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 Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158) (NCT01583647), a randomized phase 1 study. The primary outcome is Plasma Area Under the Concentration Curve From 0 to Infinity (AUC0-∞) of Laropiprant.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01583647 |
| Phase | Phase 1 |
| Condition | Hypercholesterolemia, Familial, Heterozygous Familial Hypercholesterolemia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Adolescents with heterozygous familial hypercholesterolemia were the intended study population. The condition is also listed as familial hypercholesterolemia. The registry record does not report further participant characteristics, such as age ranges or baseline lipid values.
Intervention
Panel A was assigned a single oral dose of one MK-0524A tablet, containing extended-release niacin 1 g and laropiprant 20 mg. The study description identifies pharmacokinetics after a single dose as its purpose. The registry record does not report additional dosing or follow-up beyond the stated endpoint timeframe.
Comparator
Panel B was planned to receive a single oral dose of two MK-0524A tablets, with each tablet containing extended-release niacin 1 g and laropiprant 20 mg. Panel B was not conducted. Therefore, the registry record contains no completed comparison between the one-tablet and two-tablet regimens.
Primary question
The named primary endpoint was plasma area under the concentration curve from 0 to infinity for laropiprant, with the timeframe stated as predose Day 1 up to 24 hours postdose. The central question was about laropiprant pharmacokinetics after the planned single-dose regimens. The study was terminated during Panel A, and the decision was made not to analyze the blood and urine pharmacokinetic samples collected during that panel. Consequently, the registry record reports no primary endpoint estimate and no result answering that question.
3. Trial Design
The registry record classifies this as a Phase 1 study with randomized allocation, no masking, and a parallel model. It lists total enrollment as 10. The study title and summary describe a single-dose investigation of extended-release niacin/laropiprant in adolescents with heterozygous familial hypercholesterolemia, focused on laropiprant pharmacokinetics. The record identifies two planned panels: one tablet in Panel A and two tablets in Panel B.
The planned Panel A dose was one oral tablet containing extended-release niacin 1 g and laropiprant 20 mg. The planned Panel B dose was two such tablets. Although randomization is recorded, the method used to generate the allocation sequence, the assignment ratio, and the allocation concealment procedures are not reported in the registry record. The record also does not report a masking procedure beyond classifying the study as having none.
The study was terminated. The record states that termination occurred during Panel A, that the decision was made not to analyze the blood and urine pharmacokinetic samples collected in that panel, and that Panel B was not conducted. Thus, the planned parallel comparison did not reach completion. The registry record does not report why the study was terminated or whether the participants enrolled were distributed across any intended groups.
The start and primary completion dates are listed as 2012-06 and 2012-12. The registry record does not report a protocol-level sample-size justification, a detailed statistical analysis plan, or the operational details of randomization. The enrollment total should not be interpreted as the number contributing to a pharmacokinetic analysis: those samples were not analyzed.
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: MK-0524A-158 was terminated after the Phase 3 study HPS2-THRIVE (MK-0524A-042;NCT00461630) didn't meet its primary endpoint of reduction of major vascular events; there was also a significant increase in some types of non-fatal serious adverse events. MK-0524A-158 was terminated after 10 participants completed Panel A. Panel B was not conducted.
Overall Study
| Stage | MK-0524A 1 g/20 mg (Panel A) | MK-0524A 2 g/40 mg (Panel B) |
|---|---|---|
| STARTED | 10 | 0 |
| COMPLETED | 10 | 0 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The study was terminated during Panel A and the decision was made to not analyze the blood and urine pharmacokinetic samples collected during Panel A; Panel B was not conducted.
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 | MK-0524A 1 g/20 mg (Panel A) |
|---|---|---|
| Participants analysed | 10 | |
| Age, Continuous | Years | 15.4 (SD 0.8) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Plasma Area Under the Concentration Curve From 0 to Infinity (AUC0-∞) of Laropiprant, measured over Predose Day 1 up to 24 hours postdose.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is named as plasma area under the concentration curve from 0 to infinity (AUC0-∞) of laropiprant. The timeframe is listed as predose Day 1 up to 24 hours postdose. No unit or endpoint value is reported in the registry record.
General explanation: an area under a concentration-time curve represents integrated drug concentration across time. It is used in pharmacokinetic studies to describe overall exposure, rather than concentration at just one sampling time. Extending the stated curve to infinity generally refers to accounting for exposure beyond the observed sampling window; the exact calculation and assumptions used in this study are not reported in the registry record.
