A Study to Evaluate the Effects of NST-4016 on QT/Corrected QT (QTc) Interval: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Effects of NST-4016 on QT/Corrected QT (QTc) Interval (NCT03577275), a randomized phase 1 study. The primary outcome is Change From Baseline in Fridericia's Correction for QT Interval (QTcF).

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, partially double-blind, placebo- and positive-controlled, four-way crossover study of icosabutate and electrocardiogram measures in healthy participants. The registry identifies the design model as crossover and records 32 enrolled participants. The posted results list 32 participants for each condition. In a crossover design, participants receive multiple treatment conditions, allowing comparisons to be made within participants as well as across treatment conditions. The sequence, timing between conditions, and handling of period or sequence effects are not reported in the registry record.

The four single-dose conditions were placebo, moxifloxacin 400mg, NST-4016 600mg, and NST-4016 2000mg. The registry describes the 600mg dose as likely therapeutic and the 2000mg dose as supratherapeutic. Moxifloxacin was an open-label active comparator; the study description says blinding applied except for moxifloxacin. The registry’s masking field says triple, while its narrative describes double blinding except for the positive control. The precise roles covered by the masking designation are not reported in the registry record.

The study is listed as completed, with a start date of 2018-06-15 and a primary completion date of 2018-09-15. Its objective was assessment of ECG effects, with QTcF as the primary endpoint and heart rate, QTcF, PR interval, and QRS interval among the posted outcomes. The registry record does not report the original sample-size justification, a detailed protocol, or the statistical model used for the sponsor’s primary analysis. The crossover structure matters when interpreting comparisons: a simple comparison treating each condition as independent may not use the within-participant design information. The recalculated comparisons described in the statistical interpretation are approximate unadjusted comparisons, not a reconstruction of a crossover-model analysis.

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: This was a cross over study so 32 subjects each completed 4 treatment arms

Overall Study

Analysis population for the primary outcome, as defined in the registry: The primary endpoint for this trial was the placebo corrected change from baseline in QTcF. The data presented here are the maximum absolute change from baseline for placebo, moxifloxacin 400mg, NST-4016 600mg and NST-4016 2000mg.

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 Fridericia's Correction for QT Interval (QTcF), measured over 24 hours.

The primary endpoint was the maximum absolute change from baseline in Fridericia’s correction for the QT interval, abbreviated QTcF, measured in milliseconds over 24 hours. The registry describes the primary question as the placebo-corrected change from baseline. The posted condition-level figures are least-squares means with standard errors; the reported condition values are -4.6 for placebo, 11.5 for moxifloxacin 400mg, -6.0 for NST-4016 600mg, and -6.1 for NST-4016 2000mg.

QT is an ECG interval, and QTcF is a version corrected for heart rate using Fridericia’s correction. General statistical context: heart rate can affect the measured QT interval, so a correction is used to make QT interval assessments more comparable across heart rates. The registry also lists change from baseline in heart rate separately, consistent with heart rate being relevant context for interpreting a corrected QT measure.

Maximum absolute change summarizes the largest absolute change over the stated assessment window rather than the average change at one specified moment. This endpoint is used to assess ECG effects across the observation period. The posted results do not state the full time-point schedule, the exact primary analysis model, or how the maximum was derived for participants with incomplete measurements. Those details are not reported in the registry record. The presented endpoint values and approximate placebo comparisons therefore describe the available summary statistics, rather than independently establishing the complete prespecified analysis.

