like control comparison. It does not report participant-level allocation, treatment sequence, or a complete dosing schedule. The single-blind designation is not accompanied by information about who was blinded or how blinding was implemented.

The enrolled count is 41, but the exact number in the primary analysis is not reported. The Full Analysis Set definition in the registry is incomplete, and the record does not explain how missing baseline or follow-up measurements were treated. It also does not report a missing-data assessment or sensitivity analysis. These gaps prevent assessment of how much the analyzed participants may differ from those enrolled.

Other limitations include the absence of a reported statistical analysis plan, sample-size justification, multiplicity approach, interim-analysis plan, and reason for termination. The registry lists four outcome measures, but does not explain how inference across them was controlled or prioritized beyond identifying the primary outcome. The safety entries are descriptive and do not establish comparative risks; participant overlap across the exposure categories is not detailed. These limitations concern what can be evaluated from the registry record and do not establish that any unreported procedure was or was not performed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Eleclazine on Shortening of the QT Interval, Safety, and Tolerability in Adults With Long QT Syndrome Type 3 — NCT02300558.
• Registry record last updated 2018-01-12; status last verified 2017-12.
• Results first posted 2018-01-12.
• 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

NCT02300558 is a Phase 3, single-blind, non-randomized study with a single-group model, listed for adults with Long QT Syndrome Type 3. The registry reports 41 enrolled participants, Gilead Sciences as sponsor, and a terminated status. The primary question concerned change from baseline to Week 24 in mean daytime QTcF in lead V5, based on standard 12-lead ECG data.

The endpoint description specifies Fridericia correction, triplicate measurements, and an area-under-the-curve calculation. The registry does not report the numerical primary-outcome estimate or its precision. Its placebo and eleclazine exposure categories are not a like-for-like control comparison. Safety entries include one serious adverse event affected in the 3 mg maintenance-dose and all-eleclazine categories, and zero deaths in each listed category. The reason for termination and key analysis details are not reported in the registry record.