An Assessment of Prasugrel on Healthy Adults and Sickle Cell Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Assessment of Prasugrel on Healthy Adults and Sickle Cell Adults (NCT01178099), a non-randomized phase 1 study. The primary outcome is Area Under the Plasma Concentration-Time Curve (AUC) From Time of Dosing Through the Sampling Time of the Last Quantifiable Concentration [AUC(0-tlast)] for Prasugrel's Active Metabolite, R-138727.

2. Clinical Question

3. Trial Design

This was a completed phase 1, non-randomized, unmasked, parallel study sponsored by Eli Lilly and Company. The registry records an enrollment of 26. The study started in 2010-07 and had primary completion in 2011-01. Its stated purpose was to measure exposure to prasugrel’s active metabolite and pharmacodynamic effects in people with sickle cell disease.

The study included healthy adults and adults with sickle cell disease. Participants received prasugrel, with the dose after the initial dose determined by body weight: 5 mg/day for participants weighing less than 60 kg or 7.5 mg/day for participants weighing at least 60 kg. The regimen was a single 10 mg dose on Day 1 followed by either daily dose for an additional 11 days. The registry’s adverse-event groups distinguish the populations and dosing regimens.

Because allocation was non-randomized and masking was absent, differences between groups cannot be interpreted as if they arose from randomized assignment. Population and dose group are part of the study structure, and the registry does not describe a separate untreated or placebo control. The record does not report the rationale for choosing this design, the criteria used to assign participants to dose groups, or a sample-size justification.

The primary endpoint was a pharmacokinetic measure, while the listed secondary outcomes included platelet aggregation measures and exposure measures for inactive metabolites. This design can describe the measurements collected under the specified regimen. It does not, by itself, establish that a difference between population or dose groups was caused by the drug or by population status.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 dose of the study drug and have evaluable data, excluding participants with an adverse event (AE) of vomiting that occurred at or before 4-hours postdose.

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 Area Under the Plasma Concentration-Time Curve (AUC) From Time of Dosing Through the Sampling Time of the Last Quantifiable Concentration [AUC(0-tlast)] for Prasugrel's Active Metabolite, R-138727, measured over Time of dosing up to 8 hours post-dose on Day 1 and Day 12.

The primary endpoint was the area under the plasma concentration-time curve, or AUC, for prasugrel’s active metabolite R-138727. It covered the period from dosing through the last quantifiable plasma concentration, with sampling up to 8 hours after dosing on Day 1 and Day 12. The registry describes the unit as nanogram*hour per milliliter and reports that geometric least-squares means were obtained.

As a general pharmacokinetic concept, AUC represents exposure across a period of concentration measurement: it incorporates both the concentrations observed and the time over which they are observed. It is useful when the question concerns the amount of drug-related substance circulating over a sampling interval, rather than a single concentration at one time. The endpoint is not itself a direct measure of a clinical outcome.

The registry states that log-transformed AUC was analyzed with a mixed effect model. It identifies dose, population, and their interaction as fixed effects, with participant as a random effect. These details describe the planned statistical representation of the endpoint. The numerical geometric means, their confidence intervals, and any model-based contrasts are not reported in the registry record, so the size and precision of the observed exposure estimates cannot be described from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is an AUC measurement with units of nanogram*hour per milliliter. A continuous outcome can take a range of values rather than representing a category such as an event or no event. The registry identifies the reported summary as a geometric least-squares mean and the accompanying uncertainty measure as a 95% confidence interval. The actual means and interval limits are not reported in the registry record.

Why use a log transformation?

The record states that AUC was log-transformed before analysis. In general, a logarithmic transformation changes the scale on which a continuous outcome is modeled. It can be useful for positive measurements whose variability is more naturally expressed proportionally than as a fixed additive amount. That is a general statistical rationale; the registry does not report a specific diagnostic or distributional rationale for the transformation in this study.

After analysis on the log scale, estimates can be expressed back on the original measurement scale as geometric means. A geometric mean summarizes values through multiplicative rather than arithmetic averaging. It should not be read as the ordinary arithmetic average. The registry states that geometric least-squares means were obtained, but does not give the estimates or explain any additional back-transformation details.

What does the mixed effect model represent?

The model included dose, population, and the dose-by-population interaction as fixed effects. Fixed effects represent the particular explanatory factors named in the analysis, rather than a sample of possible levels intended to represent a larger random set of levels. Here, dose and population are the factors identified in the registry, and the interaction allows the association of dose with the modeled endpoint to differ by population.