7. Results Posted in the Registry

• Moxifloxacin 400mg: mean 11.50 versus -4.60 on control; difference 16.10 (95% CI 12.66 to 19.54), standardized effect d = 2.29; z-test p = <0.001.
• NST-4016 600mg: mean -6.00 versus -4.60 on control; difference -1.40 (95% CI -5.44 to 2.64), standardized effect d = -0.17; z-test p = 0.497.
• NST-4016 2000mg: mean -6.10 versus -4.60 on control; difference -1.50 (95% CI -5.58 to 2.58), standardized effect d = -0.18; z-test p = 0.471.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline in Heart Rate (HR)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Moxifloxacin 400mg: mean 12.20 versus 9.90 on control; difference 2.30 (95% CI -0.07 to 4.67), standardized effect d = 0.48; z-test p = 0.057.
  • NST-4016 600mg: mean 12.60 versus 9.90 on control; difference 2.70 (95% CI 0.29 to 5.11), standardized effect d = 0.55; z-test p = 0.028.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Moxifloxacin 400mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for NST-4016 600mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in Fridericia's Correction for QT Interval (QTcF)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Moxifloxacin 400mg: mean 11.50 versus -4.60 on control; difference 16.10 (95% CI 12.66 to 19.54), standardized effect d = 2.29; z-test p = <0.001.
  • NST-4016 600mg: mean -6.00 versus -4.60 on control; difference -1.40 (95% CI -5.44 to 2.64), standardized effect d = -0.17; z-test p = 0.497.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Moxifloxacin 400mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between NST-4016 600mg and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in PR Interval (PR)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Moxifloxacin 400mg: mean -11.90 versus -11.00 on control; difference -0.90 (95% CI -4.53 to 2.73), standardized effect d = -0.12; z-test p = 0.627.
  • NST-4016 600mg: mean -11.40 versus -11.00 on control; difference -0.40 (95% CI -4.11 to 3.31), standardized effect d = -0.05; z-test p = 0.833.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Moxifloxacin 400mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between NST-4016 600mg and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes cover heart rate, QTcF, PR interval, and QRS interval. Across the condition summaries, the heart-rate means are higher in the treatment conditions than in placebo, particularly for the 2000mg condition. The PR interval condition means are relatively similar. The secondary QTcF entry follows the broad pattern of a higher mean for moxifloxacin and values close to placebo for the icosabutate conditions, although its 2000mg condition mean differs from the primary endpoint entry. The registry does not provide a QRS result among the detailed secondary summaries.

These measurements provide context for the primary ECG question, but they are not interchangeable outcomes. Heart rate is relevant context for a corrected QT measure, while PR and QRS describe other ECG intervals. Their patterns do not resolve the uncertainty in the primary QTcF comparisons. The registry record lists one analysis count and includes no numerical results in the reported-analysis entry; it does not describe a comprehensive analysis plan for the secondary outcomes.

The secondary comparison figures are also unadjusted recalculations. For heart rate, the posted recalculations include a comparison with p = 0.028 for NST-4016 600mg and placebo, and p = 0.057 for moxifloxacin and placebo. Such values should be viewed cautiously in the setting of several outcomes and comparisons. Without a reported multiplicity strategy, the chance of observing at least one apparently notable result across repeated tests is not addressed. General statistical context: multiplicity adjustment or a prespecified hierarchy can help control the interpretation of multiple tests, but the registry record does not report which, if any, was used.

The secondary results are best treated as descriptive and exploratory unless supported by a prespecified analysis and a clear plan for handling multiple outcomes. They neither replace the primary endpoint nor demonstrate that a result on one ECG measure predicts a result on another. Secondary analyses and their multiplicity handling are not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline in Heart Rate (HR)
• Change From Baseline in Fridericia's Correction for QT Interval (QTcF)
• Change From Baseline in PR Interval (PR)
• Change From Baseline in QRS Interval (QRS)

9. Statistical Interpretation

10. Statistical Methods Explained

The registry posts continuous outcome summaries as least-squares means with standard errors. A mean describes the average value of a continuous measurement; a standard error describes the estimated precision of that mean. A smaller standard error generally indicates a more precise estimate, while a larger one indicates greater uncertainty about the mean. The standard error is not the same as the spread of individual participant measurements.

What is the reported comparison?

The posted comparison values are simple unadjusted recalculations from condition-level means and standard errors. For the primary QTcF endpoint, the comparisons use placebo as the reference condition. The mean differences and their confidence intervals are the recalculated contrasts, and the p-values are unadjusted. They should not be mistaken for sponsor-reported trial-model estimates. The registry’s reported-analysis entry does not contain a numerical analysis result or identify a method.

General statistical context: a mean difference expresses the estimated separation between two group means on the outcome’s original scale. A confidence interval describes uncertainty around that estimate under the assumptions of the calculation. A p-value summarizes how incompatible the observed data are with a specified null hypothesis under a statistical model; it is not the probability that the null hypothesis is true and does not measure the clinical importance of an effect. The recalculated p-values do not include an adjustment for multiple comparisons.

Why does the crossover design matter?