The endpoint could have addressed laropiprant exposure after the planned single-dose regimen, but an endpoint definition is not an endpoint result. The record specifically says that the Panel A blood and urine pharmacokinetic samples were not analyzed and that Panel B was not conducted. It therefore reports no AUC estimate, variability measure, confidence interval, or comparison for this endpoint. The stated 24-hour sampling timeframe does not establish what data would have been available for extrapolation or how any extrapolation would have been performed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes that a randomized, unmasked, parallel Phase 1 study was planned, with two single-dose panels. It does not establish a pharmacokinetic finding. The primary endpoint is identified, but the record says that the samples collected during Panel A were not analyzed and Panel B was not conducted. No primary endpoint estimate or analysis result is reported.
This distinction matters because the presence of an endpoint name does not mean that an endpoint was measured and analyzed successfully. Without an AUC estimate, there is no reported exposure value to describe, no uncertainty interval to assess, and no statistical comparison to interpret. The record also reports zero analyses. It does not provide a p-value, a standard error, a confidence interval, or an estimated treatment contrast for the primary endpoint.
The intended regimen contrast cannot be reconstructed from the record. Panel A specified one tablet and Panel B specified two tablets, but the second panel did not take place. There is therefore no completed comparison between those planned regimens. Randomized allocation is recorded as a design feature, but randomization alone does not create a comparative result when the planned data are not analyzed and one panel was not conducted.
The safety information is separate from the missing pharmacokinetic result. For Panel A, 10 participants are listed as at risk for serious adverse events, with 0 affected; 10 are listed as at risk for other adverse events, with 7 affected. Panel B has no participants at risk because it was not conducted. These counts describe the posted safety record only. They do not provide a substitute for the primary endpoint or establish a pharmacokinetic comparison.
General explanation: an estimate describes the observed size of a quantity, while its uncertainty describes how precisely that quantity has been estimated under an analysis. A confidence interval, when reported, gives a range of values compatible with the data and analysis assumptions. No such estimate or interval appears for the primary endpoint in this record. It is consequently not possible to assess the magnitude or precision of laropiprant exposure from the posted results.
The record also does not report why termination occurred. That absence prevents a reader from distinguishing among possible operational or scientific reasons; none should be inferred from the termination status alone. The appropriate statistical interpretation is limited: the study was initiated and terminated during Panel A, the intended pharmacokinetic samples were not analyzed, and no primary pharmacokinetic result is reported.
9. Statistical Methods Explained
Design and allocation. The registry record describes the study as randomized, unmasked, and parallel. General explanation: randomization is intended to make treatment assignment independent of participant characteristics on average, supporting fair comparisons when groups are followed and analyzed as planned. It does not guarantee balance in a small study, and it cannot compensate for a comparison that was not completed. The method of sequence generation, concealment, and allocation ratio are not reported in the registry record.
What an endpoint analysis would ordinarily describe. The designated endpoint is laropiprant AUC0-∞. General explanation: an analysis of a continuous pharmacokinetic endpoint would ordinarily report an estimate along with a measure of uncertainty, and, for a planned group comparison, would describe the contrast and its uncertainty. Those quantities help distinguish the estimated exposure from the precision of that estimate. No endpoint estimate, contrast, or uncertainty measure is reported for this study. The registry record says the relevant Panel A samples were not analyzed and Panel B was not conducted.
Uncertainty and statistical tests. General explanation: a confidence interval communicates a range of estimates that are compatible with the observed data under the analysis assumptions. A p-value addresses how compatible the observed data are with a specified null model, also under assumptions; it is not a measure of effect size or the probability that a hypothesis is true. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record. No hypothesis test for the intended panel comparison is reported.
Planning assumptions. The registry record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect, and distinguishes participant counts per arm from total event counts for time-to-event illustrations. These are planning assumptions, not the study's own design justification. The registry record does not report a trial-specific sample-size justification. Since no analyzed primary endpoint effect is reported, there is no posted observed effect from which to interpret a planning illustration. Such illustrations are not observed power and do not demonstrate that the study could detect an effect.
Small studies and precision. General explanation: with limited data, estimates can be imprecise, and a lack of statistical significance, if a test is performed, does not by itself show that groups are equivalent. Precision depends on the information actually analyzed and the variability of the outcome. In this record, there is no analyzed pharmacokinetic endpoint from which to assess either variability or precision. The enrollment total alone cannot establish an endpoint sample size or the precision of an estimate.
