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 Effect of Food on the Pharmacokinetics of Apremilast (CC-10004) in Healthy Adults (NCT01634178), a randomized phase 1 study. The primary outcome is Maximum Observed Plasma Concentration (Cmax) of Apremilast.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01634178 |
| Phase | Phase 1 |
| Condition | Healthy Volunteer |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 46 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Amgen |
| Results posted | Yes |
2. Clinical Question
Population
Healthy adults. The registry lists the condition as Healthy Volunteer and reports an enrollment of 46 participants.
Intervention
A single 30 mg tablet of apremilast administered after a high-fat meal.
Comparator
A single 30 mg tablet of apremilast administered under fasted conditions. Participants received the fed and fasted conditions in opposite orders across the two treatment periods.
Primary question
How did the maximum observed plasma concentration of apremilast compare between fed and fasted conditions?
The study addresses a pharmacokinetic question: whether taking apremilast after a high-fat meal is associated with a different measured plasma concentration than taking it while fasted. The primary endpoint was maximum observed plasma concentration, or Cmax. It describes the highest measured concentration in the sampling profile after dosing; it is not a measure of clinical benefit.
The registry reports a ratio of geometric least squares means of 98.3, with a 90% confidence interval from 90.7 to 106.6, for the fed and fasted comparison. It does not report a p-value for this analysis. The posted result therefore describes an estimated relative concentration and the uncertainty around that estimate, rather than establishing a clinical consequence of the meal condition.
These findings concern a single dose in healthy adults. The record does not report results for repeated dosing, people with a health condition, or outcomes other than the listed pharmacokinetic and adverse-event measures. Those questions are outside the scope of the registered comparison.
3. Trial Design
This was a Phase 1, randomized, open-label, two-period, two-sequence crossover study. The registry lists an enrollment of 46 and describes the study as completed. It names Amgen as the sponsor. The study started on 2012-02-01, and primary completion was recorded on 2012-03-01.
In a crossover design, participants receive more than one treatment condition across separate periods. In this study, the conditions were a single 30 mg apremilast tablet under fasted conditions and a single 30 mg tablet after a high-fat meal. One sequence received fasted treatment in Period 1 and fed treatment in Period 2; the other sequence received fed treatment in Period 1 and fasted treatment in Period 2. Randomization assigned participants to a sequence.
General statistical context: a crossover comparison can use each participant’s measurements under both conditions, which may help account for stable differences between participants. That design feature does not establish which model or paired analysis was used. The analysis method is not reported in the registry record.
The study was open-label, so masking was not used. The primary outcome was maximum observed plasma concentration of apremilast. Plasma concentrations were determined using a validated liquid chromatography-tandem mass spectrometry assay. The listed sampling schedule covered Day 1 of each treatment period, from pre-dose through 48 hours after dosing. The registry does not describe the interval between periods or other operational details of the crossover.
The pharmacokinetic population included participants who received at least one dose and had evaluable pharmacokinetic profiles. The posted arm summaries list 45 participants for fasted treatment and 44 for fed treatment. These counts describe the displayed endpoint summaries; the registry does not explain why the endpoint denominators differ from each other or from enrollment.
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: The study consisted of 2 periods. Participants were randomly assigned to one of two treatment sequences; Fasted then Fed or Fed then Fasted. Each participant was to receive 1 dose of apremilast under fasted conditions and 1 dose of apremilast under fed conditions in each period, respectively, depending on their sequence assignment. There was a 5 to 10 day washout period between each dose.
Treatment Period 1
| Stage | Sequence 1: Apremilast Fasted / Fed | Sequence 2: Apremilast Fed / Fasted |
|---|---|---|
| STARTED | 23 | 23 |
| COMPLETED | 23 | 22 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Sequence 1: Apremilast Fasted / Fed | Sequence 2: Apremilast Fed / Fasted |
|---|---|---|
| Adverse Event | 0 | 1 |
Treatment Period 2
| Stage | Sequence 1: Apremilast Fasted / Fed | Sequence 2: Apremilast Fed / Fasted |
|---|---|---|
| STARTED | 23 | 22 |
| COMPLETED | 22 | 22 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Sequence 1: Apremilast Fasted / Fed | Sequence 2: Apremilast Fed / Fasted |
|---|---|---|
| Adverse Event | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic (PK) population included all participants who received at least 1 dose of apremilast and had evaluable PK profiles.