In a crossover trial, each participant receives more than one condition. Measurements from the same participant are usually correlated: factors specific to that participant can affect results under each condition. A suitable crossover analysis can use paired within-participant information and may account for treatment, period, and sequence. General statistical context: ignoring within-participant correlation can misstate the standard error, and treating the condition summaries as if they came from independent groups may fail to reflect the design. The available summary statistics do not provide the participant-level pairings or model details needed to reproduce a crossover analysis.

The recalculated comparisons use an approximate pooled standard deviation derived from the posted standard errors. That is a simplifying approximation, not a directly reported measure of individual-level variability. It does not restore the within-participant covariance information or establish that the sponsor used the same calculation. The trial’s own model, treatment sequence, period handling, covariance structure, and analysis population are not reported in the registry record.

How should the condition means be read?

The condition means provide descriptive summaries over the stated 24-hour timeframe. The standard errors attached to those means indicate uncertainty about their estimates, not the range containing most individual values. The primary outcome description refers to the maximum absolute change from baseline. As a result, the summary is about that endpoint definition and should not be interpreted as a time-by-time profile of QTcF or as a measure of every participant’s maximum.

The condition-level summary for the 2000mg condition is -6.1 in the primary endpoint entry. A separate secondary-outcome entry for QTcF lists -5.7 for that condition. The primary comparison and interpretation use the primary endpoint entry. The registry record does not explain the difference between those entries. The comparison figures for the primary endpoint are based on the primary entry’s condition values.

What can the p-values establish?

For the positive-control comparison, the recalculated p-value is < 0.001. For the two icosabutate comparisons, the recalculated p-values are 0.497 and 0.471. These unadjusted results are conditional on the simplified comparison method. They are not a report of the full study analysis. In particular, a nonsignificant result does not establish that two conditions are equivalent: equivalence requires a prespecified margin and an analysis designed to assess whether the uncertainty lies within that margin. Such a margin and an equivalence analysis are not reported in the registry record.

General statistical context: over-dispersion matters when outcome variation exceeds what a statistical model assumes. A model that understates variation may produce standard errors that are too small and confidence intervals that are too narrow. The primary endpoint is continuous, and the registry provides standard errors rather than participant-level distributions, so dispersion beyond those summaries cannot be assessed. The record does not identify a model or report diagnostics addressing this issue.

11. Confidence Intervals and Precision

The recalculated QTcF comparison for NST-4016 600mg versus placebo is -1.4 msec, with a 95% confidence interval from -5.437 to 2.637. For NST-4016 2000mg versus placebo, the estimate is -1.5 msec, with a 95% confidence interval from -5.577 to 2.577. Both intervals include zero. They also span values below and above zero, so the direction and size of a difference are not determined precisely by these calculations.

General statistical context: a confidence interval is a range of estimates compatible with the observed data under the calculation’s assumptions. Its width conveys precision: wider intervals indicate less precision. An interval containing zero means that zero difference is among the values compatible with the data under that method; it does not prove there is no difference. The intervals are based on simple unadjusted recalculations, not a reported crossover-model analysis. Their precision should be interpreted with that limitation in mind.

The positive-control comparison has an estimate of 16.1 msec and a 95% confidence interval from 12.66 to 19.54, with p < 0.001. This interval is entirely above zero under the approximate calculation. It is useful as a distinct comparison within the study, but does not by itself supply the missing sponsor analysis or establish the statistical properties of the planned method.

All three comparisons are based on 32 participants per condition in the posted summaries. The registry does not provide confidence intervals for the condition-level means, participant-level data, or the within-participant covariance needed to assess crossover-specific precision. It also does not report whether the estimates account for missing measurements. The intervals therefore describe the recalculated contrasts under their stated simplifying assumptions, not every source of uncertainty in the trial.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations, not the trial’s original design calculations. For these continuous outcomes, the figures are participants per arm. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The assumed effect to detect is the stated fraction of the observed effect. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column describes the number of participants per arm that the planning calculation indicates would be needed to have an 80% chance of detecting the specified effect under the stated assumptions. The 90% power column uses a higher target chance of detection and therefore gives a larger planned sample size for the same effect. These are prospective planning concepts, not probabilities that the completed study’s result is correct.

The rows use 100%, 75%, and 50% of the observed effect as alternative effects to detect. Smaller effects require more participants because they are harder to distinguish from random variation. For example, the planning figures for the 600mg QTcF comparison rise from 544 participants per arm for 80% power at 100% of the observed effect to 967 at 75% and 2,175 at 50%. The corresponding 90% figures are 728, 1,294, and 2,912. These examples illustrate how strongly required sample size depends on the assumed effect.