Over-dispersion and distribution. General explanation: over-dispersion occurs when variability in observed data exceeds what a chosen statistical model expects. It can make model-based uncertainty too small if the extra variability is not accounted for. Pharmacokinetic data may require methods suited to their distribution and sampling structure, but the registry record does not report a distributional model, a transformation, or any assessment of over-dispersion. No particular method should be attributed to this study.
Analysis populations and adjustment. General explanation: an analysis population defines which participants' data contribute to a result. Some analyses may use all randomized participants, while others may require evaluable samples or adherence to specified criteria. The registry record does not report an analysis population, participant-level exclusions, covariate adjustment, or handling of protocol deviations. Because the planned samples were not analyzed, the record does not identify a population used for the primary pharmacokinetic analysis.
What can be concluded from the methods record. The design labels and the planned endpoint are documented, but the analysis methods and results needed to interpret that endpoint are not. No statistical model, standard error method, confidence-interval method, or multiplicity procedure is reported in the registry record. General methodological explanations describe how such analyses may be interpreted; they do not establish that any of these procedures were used in this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists four outcome measures and zero analyses. It names a primary pharmacokinetic endpoint, but does not report an analyzed result for it. No analysis of additional outcome measures is reported. The record does not describe a hierarchy of endpoints, a multiplicity adjustment, or a procedure for controlling the chance of false-positive findings across multiple tests. Any such plan is not reported in the registry record.
Missing data require particular care in this study because the planned pharmacokinetic samples were not analyzed. The record does not explain whether the samples were unavailable, incomplete, technically unsuitable, or excluded for another reason. It also does not report an imputation method, a sensitivity analysis, or a rule for handling values below quantification limits. Those details are not reported in the registry record, and no reason for the non-analysis should be inferred.
The study's termination and the absence of Panel B also limit the intended comparison. The registry record does not describe an analysis population or the disposition of participants by panel. It does not report an interim-analysis plan, stopping boundary, or other monitoring procedure. Because the record gives no analyzed primary endpoint result, there is no reported basis for assessing multiplicity-adjusted or unadjusted statistical evidence.
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 |
|---|---|---|---|
| MK-0524A 1 g/20 mg (Panel A) | 0 | 10 | 0.0% |
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 |
|---|---|
| MK-0524A 1 g/20 mg (Panel A) | 7 of 10 |
| MK-0524A 2 g/40 mg (Panel B) | 0 of 0 |
Most frequent non-serious adverse event terms
| Event term | Organ system | MK-0524A 1 g/20 mg (Panel A) | MK-0524A 2 g/40 mg (Panel B) |
|---|---|---|---|
| Headache | Nervous system disorders | 2 of 10 | 0 of 0 |
| Abdominal pain lower | Gastrointestinal disorders | 1 of 10 | 0 of 0 |
| Bruising of arm | Injury, poisoning and procedural complications | 1 of 10 | 0 of 0 |
| Sprain | Injury, poisoning and procedural complications | 1 of 10 | 0 of 0 |
| Low back pain | Musculoskeletal and connective tissue disorders | 1 of 10 | 0 of 0 |
| Diuresis | Renal and urinary disorders | 1 of 10 | 0 of 0 |
| Pruritus | Skin and subcutaneous tissue disorders | 1 of 10 | 0 of 0 |
| Facial flushing | Vascular disorders | 1 of 10 | 0 of 0 |
| Flushing | Vascular disorders | 1 of 10 | 0 of 0 |
For Panel A, the registry record lists 10 participants at risk for serious adverse events and 0 affected. It lists 10 participants at risk for other adverse events and 7 affected. The record does not list any serious adverse event terms. Death counts are not reported in the registry record.
Panel B lists 0 participants at risk and 0 affected for both serious and other adverse events. This panel was not conducted, so those zeros reflect the absence of participants at risk in that panel, not evidence that participants who received the planned two-tablet dose experienced no events.
General explanation: safety counts should be read with their at-risk group and the period of observation in mind. A count of participants affected does not convey event severity, duration, recurrence, or causal attribution unless those details are reported. The registry record does not provide those details for the other adverse events. These safety entries are descriptive counts and are not a comparison of the planned regimens.
12. What the Result Does, and Does Not, Mean
The record supports a limited account of what was planned and what was completed. It describes a randomized, unmasked Phase 1 study of single-dose extended-release niacin/laropiprant in adolescents with heterozygous familial hypercholesterolemia. One panel planned one tablet and another planned two tablets. The study was terminated during Panel A; the Panel A pharmacokinetic samples were not analyzed, and Panel B was not conducted.