Participant was included as a random effect. In general, a participant-level random effect can account for the fact that repeated measurements from the same participant may be related. This is relevant to a study measuring AUC at more than one study time point. The registry does not give further details about the covariance structure, estimation method, model diagnostics, or the exact form of any contrasts.

The model description does not tell a reader the resulting effect estimates. To assess the primary endpoint quantitatively, one would need the reported group estimates and their uncertainty, and, for a comparison, the relevant model-based contrast. Those numerical results are not reported in the registry record. It would not be appropriate to infer a contrast from the model specification alone.

How should the confidence interval be read?

In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater statistical precision than a wider interval on the same scale, while neither width nor location alone establishes clinical importance. The registry identifies a 95% confidence interval for the primary outcome summary, but the interval endpoints are not reported. Consequently, neither the precision of the estimates nor the range of values compatible with the analysis can be assessed.

Confidence intervals are also tied to the population and model used to calculate them. The primary analysis population comprised participants who received at least one dose and had evaluable data, excluding participants with vomiting at or before 4-hours postdose. This makes the intended analysis set narrower than a simple description of all enrolled participants. The record does not state how evaluability was determined or how missing outcome data outside that exclusion were treated.

What do the planning assumptions mean?

The registry describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the study had a particular probability of detecting an effect after the data were collected. The planning outputs and the trial’s own sample-size justification are not reported in the registry record.

These assumptions also need to be separated from the actual design. The trial was non-randomized, and its group structure should not be assumed to meet the equal-allocation assumption used for an illustration. The registry record does not establish that the planning assumptions governed enrollment or the primary analysis. No conclusion about achieved power can be drawn from them.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and 39 analyses. The primary outcome concerns AUC for the active metabolite. The listed secondary outcomes include platelet aggregation measures at Day 12, using 5 micromolar and 20 micromolar ADP, and exposure measures for inactive metabolites. Multiple outcomes and analyses create opportunities for findings to vary by measure or analysis choice. As a general statistical issue, interpreting many tests without an appropriate plan can increase the chance of emphasizing a result that appears notable by chance.

A multiplicity adjustment, a hierarchy for testing outcomes, or another prespecified approach to controlling the overall error rate is not reported in the registry record. The record also does not report whether secondary outcomes were considered exploratory or how inferences across them were intended to be made. This limits interpretation of any isolated result, even if numerical results were available.

The primary analysis population is described as participants who received at least one dose and had evaluable data, excluding participants with an adverse event of vomiting at or before 4-hours postdose. This definition clarifies an important eligibility condition for the analysis. The number of participants contributing data to each endpoint, the rules for determining evaluability, and the handling of other missing measurements are not reported in the registry record.

The record does not report whether imputation, a missing-data sensitivity analysis, or a particular approach to incomplete repeated measurements was used. It also does not report whether all participants were analyzed according to their initial group assignment or whether any participants changed analysis groups. These omissions prevent a fuller assessment of how missingness and analysis-set selection may affect the estimates.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 event counts by group. For Prasugrel 10/5 mg Healthy Participants, 0 of 4 participants at risk were recorded as affected; for Prasugrel 10/7.5 mg Healthy Participants, 0 of 9 were affected. The combined healthy-participant group reports 0 of 13. For Prasugrel 10/5 mg Sickle Cell Disease, 0 of 4 were affected; for Prasugrel 10/7.5 mg Sickle Cell Disease, 0 of 9 were affected. The combined sickle-cell-disease group reports 0 of 13.

These are counts within the registry’s stated at-risk groups, not estimates of comparative risk. Because the study was non-randomized and has no like-for-like control comparison, the figures do not establish a relative safety effect. No serious-event terms are listed in the record. Death counts are not reported in the registry record.

The registry separately reports other, non-serious adverse events: 3 of 4 in the 10/5 mg healthy group, 5 of 9 in the 10/7.5 mg healthy group, and 8 of 13 in the combined healthy group; the corresponding sickle-cell-disease groups report 3 of 4, 7 of 9, and 10 of 13. These group counts should be read as reported, without adding overlapping subgroup and combined-group entries. The figures do not identify event severity beyond the serious versus other distinction or establish causality.

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

This study addresses pharmacokinetic and pharmacodynamic measurement in healthy adults and adults with sickle cell disease receiving prasugrel. Its primary endpoint is exposure to the active metabolite R-138727, measured by AUC over the specified sampling period. The record also lists platelet aggregation outcomes and measures of inactive-metabolite exposure. These features make the study’s focus clear: it describes drug-related measurements under the regimen recorded.

