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 Study to Determine the Intra-subject Variability of Pharmacokinetics of Lomitapide in Healthy Subjects (NCT01915771), a na phase 1 study. The primary outcome is Cmax.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01915771 |
| Phase | Phase 1 |
| Condition | Intra-subject Variability of Pharmacokinetics |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Aegerion Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Healthy subjects enrolled in a Phase 1 pharmacokinetic study. The registry record lists enrollment of 15; the primary pharmacokinetic analysis of lomitapide included 13 subjects with evaluable data in both study periods.
Intervention
Two single oral doses of 20 mg lomitapide, with at least a 14-day washout between doses. The study was open-label.
Comparator
The study did not use a separate control group. Its crossover structure allowed repeat dosing within participants; the registry record describes a single-group study and does not report a randomized comparison.
Primary question
How variable is the pharmacokinetics of lomitapide within the same subject across the two study periods? The primary endpoint is Cmax, the maximum observed concentration of lomitapide and its metabolites M1 and M3. The numerical results addressing that question are not reported in the registry record.
This is a pharmacokinetic question about measured drug concentrations, not a comparison of clinical outcomes between treatment groups. In general, repeated measurements in the same person can help describe within-subject variation while limiting the influence of stable differences between people. The record does not specify the statistical method used to quantify that variation or provide a numerical estimate.
3. Trial Design
The study is registered as a Phase 1, open-label, crossover study with a single-group model. It enrolled 15 healthy subjects. The intervention description specifies two single oral doses of 20 mg lomitapide, separated by at least a 14-day washout. The study is listed as completed; its recorded start date is 2013-07-29 and its primary completion date is 2013-08-23.
There was no separate control arm and no randomized allocation is reported. The two study periods therefore represent repeated dosing in a single-group design, rather than a parallel comparison between treatment and control groups. The registry record does not report the sequence assignment process or additional details about the crossover procedure beyond the dose and washout description.
The primary endpoint is Cmax, described as the maximum observed concentration of lomitapide and its metabolites M1 and M3. Concentration sampling is listed as pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose. The primary outcome is a continuous measure, with mean and standard deviation identified as its summary format.
For lomitapide, 13 subjects with evaluable pharmacokinetic data in both study periods were included in the primary pharmacokinetic analysis. The record describes exclusions from the M1 and M3 analyses in each period, but the reason for one of those exclusions is incomplete in the registry record. Although six outcome measures are listed, the record lists no analyses. It does not report a statistical analysis plan or explain how the within-subject variability estimate was derived.
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.
Day 1
| Stage | Lomitapide |
|---|---|
| STARTED | 15 |
| COMPLETED | 14 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Lomitapide |
|---|---|
| Withdrawal by Subject | 1 |
Day 15
| Stage | Lomitapide |
|---|---|
| STARTED | 14 |
| COMPLETED | 13 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Lomitapide |
|---|---|
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: Only 13 subjects who had evaluable PK data in both study periods were included in the PK analysis of lomitapide. One subject was excluded from PK analysis of M1 and M3 during Period 1 due to early termination. Another subject was excluded from PK analysis of M1 and M3 during Period 2 because the subject did not complete both Periods 1 and 2.
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.
| Characteristic | Unit | Lomitapide |
|---|---|---|
| Participants analysed | 15 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 15 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 26.2 (SD 4.9) |
| Sex: Female, Male: Female | Participants | 6 |
| Sex: Female, Male: Male | Participants | 9 |
| Region of Enrollment: United Kingdom | participants | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Cmax, measured over Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | ng/mL |
| Endpoint classification | Continuous Endpoint |
Cmax is the maximum observed concentration of a drug in the sampling period. In this study, the registry describes the endpoint as the maximum observed concentration of lomitapide and its metabolites M1 and M3. Concentrations were sampled from pre dose through 168 hours post dose, at the times listed in the trial design.
In general, Cmax is used to describe peak measured exposure. It is distinct from a measure that summarizes concentration over the full sampling period: Cmax focuses on the highest observed value. Repeated Cmax measurements after doses in the same person can be used to examine how much peak exposure varies within that person. That is the stated pharmacokinetic focus of this study.
The registry identifies the outcome as continuous and specifies a mean and standard deviation as summary statistics. These summaries describe the distribution of measured values, but a mean and standard deviation alone do not necessarily quantify within-subject variability. That requires a method that accounts for repeated observations from the same participant. The method used for that purpose is not reported in the registry record. Numerical Cmax estimates and their dispersion are also not reported in the registry record, so the magnitude and precision of the observed variability cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study addresses repeatability of pharmacokinetic measurements within participants after two single oral doses of 20 mg lomitapide. The design is relevant to that question because it includes repeated dosing in a crossover structure rather than assigning participants to separate parallel groups. However, the record does not provide the numerical Cmax results needed to describe the observed degree of within-subject variation.
