This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of Effect of Selpercatinib (LY3527723) on Corrected QT (QTc) Interval in Healthy Participants (NCT05630274), a randomized phase 1 study. The primary outcome is Cardiodynamics: Placebo-corrected Change From Baseline in QT Interval Corrected Using Fridericia's Correction (QTcF) (ΔΔQTcF) for Treatments A, B, and C.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05630274 |
| Phase | Phase 1 |
| Condition | Healthy |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 32 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
Healthy adult participants were enrolled. The primary analysis population comprised randomized participants who received at least one dose of selpercatinib or moxifloxacin, had baseline measurements, and had at least one post-dose time point with a valid change in QTc value.
Intervention
The study assessed selpercatinib at 320 mg and 640 mg. Treatment A was 320 mg selpercatinib with matching placebo; Treatment B was 640 mg selpercatinib.
Comparator
The comparison conditions were selpercatinib-matching placebo and 400 mg moxifloxacin. Moxifloxacin was included as a positive control in the randomized, double-blind, four-way crossover study.
Primary question
How did the placebo-corrected change from baseline in QTcF differ after Treatments A, B, and C? QTcF is the QT interval corrected for heart rate using Fridericia’s correction. The registry reports least-squares mean estimates and 90% confidence intervals.
The primary outcome concerns an electrocardiographic measure of cardiac electrical timing, not a clinical event. ECG recordings were assessed at pre-dose and specified post-dose times through 24 hours. The study was conducted in healthy participants, so its primary question is a controlled assessment of QTcF measurements under the study conditions. The registry record does not report a clinical outcome question or results for a patient population with a health condition.
3. Trial Design
This completed Phase 1 study used randomized, double-blind, placebo- and positive-control, four-way crossover design. The registry lists an enrollment of 32 and describes four treatment sequences: ABCD, BDAC, CADB, and DCBA. Across the sequence descriptions, participants were assigned different orders of Treatment A, Treatment B, Treatment C, and Treatment D. Treatment A was 320 mg selpercatinib with matching placebo; Treatment B was 640 mg selpercatinib; Treatment C was 400 mg moxifloxacin; and Treatment D was selpercatinib-matching placebo.
A crossover design assesses treatments within a sequence of treatment periods rather than assigning every participant to just one condition for the whole study. Randomizing treatment order can help limit the influence of order on comparisons, while blinding is intended to keep treatment knowledge from influencing conduct or assessment. These are general features of the design; details of how the study handled period effects, carryover, or sequence effects are not reported in the registry record.
The registry lists the study start as 2019-04-16 and primary completion as 2019-06-21, with status completed. The brief summary says the study would last up to 41 days. The registry record does not report a sample-size justification or provide further detail about the timing and conduct of each treatment period. The primary outcome population required a baseline measurement and at least one valid post-dose change measurement after dosing with selpercatinib or moxifloxacin.
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: Participants were randomized to 4 treatment sequences (ABCD, BDAC, CADB, and DCBA), with each sequence having 4 periods where participants were crossed over between the periods. There was a washout period of 10 days between dosing in each period.
Treatment Period 1
| Stage | Treatment Sequence 1: ABCD | Treatment Sequence 2: BDAC | Treatment Sequence 3: CADB | Treatment Sequence 4: DCBA |
|---|---|---|---|---|
| STARTED | 8 | 8 | 8 | 8 |
| Received at Least One Dose of Study Drug | 8 | 8 | 8 | 8 |
| COMPLETED | 8 | 8 | 8 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Treatment Period 2
| Stage | Treatment Sequence 1: ABCD | Treatment Sequence 2: BDAC | Treatment Sequence 3: CADB | Treatment Sequence 4: DCBA |
|---|---|---|---|---|
| STARTED | 8 | 8 | 8 | 8 |
| Received at Least One Dose of Study Drug | 8 | 8 | 8 | 8 |
| COMPLETED | 8 | 8 | 8 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Treatment Period 3
| Stage | Treatment Sequence 1: ABCD | Treatment Sequence 2: BDAC | Treatment Sequence 3: CADB | Treatment Sequence 4: DCBA |
|---|---|---|---|---|
| STARTED | 8 | 8 | 8 | 8 |
| Received at Least One Dose of Study Drug | 8 | 8 | 8 | 8 |
| COMPLETED | 8 | 8 | 8 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Treatment Period 4
| Stage | Treatment Sequence 1: ABCD | Treatment Sequence 2: BDAC | Treatment Sequence 3: CADB | Treatment Sequence 4: DCBA |
|---|---|---|---|---|
| STARTED | 8 | 8 | 8 | 8 |
| Received at Least One Dose of Study Drug | 8 | 8 | 8 | 8 |
| COMPLETED | 8 | 8 | 8 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least one dose of selpercatinib or moxifloxacin with measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTc value.
