Evaluate the Effect of Atorvastatin on the Pharmacokinetics of Lomitapide in Healthy Subjects.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluate the Effect of Atorvastatin on the Pharmacokinetics of Lomitapide in Healthy Subjects. (NCT02080455), a randomized phase 1 study. The primary outcome is Cmax.

2. Clinical Question

3. Trial Design

This was a phase 1, randomized, open-label, parallel, two-arm study of atorvastatin's effect on lomitapide pharmacokinetics in healthy subjects. The registry identifies Aegerion Pharmaceuticals, Inc. as the sponsor and gives the status as completed. The recorded start date is 2014-01-27, and the primary completion date is 2014-03-07. Enrollment was 32.

The arm descriptions specify two single oral lomitapide doses of 20 mg, on Day 1 and Day 15, in both schedules. In the simultaneous schedule, participants received 11 single oral atorvastatin doses of 80 mg from Day 11 through Day 21. In the other schedule, atorvastatin was administered from Day 12 through Day 22, approximately 12 hours apart from lomitapide. The primary outcome description, however, identifies the coadministration results as simultaneous. The record does not make clear how the posted primary outcome values relate to the approximately 12-hour schedule.

Randomization can help balance characteristics between groups, while an open-label design means masking was not used. This study is focused on pharmacokinetic measurements rather than a clinical outcome. The registry defines the PK Population as participants who received at least one dose of study drug and had evaluable PK data. It reports 16 participants for each of the displayed lomitapide-alone and simultaneous-coadministration outcome groups. Further details of the randomization procedure and any protocol-specific design rationale 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

Analysis population for the primary outcome, as defined in the registry: The PK Population consisted of all subjects who received at least one dose of study drug and have evaluable PK data.

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 Cmax, measured over Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing.

The primary endpoint is Cmax: the maximum observed concentration of lomitapide and its two primary metabolites, M1 and M3, in plasma after dosing. The registry specifies predose measurement and sampling at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing. Concentration is reported in ng/mL, with geometric means and geometric coefficients of variation.

Cmax is used in pharmacokinetic research to describe the highest measured plasma concentration during the sampling period. It captures a different feature of drug exposure from measures that account for exposure over time, such as AUC, or the time at which the peak occurs, Tmax. The registry lists AUC0-t, AUC0-∞, Tmax, and t1/2 among secondary outcomes, but the primary endpoint is the maximum observed concentration.

Because Cmax depends on the sampling schedule, the reported maximum is the highest observed value among the scheduled measurements, not necessarily a continuously observed biological peak. The record gives summary values for the parent drug and metabolites, but does not report confidence intervals or a formal comparison for these Cmax results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Pharmacokinetic summaries describe how measured drug concentrations behave over time. Here the primary measure is Cmax, the highest observed plasma concentration for lomitapide and metabolites M1 and M3. The registry reports geometric means and geometric coefficients of variation, rather than arithmetic means and standard deviations. The posted values are descriptive summaries, and no comparative analysis is listed.

What does a geometric mean describe?

General: A geometric mean is a measure of central tendency suited to positive measurements that may vary multiplicatively. It is calculated on a logarithmic scale and then expressed back on the original scale. It can be useful for pharmacokinetic data, where individual concentrations may be unevenly distributed. It should not be interpreted as the concentration of every participant or as an estimate of the treatment contrast on its own.

The reported geometric means are 0.94 ng/mL and 2.0 ng/mL for lomitapide alone and simultaneous coadministration, respectively. For M1, the corresponding values are 2.24 ng/mL and 2.11 ng/mL; for M3, they are 32.3 ng/mL and 27.2 ng/mL. Those values summarize each group separately. A direct inferential comparison would require an estimate of the contrast and its uncertainty, neither of which is reported in the registry record.

How should the variability measure be read?

The registry reports geometric coefficients of variation alongside the geometric means. These describe relative variability among measured values within a group. For lomitapide, the reported values are 34.5 with lomitapide alone and 52.9 with simultaneous coadministration. For M1, they are 22.8 and 31.9; for M3, they are 40.6 and 62.0. A coefficient of variation is not a confidence interval and does not directly quantify uncertainty in the difference between group means.

General: Over-dispersion means that observations vary more than a statistical model expects. When variability is substantial, estimates can be less precise and model assumptions matter. A dispersion summary can alert readers to variation in the observations, but the registry's descriptive coefficient alone does not establish that a particular model was used or that over-dispersion was formally assessed. The statistical model and any diagnostics are not reported in the registry record.