For lomitapide, 13 subjects with evaluable pharmacokinetic data in both study periods were included in the analysis. This is the analysis population described for the primary pharmacokinetic analysis, while the overall enrollment was 15. The record also describes exclusions from M1 and M3 analyses: one subject was excluded in Period 1 due to early termination, and another was excluded in Period 2. The explanation for the latter exclusion is incomplete in the registry record. These details matter because the analyzable set differs by analyte and study period.
The endpoint summary format is a mean and standard deviation. In general, the mean describes a central value and the standard deviation describes spread around that value. For repeated measurements, though, a standard deviation calculated without accounting for the pairing may combine within-subject and between-subject variation. The registry record does not state which calculation was used to isolate within-subject variability, nor does it give a numerical estimate or confidence interval.
The record does not report an inferential test, a p-value, a confidence interval, or a prespecified threshold for interpreting variability. It therefore does not support a conclusion about the precision of the estimate or whether the observed variation met any criterion. The listing of six outcome measures does not establish which were analyzed or how their results were interpreted; the registry record lists no analyses.
Adverse-event counts are recorded separately by period. Serious events were reported for zero of 15 participants at risk in Period 1 and zero of 13 at risk in Period 2. The counts for other events were four of 15 and one of 13, respectively; deaths were zero in both periods. These period-specific entries should not be treated as a direct randomized comparison. The study was not a randomized comparison, the participant counts differ by period, and the record does not explain whether the same individuals contributed across periods.
Overall, the registry describes the question, design, endpoint, and analysis population, but not the numerical pharmacokinetic findings. Without those estimates and a description of their calculation, the degree of variability and its statistical precision are not reported in the registry record.
9. Statistical Methods Explained
The registered outcome is continuous, and its stated summary format is mean and standard deviation. In general, the mean is a measure of the center of a set of observations. The standard deviation describes how spread out observations are around that center. Neither summary, by itself, explains how observations from the same participant were handled in a repeated-dose study.
In general, within-subject variability concerns changes in measurements within an individual across repeated conditions or occasions. Between-subject variability concerns differences from one individual to another. When observations are paired by participant, a method that preserves that pairing can distinguish the within-person component from differences among participants. Treating paired values as if they came from unrelated people can answer a different question and may give an inappropriate measure of uncertainty. The registry record does not identify the calculation or model used to estimate within-subject variability.
A crossover structure can support within-person comparisons because each participant may contribute measurements under more than one study period. This can reduce the influence of stable participant characteristics on a comparison of repeated measurements. That is a general property of crossover designs, not a reported result about this study. The record says there were two single oral doses with at least a 14-day washout between doses, but it does not report sequence assignment, period effects, carryover assessment, or the assumptions used in analysis.
The endpoint is Cmax, defined in the record as the maximum observed concentration of lomitapide and its metabolites M1 and M3. In general, a maximum observed concentration depends on the sampling schedule: the measured peak is the highest value among the collected samples, and a peak between sampling times may not be directly observed. The registry lists sampling from pre dose through 168 hours post dose, with multiple post-dose time points. It does not report whether the concentration-time data were complete for every participant or how missing samples, if any, were handled.
A confidence interval, in general, describes a range of values compatible with the data under a specified statistical procedure. Its width reflects uncertainty as well as the scale of the estimate. The registry record does not report a confidence interval for Cmax or for within-subject variability. Without an interval or another uncertainty measure, the precision of any estimated variability cannot be evaluated from the record. No p-value or hypothesis test for the primary endpoint is reported either.
In general, over-dispersion means that observed variation is greater than a chosen model or distribution would expect. When present, a model that assumes too little variation can understate uncertainty. Repeated pharmacokinetic measurements may have more complex variation than a simple summary captures, but the registry record does not report whether over-dispersion was assessed or whether any particular distributional model was used. This is a general statistical consideration, not a finding about this trial.
Analysis populations also require clear definitions. In general, a complete-case or evaluable-data analysis includes participants with the measurements needed for a specified calculation; its results may differ from analyses that use a broader population or handle missing measurements under explicit assumptions. Here, the registry identifies 13 subjects with evaluable pharmacokinetic data in both periods for the lomitapide analysis, out of 15 enrolled. It describes exclusions for M1 and M3 by period, including one due to early termination and another with an incomplete explanation. The record does not define a broader intention-to-treat population or explain any missing-data method.