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: All randomized participants.
| Characteristic | Unit | Treatment Sequence 1: ABCD | Treatment Sequence 2: BDAC | Treatment Sequence 3: CADB | Treatment Sequence 4: DCBA | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 8 | 8 | 8 | 8 | 32 | |
| Age, Continuous | years | 35.0 (SD 11.44) | 40.3 (SD 8.78) | 44.0 (SD 8.88) | 10.18 (SD 10.18) | 40.5 (SD 10.02) |
| Sex: Female, Male: Female | Participants | 7 | 8 | 6 | 5 | 26 |
| Sex: Female, Male: Male | Participants | 1 | 0 | 2 | 3 | 6 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 4 | 4 | 4 | 14 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 | 4 | 4 | 4 | 18 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 0 | 0 | 1 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 | 0 | 4 |
| Race (NIH/OMB): White | Participants | 5 | 6 | 6 | 8 | 25 |
| Race (NIH/OMB): More than one race | Participants | 1 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: United States | Participants | 8 | 8 | 8 | 8 | 32 |
6. Primary Endpoint
The registry lists the primary outcome as Cardiodynamics: Placebo-corrected Change From Baseline in QT Interval Corrected Using Fridericia's Correction (QTcF) (ΔΔQTcF) for Treatments A, B, and C, measured over Pre-dose, -0.25, -0.5, -0.25, 0.25, 0.5, 0.75, 1.5, 2, 2.5, 3, 4, 7, 9, 12, and 24 hours post-dose.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 90% Confidence Interval |
| Unit | milliseconds |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was placebo-corrected change from baseline in the QT interval corrected using Fridericia’s correction, denoted QTcF. The QT interval is the time from the electrocardiogram Q wave to the end of the T wave and corresponds to electrical systole. Because the QT interval varies with heart rate, a correction is used to make measurements more interpretable across heart rates. QTcF is the correction method specified in the registry record.
Change from baseline describes how the measurement after dosing differs from the pre-dose reference for the relevant treatment. Placebo correction then accounts for the change observed under the matching placebo condition. In general, placebo correction helps distinguish a treatment-associated shift from changes that can occur over time or under study conditions alone. The endpoint is therefore a model-based comparison of electrocardiographic measurements, rather than a count of symptoms or clinical events.
ECGs were extracted from continuous 12-lead recordings at the specified measurement times. Participants rested supine before and after each time point’s ECG extraction. The registry reports least-squares means and 90% confidence intervals. It does not report a single summary across all post-dose times; the stated primary endpoint concerns the specified measurement schedule.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports placebo-corrected least-squares mean QTcF changes of 3.4 milliseconds for 320 mg selpercatinib, with a 90% confidence interval from 0.4 to 6.34; 4.4 milliseconds for 640 mg selpercatinib, with a 90% confidence interval from 1.37 to 7.4; and 6.4 milliseconds for 400 mg moxifloxacin, with a 90% confidence interval from 3.38 to 9.43. These are the posted estimates for Treatments A, B, and C, respectively.
A least-squares mean is a model-based estimate, rather than necessarily a simple arithmetic average of the observed measurements. The confidence interval describes uncertainty around the estimated mean under the analysis used. In general, a wider interval indicates less precision, while a narrower interval indicates greater precision. The registry gives 90% confidence intervals, but does not provide the underlying model specification or enough detail to independently assess how the intervals were constructed.
The estimates are presented separately for each treatment, and the registry record does not provide a formal pairwise comparison between the selpercatinib doses and placebo or between selpercatinib and moxifloxacin. It also does not report p-values for these results. The estimates and their intervals therefore should not be treated as a reported test of whether treatments differ from one another. Comparisons based only on the displayed point estimates would not account for the crossover structure, correlation between measurements, or the full analysis model.