Why do confidence intervals matter?

General: A confidence interval expresses uncertainty around an estimated quantity under a specified statistical method. For a group contrast, it helps readers assess both the plausible range of the contrast and its precision. A point estimate without an interval gives less information about uncertainty. In these posted Cmax results, confidence limits are not reported, and the registry lists no analyses. It is therefore not possible to describe the precision of a formal treatment contrast from the posted summaries alone.

A p-value would answer a different, limited question under a specified testing framework. It would not measure the size or practical importance of an effect. No p-value or testing procedure for the primary Cmax comparison is reported in the registry record. The absence of a posted test should not be replaced with an assumption about what the protocol or sponsor analysis may have planned.

What does the analysis population mean?

The registry defines the PK Population as all subjects who received at least one dose of study drug and had evaluable PK data. That definition indicates that inclusion in the pharmacokinetic summaries depends on both exposure to study drug and availability of evaluable PK measurements. Each reported outcome group has 16 participants. The record does not report how many participants, if any, were excluded from the PK Population, the reasons for unevaluable data, or how missing measurements were handled.

General: Analysis-population definitions affect interpretation because they clarify who contributes to an estimate. A population restricted to evaluable measurements may differ from everyone randomized if any data are unavailable or excluded. The registry definition is clear, but the record does not provide a participant flow or further details to determine whether the reported population differs from the randomized groups.

Sample-size calculations based on an observed effect are planning illustrations, not evidence of the study's original design justification and not observed power. The assumptions described for such illustrations include a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect expressed as a fraction of the observed effect. The trial's own sample-size justification is not reported in the registry record. No planning sample-size result is stated in the registry entries for interpretation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists Cmax as the primary outcome and names Tmax, AUC0-t, AUC0-∞, and t1/2 among secondary outcomes. It reports 10 outcome measures and five posted secondary outcomes. Multiple outcomes can raise multiplicity questions because testing many hypotheses may increase the chance of at least one apparently notable result. The registry record does not report whether any multiplicity adjustment was planned or applied. Because no analyses or p-values are listed, the posted results do not permit assessment of how multiplicity was handled in inferential testing.

The PK Population includes participants who received at least one dose and had evaluable PK data. The record does not report missing-data counts, reasons for missingness, imputation, or sensitivity analyses. It also does not report a participant flow explaining whether all randomized participants contributed to each outcome. The reported group sizes are 16 for each displayed Cmax group, but these summaries alone do not establish whether every scheduled sample was available for every participant.

These details matter because missing measurements can affect which observations contribute to pharmacokinetic summaries, and multiplicity decisions affect interpretation when several outcomes are assessed. Neither the handling of missing data nor the statistical approach to multiple outcomes is reported in the registry record. No assumptions about those procedures can be drawn from the outcome values alone.

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 registry reports serious adverse events for two groups of 16 participants: the schedule described as lomitapide and atorvastatin taken together, and the schedule described as approximately 12 hours between administration. There were zero participants with serious adverse events in each group, and zero deaths in each group.

For the registry's other-event category, 12 participants in the taken-together group and five participants in the approximately 12-hour group were reported as affected. These are participant counts, not a count of all events; the registry figures do not indicate whether an affected participant had more than one event. No serious adverse-event terms are listed.

Zero reported serious events in these groups describes what was recorded in this study; it does not establish that an event is impossible or characterize risk beyond the observed participants and study conditions. The record does not provide further detail in the listed safety summaries about event types, severity, relatedness, or timing. The group schedules differ, and the safety counts should be read as descriptive rather than as a formal comparison.

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

The posted primary outcome values describe geometric mean maximum plasma concentrations for lomitapide, M1, and M3 in the reported lomitapide-alone and simultaneous-coadministration groups. The lomitapide geometric mean is higher with simultaneous coadministration, while the M1 and M3 geometric means are lower. The accompanying geometric coefficients of variation indicate that individual measurements varied within each group. These statements describe the posted summaries and do not establish the precision or statistical significance of a group contrast.

The study addresses a pharmacokinetic question in healthy subjects, not a clinical-outcome question. Cmax is one aspect of drug exposure; the registry also names other pharmacokinetic measures as secondary outcomes. The posted summary values alone do not describe all aspects of exposure or establish what the concentrations imply for people outside the studied population.