The registry lists six outcome measures and no analyses. This does not establish that no statistical work was performed; it means the registry record does not list the analyses. It also does not state whether a protocol or analysis plan specified the estimator, handling of period or sequence effects, treatment of incomplete profiles, or inferential procedures. Those details cannot be inferred from the design label or from the summary-statistic format.
Multiplicity is a general concern when several endpoints or comparisons are tested: repeated testing can increase the chance of at least one apparently noteworthy result. The record lists six outcomes but does not report a multiplicity strategy or identify a hierarchy of tests. Since numerical results and analyses are not reported in the registry record, there is no basis to assess whether or how multiplicity affected interpretation.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists six outcome measures but no analyses. It identifies Cmax as the primary endpoint, while the statistical testing procedures and the relationship among the listed outcomes are not reported. The record does not describe a prespecified hierarchy, adjustment for multiple testing, or another multiplicity strategy. In general, when multiple outcomes are examined, multiplicity procedures can help control the chance of a false-positive finding across tests. Whether such procedures were used in this study is not reported in the registry record.
The record identifies 15 enrolled subjects and states that 13 subjects with evaluable pharmacokinetic data in both periods were included in the lomitapide analysis. It also notes exclusions from the M1 and M3 analyses by period. One exclusion was due to early termination; the explanation for the other is incomplete in the registry record. The record does not describe a general missing-data method, imputation, or sensitivity analysis.
In general, excluding participants or measurements with incomplete data can affect which population an estimate represents. If incompleteness is related to the measured outcome, an analysis limited to evaluable data may not represent all enrolled participants. That is a general limitation to consider, not evidence that the exclusions in this study were related to Cmax. The registry record does not explain the causes of missing pharmacokinetic measurements beyond the stated early termination, or whether missingness was assessed.
The analysis population is therefore clear only for lomitapide: 13 subjects with data evaluable in both periods. A separate population definition for every outcome and analyte is not fully available in the record. The statistical analysis plan, the handling of multiple outcomes, and methods for incomplete data are not reported in the registry record.
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 |
|---|---|---|---|
| Period 1 | 0 | 15 | 0.0% |
| Period 2 | 0 | 13 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Period 1 | 0 of 15 |
| Period 2 | 0 of 13 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Period 1 | 4 of 15 |
| Period 2 | 1 of 13 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Period 1 | Period 2 |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 3 of 15 | 0 of 13 |
| Abdominal Discomfort | Gastrointestinal disorders | 2 of 15 | 1 of 13 |
| Nausea | Gastrointestinal disorders | 2 of 15 | 0 of 13 |
| Abdominal Pain | Gastrointestinal disorders | 1 of 15 | 0 of 13 |
| Flatulence | Gastrointestinal disorders | 1 of 15 | 0 of 13 |
| Headache | Nervous system disorders | 0 of 15 | 1 of 13 |
| Lymphdenopathy | Blood and lymphatic system disorders | 1 of 15 | 0 of 13 |
| Upper Respiratory Tract Infection | Infections and infestations | 1 of 15 | 0 of 13 |
| Back Pain | Musculoskeletal and connective tissue disorders | 1 of 15 | 0 of 13 |
| Anxiety | Psychiatric disorders | 1 of 15 | 0 of 13 |
The adverse-event entries are reported by study period. In Period 1, zero of 15 participants at risk had a serious event, four of 15 had an event in the other-event category, and deaths were zero. In Period 2, zero of 13 participants at risk had a serious event, one of 13 had an event in the other-event category, and deaths were zero.
These are counts for each period, not a randomized comparison between groups. The study used a single-group crossover design, and the record does not clarify whether the same participants contributed to both period counts. The denominators also differ. The counts should therefore be read as period-specific registry entries, not added together to produce a number of unique participants or interpreted as a comparative effect.
The record does not list serious-event terms. It also does not provide additional detail on the nature, timing, severity, or relationship to lomitapide of the other events. Zero serious events recorded in these entries does not by itself establish the absence of all safety concerns; it describes only the reported counts. Broader safety interpretation is limited by the information in the registry record.
12. What the Result Does, and Does Not, Mean
The study was designed to assess intra-subject variability in the pharmacokinetics of single oral 20 mg lomitapide doses. Its crossover structure and repeat dosing align with a within-subject pharmacokinetic question. The endpoint, Cmax, concerns peak observed concentrations of lomitapide and metabolites M1 and M3, sampled at the listed times through 168 hours after dosing.