This is not observed power. The calculations are planning illustrations based on observed effects and simplified assumptions; they do not establish whether the study was adequately designed for its intended crossover analysis or explain its original enrollment target. The record’s sample-size justification is not reported.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 16.100; pooled standard deviation σ = 7.025.
2. n = 2 × (1.96 + 0.842)² × 7.025² / 16.100² = 3.0, rounded up to 3 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 16.1                      # observed difference in means
sigma <- 7.02543948803205                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3577275)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 3 (80% power), 5 (90% power)
 75% of observed effect: n per arm = 6 (80% power), 8 (90% power)
 50% of observed effect: n per arm = 12 (80% power), 17 (90% power)
power.t.test: 4.2 
Simulated power at n = 3 per arm: 0.564 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was handled. The study includes a primary outcome and several secondary ECG outcomes, and comparisons are available for multiple treatment conditions. When many outcomes or contrasts are examined, the chance of at least one statistically notable result can increase. General statistical context: a prespecified testing hierarchy, adjustment procedure, or clear designation of exploratory analyses can help readers understand how such results should be interpreted. No such approach is described in the registry record, so the recalculated p-values should be read as unadjusted.

The record also does not report whether interim analyses were planned or conducted, whether stopping rules were used, or whether any analysis was prespecified to address the crossover sequence or period. It does not give a detailed statistical analysis plan, model specification, or sponsor-reported numerical analysis for the primary endpoint. The original sample-size justification is not reported in the registry record.

Missing-data handling is not reported. The condition summaries list 32 participants per condition, but those counts alone do not show whether all measurements needed for the endpoint were available at every scheduled assessment. The record does not say how incomplete ECG measurements, withdrawals, or other unavailable outcome data were treated.

The analysis population is also not reported in enough detail to identify whether the posted results use all randomized participants, only participants who received each condition, or another defined population. In a crossover study, the number of participants contributing paired measurements and the treatment of incomplete sequences can affect the estimand and precision. These details are not available in the registry record. Consequently, the unadjusted recalculations cannot be taken as a reconstruction of the prespecified primary analysis, and secondary p-values warrant particular caution.

15. 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: cerebrovascular accident (3.1%).

The serious adverse event summaries list 32 participants at risk under each condition. There were no serious adverse events reported for placebo, moxifloxacin 400mg, or NST-4016 600mg. One serious adverse event was reported for NST-4016 2000mg. The registry lists cerebrovascular accident at 3.1% among the top serious-event terms. No deaths were reported in any condition.

These are counts recorded for the treatment conditions, not a complete account of the nature, timing, relatedness, or clinical course of every event. Because the design is crossover, the same participants may contribute to more than one condition; the condition-level counts should not be read as independent groups of unique people. The registry does not report a detailed event narrative or the sponsor’s assessment of causality. The absence of reported serious events in some conditions does not establish that such events cannot occur.

Other adverse events affected 4 participants in the placebo condition, 6 with moxifloxacin 400mg, 4 with NST-4016 600mg, and 15 with NST-4016 2000mg. These counts are separate from the serious-event summary and should not be combined with it. The safety figures describe what the registry record lists; they do not constitute medical advice or a complete safety assessment.

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

The posted QTcF condition means place the two icosabutate conditions near the placebo mean, while the positive-control mean is higher. The simple unadjusted recalculations likewise estimate small negative differences for icosabutate versus placebo and a positive difference for moxifloxacin versus placebo. The two icosabutate confidence intervals include zero and span differences in both directions. Under these approximate calculations, the data do not precisely establish the size or direction of a difference between either icosabutate condition and placebo.

This pattern is not proof of equivalence, and a nonsignificant p-value is not evidence that the true difference is exactly zero. An equivalence conclusion requires a prespecified margin and an analysis designed to test equivalence; neither is reported in the registry record. Likewise, the positive-control comparison’s interval being above zero under the approximate calculation does not replace the sponsor’s planned analysis. The registry does not provide the numerical primary analysis or identify the model used.

The study enrolled healthy participants and was a Phase 1, single-centre, four-way crossover study of single doses. The posted results therefore describe ECG measurements in this study population and design. They do not, by themselves, establish effects in other populations, with other dosing patterns, or over a different observation period. The timeframe for the primary endpoint is 24 hours.