No confidence intervals, p-values, or formal comparative analyses are reported for the Cmax results. The record also does not report the statistical plan, missing-data handling, multiplicity approach, or sample-size justification. As a result, readers cannot use the posted figures to judge the uncertainty of an inferential contrast or to reconstruct the sponsor's intended analysis.

The arm descriptions include an approximately 12-hour timing schedule, but the posted primary outcome values identify the coadministration group as simultaneous. The record does not identify corresponding primary Cmax values for the approximately 12-hour schedule. Accordingly, the displayed summaries should not be taken as a full numerical comparison between both atorvastatin timing schedules.

The safety counts are also descriptive. The record reports zero serious adverse events and zero deaths in each of the two safety groups, as well as participants affected in the other-event category. These observations do not establish outcomes beyond the participants and study conditions recorded.

13. Why This Trial Matters Statistically

This trial illustrates why pharmacokinetic results should be read as more than a comparison of group averages. Cmax captures the highest observed plasma concentration during a specified sampling schedule, while geometric coefficients of variation convey relative variability among the measured values. In this record, the reported group summaries point in different directions for the parent drug and its two metabolites. Interpretation therefore depends on distinguishing each analyte and avoiding a single generalized statement about all pharmacokinetic results.

It also shows the importance of identifying precisely which regimen a result represents. The arm descriptions include simultaneous administration and an approximately 12-hour separation schedule, but the primary outcome description and posted values identify lomitapide alone and simultaneous coadministration. The registry does not identify a corresponding primary outcome summary for the other timing schedule. Clear links between an arm, its dosing schedule, and its outcome estimate are necessary for a meaningful comparison.

Finally, descriptive estimates are not substitutes for comparative inference. The posted means and variability measures do not include confidence intervals or a formal statistical test. Without those, readers can describe the observed summaries but cannot judge the precision of a treatment contrast from the registry record. The study also demonstrates that a registry's population definition and missing-data details matter: the PK Population requires evaluable data, while the record does not explain whether measurements were missing or excluded.

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 primary limitation for interpreting the pharmacokinetic comparison is the absence of reported inferential results. The registry gives geometric means and geometric coefficients of variation but no confidence intervals, p-values, or comparative estimates. It also lists zero analyses. The size and precision of a formal contrast therefore cannot be established from the posted results.

The primary outcome description specifies simultaneous coadministration, while the arm descriptions also include an approximately 12-hour schedule. The posted outcome values distinguish lomitapide alone from simultaneous coadministration; no corresponding primary Cmax values are identified for the approximately 12-hour schedule. This limits interpretation of the full timing comparison described in the trial arms.

The record defines the PK Population by receipt of at least one dose and evaluable PK data, but does not report missing measurements, exclusions, reasons data were unevaluable, or sensitivity analyses. It lists secondary pharmacokinetic outcomes but does not report a multiplicity approach. Further details of the analysis plan, sample-size rationale, randomization procedure, and statistical model are not reported in the registry record.

The study enrolled healthy subjects, and the posted endpoint concerns plasma concentrations rather than clinical outcomes. The registry summaries therefore have a specific population and measurement scope. Safety information is limited to the listed group counts and does not include further details about event characteristics in the posted record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluate the Effect of Atorvastatin on the Pharmacokinetics of Lomitapide in Healthy Subjects. — NCT02080455.
• Registry record last updated 2020-03-10; status last verified 2020-02.
• Results first posted 2020-03-10.
• 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

NCT02080455 is a completed phase 1 randomized, open-label, parallel, two-arm study sponsored by Aegerion Pharmaceuticals, Inc. It enrolled 32 healthy subjects to examine the effect of atorvastatin on lomitapide pharmacokinetics. The registry records a start date of 2014-01-27 and a primary completion date of 2014-03-07.

The primary outcome is Cmax for lomitapide and metabolites M1 and M3. The posted results report geometric means and geometric coefficients of variation for lomitapide alone and simultaneous coadministration, with 16 participants in each displayed group. No comparative analysis or confidence interval is reported. Safety summaries report zero serious adverse events and zero deaths in each group, with other-event category counts of 12 and five participants affected.

The registry also describes an approximately 12-hour dosing schedule, but the corresponding primary Cmax values are not identified in the posted results. Statistical-plan details and missing-data handling are not reported in the registry record.