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 | Apremilast |
|---|---|---|
| Participants analysed | 46 | |
| Age, Continuous | years | 38.5 (SD 13.45) |
| Sex: Female, Male: Female | Participants | 25 |
| Sex: Female, Male: Male | Participants | 21 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 17 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 29 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race/Ethnicity, Customized: White | Participants | 31 |
| Race/Ethnicity, Customized: Black or African American | Participants | 13 |
| Race/Ethnicity, Customized: Asian | Participants | 1 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Observed Plasma Concentration (Cmax) of Apremilast, measured over Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing..
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | ng/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was maximum observed plasma concentration, or Cmax, of apremilast, measured in ng/mL. It is the highest concentration recorded among the scheduled plasma samples after a dose. The registry specifies a geometric mean as the summary measure and a geometric coefficient of variation as the measure of dispersion.
General statistical context: Cmax is used in pharmacokinetic studies to describe the peak concentration reached during the observed sampling period. Comparing this measure across fed and fasted conditions can describe whether the meal condition is associated with a change in the observed peak concentration. It does not by itself describe the full concentration-time profile, the total amount of drug exposure, or a clinical outcome.
The sampling schedule was on Day 1 of each treatment period, with measurements at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing. The registry states that the assay was validated, but does not report further assay-performance details.
Geometric summaries are useful for concentration measures that are commonly summarized multiplicatively rather than by arithmetic averages. The posted results report geometric means of 339.9 ng/mL in the fasted group and 333.9 ng/mL in the fed group. The reported geometric coefficient of variation was 26.5 for fasted treatment and 30.0 for fed treatment. These summaries describe the endpoint distributions as presented; they do not replace the reported comparison estimate or specify the analysis model.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports geometric mean Cmax values of 339.9 ng/mL for fasted treatment and 333.9 ng/mL for fed treatment. The sponsor-reported ratio of geometric least squares means is 98.3, with a 90% confidence interval from 90.7 to 106.6. No p-value is reported. These are the central posted results for the primary pharmacokinetic comparison.
The ratio expresses a relative comparison of the geometric least squares means, while the confidence interval conveys uncertainty around that estimate. The interval spans a range of values that are compatible with the reported analysis under its statistical assumptions. It indicates that the point estimate should not be read as exact. The registry record does not provide the model details or additional assumptions needed to assess the interval’s construction in depth.
General statistical context: a confidence interval is not a statement that a fixed proportion of individual participants had results within its limits. Nor does an interval, by itself, establish that two conditions are equivalent. Equivalence requires a prespecified margin and an analysis tied to that margin; such a margin is not reported in the registry record. The reported estimate and interval should therefore be read as a quantitative comparison, not as a formal equivalence conclusion.
The arm summaries are not identical: the fasted geometric mean is 339.9 ng/mL and the fed geometric mean is 333.9 ng/mL. The comparison estimate is the relevant reported analysis for the randomized crossover question; the separate arm means are descriptive summaries and do not disclose how within-participant measurements were handled. The registry reports no analysis method for the ratio.
Precision is conveyed by the width and limits of the confidence interval, but the record does not provide a separate judgment of whether that precision was adequate for a predefined decision. The registry also does not report a p-value, an equivalence margin, a protocol-based sample-size justification, or an explicit decision threshold. Without those details, the statistical result can be described, but its relationship to any prespecified inferential objective cannot be fully evaluated.
The endpoint is pharmacokinetic, not clinical. It quantifies peak plasma concentration after a single dose in healthy adults. These findings do not establish what happens with repeated dosing, in other populations, or for clinical outcomes. They also do not show that the meal condition caused any clinical change. The posted evidence supports a description of the measured Cmax comparison and its uncertainty within this study’s setting.
The registry also lists adverse-event outcomes. Those safety counts are distinct from the primary Cmax analysis and do not alter its interpretation. The record includes no reported serious adverse events in either treatment condition, but the safety data should be read with the reported denominators and the limits of the recorded information in mind.
9. Statistical Methods Explained
The primary outcome is a continuous pharmacokinetic measure: maximum observed plasma concentration. The registry presents the group summaries as geometric means, with geometric coefficients of variation, and reports a ratio of geometric least squares means with a 90% confidence interval. The analysis method itself is not reported in the registry record.
What does a geometric mean describe?