The posted summaries should be distinguished from the full study evidence. The crossover analysis, participant-level data, missing-data approach, multiplicity plan, and original sample-size justification are not reported in the registry record. The recalculated intervals and p-values are simple unadjusted comparisons and do not incorporate the within-participant structure. The data can be described, but the record does not support a definitive conclusion about the trial’s prespecified inferential result. No medical recommendation follows from these registry summaries.

17. Why This Trial Matters Statistically

This study is statistically informative as an example of how design and reporting details shape interpretation. It uses a four-way crossover, so participants receive multiple conditions and within-participant comparisons may be central to an appropriate analysis. Yet the registry provides condition-level means and standard errors rather than paired data or a full crossover model. Simple recalculations from those summaries can describe contrasts, but they cannot recover the information about within-person correlation needed to reproduce the intended analysis.

The positive-control condition is also relevant to interpreting the measurement context: its posted QTcF mean differs from the placebo summary, whereas the icosabutate summaries are close to placebo. That descriptive pattern is useful, but the registry’s lack of a numerical sponsor analysis leaves uncertainty about how the trial’s primary question was formally evaluated. It illustrates why readers should distinguish descriptive statistics, recalculated comparisons, and the prespecified model result.

The study also demonstrates the importance of separating failure to detect a difference from evidence of equivalence. The icosabutate confidence intervals cross zero and allow values on either side. Without a reported equivalence margin and appropriate analysis, those results cannot establish that the conditions are equivalent to placebo. A planning illustration based on the observed effect also cannot be treated as observed power or as a justification for the original enrollment.

Finally, a registry record can contain useful outcome and safety summaries while leaving key analytical questions unanswered. Multiplicity handling, missing-data methods, analysis populations, interim analyses, and the original design assumptions are not reported. Recognizing those omissions is part of sound statistical reading: the posted data support a cautious description, while important details needed for a fuller inferential assessment remain unavailable.

18. 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.

Several limitations are specific to interpreting this registry record. First, the study is a crossover, but only condition-level summaries are available for the comparisons discussed. The paired participant-level measurements, treatment sequence, period information, and crossover model are not reported. The recalculated comparisons therefore do not capture the design’s within-participant structure and may not reproduce the planned analysis.

Second, the registry describes the primary endpoint as placebo-corrected, yet its reported-analysis entry contains no numerical estimate, interval, p-value, or method. The available inferential figures are unadjusted recalculations. The record does not explain whether the condition summaries or analyses were adjusted for baseline, period, sequence, or other terms.

Third, the primary endpoint entry lists -6.1 for the 2000mg condition, while a separate secondary QTcF entry lists -5.7. The primary endpoint comparison uses the primary entry, but the record does not explain the difference. Also not reported are the full assessment schedule, missing-data approach, analysis population, multiplicity strategy, interim analyses, or original sample-size justification.

Finally, the participants were healthy, the study was conducted at a single centre, and the treatment conditions were single doses observed over 24 hours for the primary endpoint. These features limit what the registry summaries alone can establish beyond this study setting. The safety summary does not provide detailed event descriptions or causality assessments. Each limitation calls for restraint in interpreting the results; none can be resolved from the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study to Evaluate the Effects of NST-4016 on QT/Corrected QT (QTc) Interval — NCT03577275.
• Registry record last updated 2019-11-04; status last verified 2019-10.
• Results first posted 2019-11-04.
• 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.

22. Record Summary

NCT03577275 is a completed Phase 1 randomized, four-way crossover study of icosabutate in healthy male and female participants. The registry records 32 enrolled participants and four single-dose conditions: placebo, moxifloxacin 400mg, NST-4016 600mg, and NST-4016 2000mg. The primary endpoint was maximum absolute change from baseline in QTcF over 24 hours.

Posted QTcF means were -4.6 msec for placebo, 11.5 msec for moxifloxacin, -6.0 msec for NST-4016 600mg, and -6.1 msec for NST-4016 2000mg. Simple unadjusted recalculations show the two icosabutate confidence intervals crossing zero. These are not sponsor-reported analyses and do not account for the crossover structure. The registry record does not report the primary analysis method, multiplicity plan, missing-data handling, analysis population, or original sample-size justification.