The record does not establish the amount of laropiprant exposure after either regimen. It reports no primary AUC result, no comparison between regimens, and no estimate of uncertainty. It also does not explain why the study was terminated. The planned endpoint and the safety counts cannot fill those gaps.
General explanation: a study's design describes how investigators intend to collect and compare data; the result depends on what data are collected and analyzed. A randomized design can support causal comparisons when the relevant groups and outcomes are observed and analyzed appropriately. It does not, by itself, supply evidence about a treatment when the comparison was not completed.
The safety entries show the posted counts for Panel A and the absence of an at-risk group in Panel B. They should not be interpreted as comparative safety evidence. The registry record does not report enough detail to characterize the other adverse events beyond the number of participants affected, and it does not report death counts.
Accordingly, the statistical meaning is primarily about the limits of inference: a pharmacokinetic question was posed, but no analyzed primary endpoint result is reported. The record neither establishes nor rules out a difference between the planned regimens. It also does not provide a basis for generalizing a pharmacokinetic estimate to a broader population, because no such estimate is reported and participant characteristics beyond the stated condition are not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates why design labels and outcome definitions must be separated from completed statistical evidence. The record identifies randomization, a parallel model, an intended primary endpoint, and two planned dose panels. Those details explain the intended structure of the research, but they do not amount to an estimate of laropiprant exposure. The study stopped before the planned comparison was completed, and the collected Panel A pharmacokinetic samples were not analyzed.
For statistical interpretation, an unreported endpoint is not a null finding. A null finding would still require analyzed data and an estimate, with uncertainty, to show what the data indicate. Here, the registry record reports no primary endpoint estimate or analysis. It is therefore not possible to judge the size, direction, or precision of any pharmacokinetic difference.
The record also demonstrates the value of reading safety denominators in context. Panel A has participants listed at risk, while Panel B has none because it was not conducted. Treating the Panel B zeros as observed evidence of no events would confuse the absence of exposure with an observed safety outcome.
General explanation: transparent reporting of study status, analysis populations, missing data, and estimates helps readers distinguish completed findings from planned questions. In this case, the documented termination and non-analysis are essential to interpreting what the registry record can and cannot support. The record is informative about study conduct and the limits of available inference, even though it does not provide the planned pharmacokinetic result.
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 main trial-specific limitation is that the primary pharmacokinetic samples collected during Panel A were not analyzed, and Panel B was not conducted. No primary endpoint estimate or comparison is reported. The termination reason is not reported in the registry record, so its consequences cannot be explained beyond the stated interruption of the planned study.
The record lists enrollment as 10, but does not report how participants were allocated or provide a participant disposition by panel. It therefore does not establish the number with evaluable pharmacokinetic samples, and the enrollment total should not be treated as an analysis sample size. The analysis population is not reported in the registry record.
The endpoint timeframe is stated as predose Day 1 up to 24 hours postdose, while the endpoint is named as AUC0-∞. The registry record does not describe the sampling schedule, the calculation of the area beyond the stated observation period, or the assumptions used for any extrapolation. No endpoint unit is reported.
The record does not report baseline participant characteristics, a detailed analysis plan, a sample-size justification, a multiplicity procedure, or methods for handling missing data. It also does not provide detail about the type, severity, duration, or attribution of the other adverse events. These absences limit interpretation, and none should be filled by assumptions about standard practice.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158) — NCT01583647.
- Registry record last updated 2015-11-03; status last verified 2015-11.
- Results first posted 2013-12-04.
- 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.
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18. Record Summary
The registry record describes NCT01583647, a randomized, unmasked, parallel Phase 1 study of single-dose extended-release niacin/laropiprant in adolescents with heterozygous familial hypercholesterolemia. Enrollment is listed as 10. Panel A planned one tablet containing extended-release niacin 1 g and laropiprant 20 mg; Panel B planned two tablets with the same amount in each tablet.
The study is listed as terminated. It ended during Panel A, the Panel A blood and urine pharmacokinetic samples were not analyzed, and Panel B was not conducted. The named primary endpoint was laropiprant AUC0-∞, with a stated timeframe from predose Day 1 up to 24 hours postdose. No primary endpoint result or analysis is reported.
For Panel A, the record lists 0 serious adverse events among 10 at risk and 7 participants with other adverse events among 10 at risk. Panel B had no participants at risk. The record does not report the termination reason, analysis population, or detailed statistical methods.