General statistical context: a geometric mean summarizes measurements on a multiplicative scale. It is often used when values vary proportionally or have a right-skewed distribution, as can occur with concentration measurements. It differs from an arithmetic mean, which summarizes values by addition. The choice of a geometric summary does not, on its own, reveal the statistical model used to estimate the comparison.
The posted geometric means are 339.9 ng/mL for fasted treatment and 333.9 ng/mL for fed treatment. The reported geometric coefficients of variation are 26.5 and 30.0, respectively. General statistical context: a coefficient of variation describes dispersion relative to a mean, and a geometric coefficient of variation is defined for multiplicative variation. It provides context about variability but is not a confidence interval for the treatment comparison.
How should the ratio and interval be read?
The reported ratio of geometric least squares means is 98.3, and its 90% confidence interval runs from 90.7 to 106.6. General statistical context: a ratio compares quantities on a relative scale, while a confidence interval reflects uncertainty in the estimated comparison. A confidence interval is not a range containing a fixed share of individual measurements. Its interpretation depends on the analysis and assumptions used to construct it.
The registry does not state the direction convention for the ratio, identify the model used to estimate the geometric least squares means, or provide a p-value. The comparison is reported for the fasted and fed groups, but the record does not spell out details such as covariates or how period and sequence were represented in the model. Those details should not be inferred from the crossover design alone.
Why does the crossover structure matter?
General statistical context: in a crossover study, participants receive conditions in different sequences, so observations from the same person can potentially be compared. That can be useful because participants may differ in their typical concentrations. Randomization of sequences helps assign the order of conditions rather than allowing participants or investigators to choose it. These design features do not guarantee that a particular paired model was used, and they do not remove the need to account for period or sequence where appropriate.
The registry describes two periods and two sequences, with each participant receiving fed and fasted treatment in opposite orders across the sequences. It does not report the interval between periods, any washout procedure, or tests for period or carryover effects. It would therefore be inappropriate to assert how those issues were addressed analytically.
What does the analysis population include?
The pharmacokinetic population included participants who received at least one dose and had evaluable pharmacokinetic profiles. This definition means the primary analysis was not described simply as every enrolled participant regardless of data availability. The posted Cmax summaries list 45 participants for fasted treatment and 44 for fed treatment, while the enrollment was 46. The record does not give reasons for the endpoint counts or say how many participants contributed paired measurements to the comparison.
General statistical context: excluding participants without evaluable profiles can affect which participants contribute to an endpoint analysis. The impact depends on why measurements are unavailable and on the analysis approach. The registry record does not report missing-data methods, imputation, or sensitivity analyses for the pharmacokinetic outcome.
What is known about planning and multiplicity?
The registry reports eight outcome measures and four analyses, and it lists one secondary outcome: number of participants with adverse events. It does not report a complete statistical analysis plan, the handling of multiple comparisons, or whether adjustment for multiplicity was used. The presence of several registered measures alone does not establish that all were tested in the same way or that a particular adjustment was required.
The planning illustrations associated with the posted results use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They consider effects expressed as fractions of the observed effect. These are planning illustrations based on the observed effect, not the trial’s own design justification and not observed power. The registry does not report the trial’s sample-size justification. Because the trial is a crossover study, the equal-allocation planning assumptions should be understood as assumptions of those illustrations, not as a description of the trial’s sequence allocation or analysis.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| not stated | Ratio of Geometric Least Squares Means 98.3 | 90.7 to 106.6 | not reported |
The registry reports the sponsor’s comparison as a ratio of geometric least squares means of 98.3, with a 90% confidence interval from 90.7 to 106.6. The comparison is for the fasted and fed treatment groups. A p-value and the method used to estimate the ratio are not reported in the registry record.
No discrepancy is flagged between the sponsor analysis and the recalculation. The posted arm summaries are geometric means and geometric coefficients of variation, whereas the sponsor’s estimate is a ratio of geometric least squares means. These are not identical summaries: the latter is a comparative analysis result, and the registry does not describe its model. Any simple recalculation from posted summary statistics should therefore be treated as unadjusted and should not be mistaken for a reconstruction of the sponsor’s analysis.
The sponsor-reported estimate and confidence interval are the appropriate figures to cite as the registry’s analysis. The record does not provide enough methodological detail to independently reproduce the model-based comparison or assess all assumptions behind it. The reported result should not be extended into a formal equivalence conclusion because the registry does not state an equivalence margin or decision rule.