Moxifloxacin is identified as the positive control. In general, a positive control can help assess whether a study’s measurement approach can detect a known response pattern. The registry record reports its QTcF estimate and interval but does not state an assay-sensitivity criterion or report a formal assessment against such a criterion. The positive-control result should therefore be read as part of the study design and as a posted estimate, not as proof of a particular methodological conclusion.
The population was healthy participants, and the endpoint was a measured QTcF change over the specified post-dose schedule. These results do not establish effects in other populations, over other durations, or on clinical events. The registry lists 8 for each treatment estimate. The meaning of those reported treatment-specific counts should be interpreted within the crossover design rather than by summing across treatments.
9. Statistical Methods Explained
The registry identifies the primary estimate as a least-squares mean and its dispersion as a 90% confidence interval. These terms describe different parts of the result: the least-squares mean is the estimated treatment-related outcome from a statistical model, while the interval conveys uncertainty around that estimate. General statistical interpretation: a confidence interval is not a range containing every participant’s response. It concerns uncertainty in an estimated quantity under the assumptions of the analysis.
What does placebo correction represent?
The endpoint is a placebo-corrected change from baseline. First, change from baseline compares a post-dose QTcF measurement with the corresponding pre-dose baseline. Placebo correction then contrasts the treatment-related change with the change under selpercatinib-matching placebo. This approach is intended to distinguish a treatment-associated difference from changes also observed during the placebo condition. The registry describes the endpoint as based on a model-predicted effect, but does not report the detailed model or its covariates.
Why use a crossover design?
In a crossover trial, participants receive treatments in different periods and in randomized sequences. General statistical explanation: because treatment conditions are assessed within a treatment sequence, analyses may need to account for repeated measurements from the same participant and for period or sequence effects. Measurements from the same participant are generally related, so treating all observations as independent can misstate uncertainty. The registry describes a randomized, double-blind, four-way crossover and lists four treatment sequences. It does not report the statistical method used to account for within-participant correlation, period effects, sequence effects, or possible carryover.
Crossovers can make within-participant comparisons informative when the design and analysis appropriately address these features. They also depend on having usable observations across the relevant periods. The registry’s primary population definition requires baseline data and at least one valid post-dose change measurement after at least one dose of selpercatinib or moxifloxacin. That definition does not, by itself, explain how incomplete treatment-period data were handled in the model.
What does the confidence interval say?
The 90% confidence intervals accompany the least-squares mean estimates in milliseconds. General statistical explanation: an interval reflects both the estimated effect and its precision under the model; it is not a guarantee that the true effect lies within the particular interval. Its interpretation depends on the design, data, and analysis assumptions. The registry record does not report a confidence-interval procedure, degrees of freedom, model diagnostics, or sensitivity analyses, so the posted intervals cannot be independently reconstructed from the record.
The intervals are not individual-level ranges, and they do not directly describe how much QTcF changed for every participant. Nor do separate confidence intervals constitute a formal comparison between treatments. A direct treatment contrast would require an estimated difference and its uncertainty from the analysis. Such pairwise estimates are not reported in the registry record.
How should the positive control be understood?
Moxifloxacin was included as a positive control, and the registry reports its treatment-specific least-squares mean and interval. In general, positive controls are used to evaluate whether a study’s procedures can detect an expected measurement response. That role depends on prespecified criteria and an appropriate analysis. The registry record does not report those criteria or a formal assay-sensitivity analysis. It is therefore possible to describe the posted moxifloxacin estimate, but not to claim a registry-reported validation conclusion.
The record also describes ECG extraction from continuous 12-lead recordings at pre-specified time points and rest before and after extraction. Repeated measurements across time can be informative about the pattern of response, but the primary estimate details do not provide a complete time-course interpretation. The registry does not report the model’s handling of measurements across the specified times or a single time-point result in the analyzed primary summary.