What the record does not establish is the numerical size of the variability. It gives no Cmax mean, standard deviation, within-subject variability estimate, confidence interval, or inferential result. Thus, it is not possible from the registry record to describe how similar or different the measured concentrations were between study periods or how precisely variability was estimated.
The analysis of lomitapide included 13 participants with evaluable data in both periods, compared with 15 enrolled. The record describes analyte-specific exclusions for M1 and M3, with one reason incompletely stated. These analysis details define the available population but do not show whether the included participants were representative of everyone enrolled.
In general, a pharmacokinetic study of this kind addresses concentration patterns and their variability; it does not, by itself, answer broader questions about clinical outcomes. The registry record does not report clinical outcome comparisons, and the study did not include a separate control arm. No conclusion about treatment benefit or lack of benefit follows from the design description or from the adverse-event counts alone.
The record also does not state the statistical method for estimating within-subject variation, how incomplete observations were handled, or how the six listed outcomes were addressed analytically. Those omissions limit independent assessment of the analysis. The registry information supports a description of the study question and design, but not a quantitative interpretation of the primary pharmacokinetic result.
13. Why This Trial Matters Statistically
Within-subject variability is a distinct statistical target from differences between people. Pharmacokinetic measurements can vary across occasions for the same participant, while participants may also differ from one another. A design that repeats dosing within participants is suited to asking about the former, provided the analysis accounts for the pairing. This study’s stated objective and crossover structure make that distinction central to interpreting its results.
The endpoint also makes the measurement strategy important. Cmax is the maximum observed concentration, so its estimate depends on the sampled concentration profile and the definition of the peak. The registry lists measurements from pre dose through 168 hours post dose. The record’s sampling schedule clarifies the intended observation window, but it does not provide the numerical profiles or the method used to estimate within-subject variability.
The analysis population further matters. The registry reports 15 enrolled and 13 subjects with evaluable data in both periods for the lomitapide analysis, alongside period-specific exclusions for M1 and M3. Those details show why an estimate should be interpreted together with its population and missing-data handling. The registry does not fully report these analytic details.
Statistically, the key lesson is that a study objective, a design, and an endpoint do not substitute for the result and its uncertainty. A reader needs the estimate, an appropriate measure of precision, and enough methodological detail to understand how repeated measurements and incomplete data were handled. Those elements are not reported in the registry record, so the study’s quantitative contribution to understanding within-subject variability cannot be assessed from this record alone.
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 central limitation for interpreting this trial is that numerical primary endpoint results are not reported in the registry record. Although the endpoint is identified as Cmax and the summary format is specified as mean and standard deviation, no numerical estimates or uncertainty measures are available. The magnitude and precision of within-subject variability therefore cannot be assessed.
The statistical method used to estimate intra-subject variability is also not reported. The record does not state how paired measurements, study periods, sequence, or possible period effects were handled. It does not describe a statistical analysis plan, hypothesis test, confidence interval method, or model assumptions. These omissions make it difficult to reproduce or independently evaluate the intended analysis.
The analyzed population was smaller than enrollment: 13 subjects with evaluable data in both periods were included in the lomitapide analysis, while 15 subjects were enrolled. The record describes exclusions for M1 and M3 by period, including an early termination and another exclusion whose explanation is incomplete. Missing-data methods and sensitivity analyses are not reported, so the effect of incomplete measurements on interpretation is unknown.
The study was open-label and had no separate control group or randomized allocation. These design features are described in the registry, but their consequences for the specific pharmacokinetic analysis cannot be fully evaluated without further methodological information. The registry also lists six outcome measures without listing analyses or a multiplicity strategy. Finally, adverse-event counts are recorded by period, but the record does not provide detailed event terms or clarify participant overlap across the period-specific counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Determine the Intra-subject Variability of Pharmacokinetics of Lomitapide in Healthy Subjects — NCT01915771.
- Registry record last updated 2020-03-11; status last verified 2020-02.
- Results first posted 2020-03-11.
- 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
This completed Phase 1, open-label crossover study enrolled 15 healthy subjects to examine intra-subject pharmacokinetic variability after two single oral doses of 20 mg lomitapide, separated by at least a 14-day washout. The primary endpoint was Cmax, defined as the maximum observed concentration of lomitapide and metabolites M1 and M3. Sampling was scheduled from pre dose through 168 hours post dose.
The lomitapide pharmacokinetic analysis included 13 subjects with evaluable data in both periods. The registry lists six outcome measures and no analyses. It does not report numerical Cmax findings, an estimate of within-subject variability, uncertainty measures, or the statistical method used. Period-specific serious-event counts were zero in both periods; other-event counts were four of 15 in Period 1 and one of 13 in Period 2, with zero deaths in each period.