11. Multiplicity, Missing Data and Analysis Populations
The registry identifies maximum observed plasma concentration as the primary outcome and lists number of participants with adverse events as a secondary outcome. It reports eight outcome measures and four analyses. These entries indicate that multiple measures and analyses were registered, but they do not show how the analyses were organized into a hierarchy or whether multiplicity adjustment was used.
No statistical analysis plan, family-wise error strategy, or endpoint-specific decision threshold is reported in the registry record. The primary Cmax comparison has a reported 90% confidence interval, but the record does not state whether the interval was adjusted for multiple comparisons. A p-value is not reported for this comparison. The absence of those details limits conclusions about confirmatory testing across outcomes; it does not change the numerical result itself.
The pharmacokinetic population was defined as participants who received at least one dose and had evaluable PK profiles. The Cmax summaries list 45 participants under fasted conditions and 44 under fed conditions. Enrollment was 46. The registry does not explain the reasons for the different endpoint counts, report the amount or pattern of missing concentration data, or describe imputation or sensitivity analyses.
Because the design was a crossover, understanding the analysis population also requires knowing which participants contributed usable observations under both conditions. The record does not state the number with paired evaluable profiles or how participants with data in only one condition were handled. It would be speculative to attribute the displayed counts to withdrawal, an unusable profile, or any other specific reason.
The record also does not report a sample-size justification for the trial. Planning illustrations based on the observed effect are not a substitute for that information and are not observed power. Their stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The registry does not report how those illustrations relate to the original design decisions.
12. 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 |
|---|---|---|---|
| Apremilast - Fasted | 0 | 45 | 0.0% |
| Apremilast - Fed | 0 | 46 | 0.0% |
| Total | 0 | 46 | 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 |
|---|---|
| Apremilast - Fasted | 5 of 45 |
| Apremilast - Fed | 3 of 46 |
| Total | 7 of 46 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Apremilast - Fasted | Apremilast - Fed | Total |
|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 3 of 45 | 2 of 46 | 5 of 46 |
| Headache | Nervous system disorders | 3 of 45 | 1 of 46 | 3 of 46 |
The registry reports no serious adverse events in either treatment condition: 0 participants among 45 at risk for fasted treatment and 0 among 46 at risk for fed treatment. The total group likewise lists 0 serious adverse events among 46 at risk. No serious adverse-event terms are listed.
These are counts recorded in the registry, not evidence that serious events are impossible or that risk is absent. The study enrolled healthy adults and was designed to assess pharmacokinetics after a single dose; the registry does not provide a broader safety assessment. The deaths entries are not populated, so deaths are not reported in the registry record.
The registry separately lists other adverse events for 5 participants at risk in the fasted group and 3 in the fed group, with 7 in the total group. Those figures are distinct from the serious-event counts. The record does not provide further detail in the registry record for this analysis, so no conclusions about event types, severity beyond the serious category, or causality should be drawn from these counts alone.
General statistical context: zero observed events in a study does not establish that the underlying event probability is zero. Interpretation depends on the population, exposure, observation period, and completeness of reporting. The registry figures should therefore be read as the reported counts for this study, not as a guarantee about safety in other settings.
13. What the Result Does, and Does Not, Mean
The posted results describe the maximum observed plasma concentration of apremilast after a single 30 mg dose under fasted and fed conditions in healthy adults. The geometric mean Cmax was 339.9 ng/mL for fasted treatment and 333.9 ng/mL for fed treatment. The sponsor-reported ratio of geometric least squares means was 98.3, with a 90% confidence interval from 90.7 to 106.6.
Those values answer a narrow pharmacokinetic question. They do not measure symptom change, disease control, long-term outcomes, or the effect of repeated dosing. The population was healthy adults, and the registry does not report results for people with a health condition or for other populations. The primary outcome is a plasma concentration measure, not a clinical endpoint.
The ratio and its confidence interval convey an estimate and uncertainty, but the registry does not report an equivalence margin or a prespecified decision rule. It would therefore be unsupported to label the findings equivalent or to translate the estimate into a clinical recommendation. The absence of a reported p-value also means that a significance test cannot be described from the posted results.
The trial’s randomized crossover design compares the two conditions across two periods and sequences. However, the registry does not report the detailed analysis model, the count of participants with paired evaluable profiles, or how missing concentration data were handled. The numerical summaries should be interpreted in light of those reporting limits.