The posted results list no analysis entries, and the registry record does not report the full statistical analysis plan. Consequently, the exact model form, treatment contrasts, handling of missing observations, multiplicity approach, and assumptions used for inference are not available in the registry record. The least-squares means and confidence intervals should be understood as the reported summaries, with those analysis details unresolved.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint includes QTcF assessments at pre-dose and multiple specified post-dose times, while estimates are reported for Treatments A, B, and C. Examining multiple treatments or time points can raise a multiplicity question: when many statistical comparisons are made, the chance of at least one apparently notable result can increase. General statistical methods can address this through prespecified testing sequences or adjustment procedures. The registry record does not report a multiplicity strategy, a hierarchy of tests, or p-values for the primary outcome.
The registry lists 8 outcome measures and 0 secondary outcomes posted. It also lists 0 analysis entries. These registry counts do not establish whether additional analyses were conducted; the statistical analysis plan and any unposted analyses are not reported in the registry record. No sample-size justification is reported. A separate planning illustration may use stated assumptions, but such planning values are not observed power and do not describe the trial’s actual design justification.
The primary population definition requires baseline data and at least one valid post-dose change measurement after at least one dose of selpercatinib or moxifloxacin. This indicates which participants qualified for that endpoint population, but the record does not provide a missing-data breakdown or explain how missing measurements were handled. It also does not describe imputation, sensitivity analyses, or reasons for missing observations. The reported treatment-specific counts should not be interpreted as proof that all scheduled observations were complete.
Because the study used a crossover design, incomplete measurements in one period could affect the available within-participant information. The registry record does not explain whether all treatment periods were required for inclusion in the primary analysis or how partially observed sequences were incorporated. These omissions limit assessment of the analysis population and the robustness of the reported estimates.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 320 mg Selpercatinib | 0 | 32 | 0.0% |
| 640 mg Selpercatinib | 0 | 32 | 0.0% |
| 400 mg Moxifloxacin | 0 | 32 | 0.0% |
| Selpercatinib Matching Placebo | 0 | 32 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 320 mg Selpercatinib | 0 of 32 |
| 640 mg Selpercatinib | 0 of 32 |
| 400 mg Moxifloxacin | 0 of 32 |
| Selpercatinib Matching Placebo | 0 of 32 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 320 mg Selpercatinib | 6 of 32 |
| 640 mg Selpercatinib | 2 of 32 |
| 400 mg Moxifloxacin | 0 of 32 |
| Selpercatinib Matching Placebo | 4 of 32 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 320 mg Selpercatinib | 640 mg Selpercatinib | 400 mg Moxifloxacin | Selpercatinib Matching Placebo |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | 2 of 32 | 0 of 32 | 0 of 32 | 4 of 32 |
| Nausea | Gastrointestinal disorders | 2 of 32 | 0 of 32 | 0 of 32 | 0 of 32 |
| Vessel puncture site pain | General disorders | 0 of 32 | 2 of 32 | 0 of 32 | 0 of 32 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 2 of 32 | 0 of 32 | 0 of 32 | 0 of 32 |
The registry reports serious adverse events affecting 0 participants in each of the four treatment groups: 320 mg selpercatinib, 640 mg selpercatinib, 400 mg moxifloxacin, and selpercatinib-matching placebo. Each group lists 32 at risk for serious adverse events. The registry also reports 0 deaths in each group and lists no serious adverse event terms.
For other adverse events, the record reports 6 affected in the 320 mg selpercatinib group, 2 in the 640 mg selpercatinib group, 0 in the moxifloxacin group, and 4 in the matching placebo group; each group lists 32 at risk. These are group-specific registry counts. Because the study was a crossover, the group counts should not be added to infer a number of distinct participants.
These figures describe the adverse-event entries in the registry record. They do not provide event timing, duration, severity for the non-serious events, or a detailed account of the event terms. The record does not report additional detail needed to compare event profiles or attribute an event to a particular exposure. The absence of reported serious events is a description of these posted counts, not a conclusion about safety beyond this study and its recorded observations.
12. What the Result Does, and Does Not, Mean
The posted primary results quantify placebo-corrected QTcF changes for the two selpercatinib treatments and the moxifloxacin positive control. The estimates are least-squares means in milliseconds with 90% confidence intervals. They provide a summary of the modeled endpoint in the registry’s defined analysis population under the study conditions.
These results do not, by themselves, establish a formal difference between the selpercatinib treatments, placebo, or moxifloxacin. The registry record does not report the pairwise contrasts, p-values, or a prespecified decision criterion needed to interpret a formal treatment comparison. A treatment’s point estimate should not be read as the response of every participant, and the confidence interval is not an individual response range.