The registry record does not report numerical results for the primary endpoint. It therefore does not permit a quantitative conclusion about the active-metabolite exposure, the precision of an estimate, or the magnitude of any group difference. The model description and endpoint definition explain the intended analysis but cannot replace estimates and uncertainty intervals.

Nor does the record establish that any observed difference would be caused by treatment or population status. The study was non-randomized and unmasked, and dose was associated with participant weight. The listed groups are not a randomized treatment-versus-control comparison. Comparisons across them may be affected by differences in the groups or by the way participants entered them.

The adverse-event counts describe the registry’s recorded serious and other adverse events in the listed groups. They are not a basis for comparing safety against an untreated or randomized control group. The record’s serious-event counts are zero for the listed groups, while death counts are not reported in the registry record; these registry entries should not be extended beyond the recorded categories and groups.

In general, a pharmacokinetic study can characterize exposure and support further questions about how measurements vary across groups or over time. It does not, on its own, answer whether a regimen improves health outcomes. The registry record supports description of the study’s aim, methods, and reported safety counts, but does not provide the numerical primary outcome results needed to assess the observed exposure.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a small phase 1 study can define a pharmacokinetic endpoint and model repeated measurements across dose and population factors. The primary AUC measure is linked to a specified plasma sampling window, and the record identifies a log-scale mixed effect analysis with participant-level variation. Those choices make clear which statistical features the investigators intended to address.

The study also illustrates why design details are essential when reading group comparisons. Allocation was non-randomized, masking was absent, and dose depended on weight. The registry describes groups by dose and population, not a randomized control comparison. A statistical model can account for specified factors, but it cannot by itself make non-randomized groups exchangeable or remove unmeasured differences.

There is also an important distinction between methods and results. The registry gives an endpoint definition, an analysis population, and a model description, yet numerical primary outcome estimates are not reported in the registry record. Without estimates and confidence intervals, the analysis cannot be assessed for observed magnitude or precision. This underscores the value of reporting effect estimates and uncertainty alongside methods.

Finally, the record lists multiple outcomes and analyses, while multiplicity handling and broader missing-data methods are not reported. Those omissions matter because readers need to know how outcome selection, repeated measurements, and incomplete data were handled to interpret a full set of findings. The trial is therefore useful for illustrating both what a clearly defined analysis can communicate and the limits imposed when outcome results and key analytic details are absent.

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 main question is that numerical AUC results are not reported in the registry record. The record gives neither group estimates nor confidence interval limits, so the observed exposure and its precision cannot be described. Although 95% confidence intervals are identified as the uncertainty measure, their values are absent.

The non-randomized, unmasked design restricts interpretation of comparisons among groups. There is no like-for-like randomized control comparison, and dose was assigned according to weight categories. The registry does not report the allocation process or explain how potential differences among the groups were addressed beyond the stated model factors.

The registry describes an analysis population that excludes participants with vomiting at or before 4-hours postdose and requires evaluable data. It does not report the number included in the primary analysis, the criteria for evaluability, or the handling of other missing data. This leaves uncertainty about the impact of exclusions and incomplete measurements.

The record lists 15 outcome measures and 39 analyses but does not report a multiplicity strategy. It also does not provide details such as model diagnostics, covariance structure, or sensitivity analyses. These details are not necessary to identify the stated model, but their absence limits assessment of its implementation and robustness.

Finally, the study was phase 1 and enrolled 26 participants, with groups defined by health status and dose. The findings, even if fully reported, would need to be interpreted in the context of this design and enrollment rather than treated as a randomized clinical outcome comparison. A sample-size justification is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Assessment of Prasugrel on Healthy Adults and Sickle Cell Adults — NCT01178099.
• Registry record last updated 2012-02-15; status last verified 2012-01.
• Results first posted 2012-02-15.
• 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

The registry describes a completed phase 1 study of prasugrel in healthy adults and adults with sickle cell disease. It was non-randomized, unmasked, and parallel, with an enrollment of 26. Participants received a single 10 mg dose on Day 1 followed by 5 mg/day or 7.5 mg/day for an additional 11 days, according to the weight categories specified in the record.

The primary endpoint was AUC for the active metabolite R-138727, measured through the last quantifiable concentration, with sampling up to 8 hours after dosing on Day 1 and Day 12. The registry describes a log-transformed mixed effect model and a defined analysis population. Numerical primary endpoint estimates and confidence intervals are not reported in the registry record. Serious adverse event counts are reported as zero in the listed groups; death counts are not reported.