The serious adverse-event counts are zero in the listed fasted and fed groups, but the record does not establish that serious events cannot occur. The study’s scope and the available safety reporting do not support broad safety conclusions. Taken together, the record supports a description of the observed pharmacokinetic comparison and reported adverse-event counts in this study, while leaving important questions about analysis details and generalizability unanswered.
14. Why This Trial Matters Statistically
This trial illustrates how a randomized crossover design can address a focused pharmacokinetic question. Each sequence included both fed and fasted conditions, with the order reversed between sequences. General statistical context: this arrangement can make within-participant comparisons possible and can reduce the influence of stable between-participant differences, provided the analysis appropriately uses the crossover structure. The registry does not report the specific model used.
It also illustrates why the choice of summary matters. Cmax was summarized using geometric means and geometric coefficients of variation, and the comparison was reported as a ratio of geometric least squares means. These summaries express concentration comparisons on a multiplicative scale. Reading the arm means alone would not provide the same information as the sponsor’s comparative estimate and confidence interval.
The reported ratio of 98.3 and 90% confidence interval from 90.7 to 106.6 make uncertainty visible rather than presenting only a point estimate. At the same time, the registry does not state an equivalence margin or the decision rule required to interpret the comparison as a formal equivalence test. A numerical estimate and interval should not be made to answer a different inferential question than the one documented.
The record also highlights the importance of analysis-population detail. Enrollment was 46, while the posted Cmax summaries list 45 participants for fasted treatment and 44 for fed treatment. The PK population required at least one dose and evaluable profiles, but the reasons for the displayed counts and the number with paired profiles are not reported.
Finally, the study shows the boundary between a pharmacokinetic result and a clinical conclusion. The endpoint is a measured plasma concentration after a single dose, and the participants were healthy adults. The reported values inform that specific comparison; they do not, on their own, answer questions about clinical outcomes, repeated use, or other populations.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry provides limited detail about the statistical analysis. It reports the ratio of geometric least squares means and its 90% confidence interval, but does not identify the model, covariates, treatment of period and sequence, or method used to construct the interval. A p-value is not reported. The analysis cannot be fully reproduced from the registry description alone.
The crossover design makes paired participant information relevant, but the record does not report how many participants contributed evaluable profiles under both conditions. The posted Cmax summaries include 45 participants for fasted treatment and 44 for fed treatment, compared with enrollment of 46. Reasons for these counts, missing-data handling, and any sensitivity analyses are not reported in the registry record.
The registry describes two treatment periods and randomized sequences, but does not report the interval between periods or any washout details. It also does not state whether period or carryover effects were assessed. These are reporting gaps; they do not show that such procedures or assessments were absent.
The endpoint is Cmax after a single 30 mg dose, with sampling through 48 hours after dosing. It does not describe all aspects of drug exposure or clinical outcomes. The study population was healthy adults, so the posted results do not directly describe other populations or repeated-dose use.
The registry does not report an equivalence margin, a protocol-based sample-size justification, or a complete multiplicity strategy. Planning illustrations based on observed effects are not the original design justification and are not observed power. Finally, the serious adverse-event counts are zero in the listed groups, but the registry record does not provide populated death counts or enough detail to make broad safety conclusions.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Effect of Food on the Pharmacokinetics of Apremilast (CC-10004) in Healthy Adults — NCT01634178.
- Registry record last updated 2021-04-21; status last verified 2021-03.
- Results first posted 2021-04-21.
- 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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19. Record Summary
NCT01634178 is a completed Phase 1, randomized, open-label, two-period, two-sequence crossover study sponsored by Amgen. It enrolled 46 healthy adults and examined a single 30 mg dose of apremilast under fasted and fed conditions.
The primary endpoint was maximum observed plasma concentration, measured in ng/mL. The posted geometric means were 339.9 for fasted treatment and 333.9 for fed treatment. The sponsor-reported ratio of geometric least squares means was 98.3, with a 90% confidence interval from 90.7 to 106.6. A p-value and the analysis method are not reported in the registry record.
The pharmacokinetic population required at least one dose and evaluable profiles. Serious adverse-event counts were 0 in the fasted and fed groups. The record does not report the detailed analysis model, missing-data methods, equivalence margin, or trial sample-size justification.