The study addressed an electrocardiographic measurement in healthy participants after specified treatments and at specified time points. It did not report clinical outcomes, and the registry record does not describe results in people with a medical condition. Its findings therefore should not be extended to other populations, longer exposure, other dosing conditions, or outcomes not measured in this study.
The presence of moxifloxacin as a positive control is relevant to the design, but the record does not report a formal assay-sensitivity conclusion or criterion. Likewise, no conclusion about the adequacy of the statistical model can be drawn from the estimates alone because the model specification and analysis plan are not reported. The posted results are best read as estimates with stated uncertainty, alongside the limitations in the record, rather than as a complete account of all inferential analyses.
13. Why This Trial Matters Statistically
This trial illustrates how a crossover design can be used to study a short-term measurement under multiple treatment conditions. Randomized treatment sequences and blinding are important design features, while the model-based least-squares means provide estimates for the primary endpoint. Understanding the design matters because observations across treatment periods are connected within participants; a simple comparison that ignores that structure may not reflect the intended analysis.
The endpoint also demonstrates the distinction between a raw measurement and a corrected, placebo-referenced outcome. QTcF adjusts the QT interval for heart rate, and the placebo correction references change under matching placebo. These steps define what the reported estimate represents. Readers should distinguish the resulting model-based estimate from an unadjusted change, an individual response, or a clinical event.
The study includes a positive control, which has a methodological role in evaluating measurement performance in general. However, a control group’s presence is not the same as a reported formal assay-sensitivity result. That distinction is especially important when the registry record does not report the criteria or analysis used for such a conclusion.
Finally, the record shows why registry summaries need to be read with attention to reporting completeness. Estimates and confidence intervals are available, but detailed model specification, multiplicity procedures, missing-data handling, and pairwise contrasts are not reported in the registry record. Statistical interpretation depends not only on the numerical estimates but also on the design and the analysis choices that connect observations to those estimates.
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 does not report the full statistical analysis plan, detailed model specification, or the method used to construct the confidence intervals. It also does not report formal pairwise comparisons or p-values. Consequently, the reported least-squares means cannot be used to establish a registry-reported inferential contrast between treatments.
The primary endpoint was measured at pre-dose and specified post-dose times, but the record does not explain how the repeated measurements over time were modeled or whether a single time point was designated for a treatment comparison. The record also does not report a multiplicity procedure for the multiple treatments and time points. These gaps make it difficult to assess the intended control of statistical error across possible comparisons.
The population definition permits inclusion with at least one valid post-dose change measurement after at least one dose of selpercatinib or moxifloxacin. The registry does not report completeness by period, reasons for missing measurements, or how incomplete crossover sequences were treated. Period, sequence, and carryover handling are also not reported, although they are relevant considerations for crossover analyses.
The study enrolled healthy participants and assessed an ECG endpoint over a defined post-dose schedule. The registry record does not report clinical outcomes or results for other populations. The posted results therefore have a narrow scope, and the record lacks detail needed to evaluate broader applicability. A sample-size justification is not reported, so the enrollment figure alone does not explain the study’s intended precision or power.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Effect of Selpercatinib (LY3527723) on Corrected QT (QTc) Interval in Healthy Participants — NCT05630274.
- Registry record last updated 2025-09-18; status last verified 2025-08.
- Results first posted 2025-09-18.
- 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.
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18. Record Summary
NCT05630274 is a completed Phase 1 randomized, double-blind, four-way crossover study in healthy adult participants. The registry lists an enrollment of 32, study start of 2019-04-16, and primary completion of 2019-06-21. Treatments included selpercatinib at 320 mg and 640 mg, matching placebo, and 400 mg moxifloxacin as a positive control.
The primary endpoint was placebo-corrected change from baseline in QTcF, reported as least-squares means with 90% confidence intervals. Treatment-specific estimates are reported for the two selpercatinib conditions and moxifloxacin. The registry also lists adverse-event counts, with 0 serious adverse events and 0 deaths in each treatment group.
The record does not report the detailed analysis plan, pairwise comparisons, multiplicity strategy, or missing-data methods. The posted estimates should therefore be interpreted as treatment-specific summaries rather than as a complete set of formal comparative analyses.