A Drug-Drug Interaction Study Between Fenofibric Acid and Efavirenz: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Drug-Drug Interaction Study Between Fenofibric Acid and Efavirenz (NCT01472380), a non-randomized phase 1 study. The primary outcome is Pharmacokinetics: Maximum Plasma Concentration (Cmax).

2. Clinical Question

The biological rationale recorded for the study is that efavirenz is predominantly metabolized by CYP2B6 and fenofibric acid is an inhibitor of CYP2B6. That rationale motivates examining drug exposure; it does not establish what effect was observed in this study.

The stated comparison concerns pharmacokinetics in healthy subjects, rather than a clinical outcome in people being treated for a condition. The registry lists a fenofibric-acid-alone group in the safety information, but does not provide a corresponding dosing description in the arm descriptions. Further details of the exposure sequence and any within-participant analysis are not reported in the registry record.

3. Trial Design

This completed Phase 1 study was open-label, non-randomized, and classified as a single-group study. The registry lists 30 enrolled healthy subjects. The planned focus was the effect of steady-state fenofibric acid on the pharmacokinetics of single-dose efavirenz.

The arm descriptions state that efavirenz 600mg was taken by mouth on Day 1, and that oral efavirenz 600 mg and fenofibric acid 105 mg were co-administered on Day 31. The registry’s safety information also lists a fenofibric-acid-alone group. Details of that group’s dosing schedule are not reported in the registry record.

Because allocation was non-randomized and the record classifies the study as single-group, the displayed exposure groups should not be read as randomized, independent treatment arms. The registry record itself flags that the arms are not a like-for-like control comparison. It does not give enough detail to establish exactly how each participant contributed to each exposure group or how the planned comparison was analyzed.

The primary pharmacokinetic measure was Cmax, with serial blood sampling immediately before dosing on Days 1 and 31 and at listed post-dose times through 120 hours. The registry lists three outcome measures and no analysis entries. It does not report a protocol-based sample-size justification, randomization procedure, masking procedure beyond none, interim analyses, or a detailed statistical analysis plan.

The study status is completed. Its start and primary completion are recorded as 2011-11 and 2011-12. These design details describe what the registry record reports; they do not establish whether all planned analyses were completed or posted.

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.

Efavirenz Alone

Reasons for not completing this period:

Fenofibric Acid (FFA) Alone

1 Day Period Between Dosing

Reasons for not completing this period:

Efavirenz and FFA

Analysis population for the primary outcome, as defined in the registry: 28 of 30 subjects completed the entire study and had sufficient data to calculate at minimum the maximum concentration (Cmax)for efavirenz.

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 Pharmacokinetics: Maximum Plasma Concentration (Cmax), measured over serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 31 and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, 96, and 120 hours after dose administration.

The primary endpoint is efavirenz maximum plasma concentration, or Cmax, measured in ug/mL. Cmax is the peak concentration observed in plasma after a dose. The registry describes it as the maximum or peak concentration that efavirenz reaches in plasma and specifies the mean and standard deviation as the summary measures.

In general, Cmax is used in pharmacokinetic studies because it summarizes the observed peak exposure after dosing. Comparing Cmax across exposure conditions can help describe whether the peak concentration differs when another drug is present. This is a general explanation of the measure, not a claim about the result of this study.

Blood samples were scheduled immediately before dosing on Days 1 and 31, followed by serial collection at the times listed in the registry through 120 hours after dose administration. The registry notes that 28 of 30 subjects completed the entire study and had sufficient data to calculate at minimum Cmax for efavirenz.

The registry record does not report the group means, standard deviations, an estimated difference or ratio, or a confidence interval for Cmax. It therefore does not allow the reader to assess the magnitude or precision of the primary endpoint comparison from the posted record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry names Cmax as the primary pharmacokinetic endpoint and specifies a mean with standard deviation. These are descriptive summaries of a continuous measurement. A mean describes the central level of the observations, while a standard deviation describes their spread around that mean. These summaries are not reported numerically in the registry record, so they cannot be used to compare exposure conditions.

In general, a comparison of means can be expressed as a difference or another contrast, depending on the scientific question and analysis plan. The record does not report the contrast used for Cmax, an estimate, a confidence interval, or a test statistic. It also does not report the statistical model or whether the analysis accounted for repeated measurements or within-participant observations. Those details should not be inferred from the single-group classification or the dosing days alone.

What does the endpoint measure?

Cmax is the highest measured plasma concentration after dosing. The registry scheduled serial blood samples before dosing and at multiple post-dose times, with collection continuing through 120 hours. Sampling across time is important because an observed peak depends on when samples are collected. In general, if the true peak falls between collection times, the maximum measured value may not exactly equal the underlying peak. The registry does not describe any method for estimating a peak between sampled times.

How should uncertainty be read?

General statistical interpretation separates the estimated effect from its uncertainty. A confidence interval, when reported, gives a range of values consistent with the data under the specified method and assumptions. A narrow interval indicates greater precision than a wide interval, while neither interval alone establishes clinical importance. The registry does not report a confidence interval for the primary endpoint, so precision cannot be assessed from this record.

A p-value, if reported, would address compatibility of the observed data with a specified null model; it would not state the probability that the null hypothesis is true or measure the size of an effect. No analysis entries are listed, and no p-value for Cmax is reported in the registry record. Therefore, there is no basis to characterize statistical significance.

What does the design imply?

The study is described as non-randomized and single-group, and the registry warns that the groups are not a like-for-like control comparison. In general, random allocation can help balance measured and unmeasured factors between groups. Without random allocation, differences between exposure conditions can be affected by design features or other changes over time. The registry descriptions place the efavirenz-alone dose on Day 1 and the co-administration on Day 31, but do not report enough detail to assess the full sequence, possible period effects, or the analysis of repeated observations.

The open-label designation means masking is listed as none. For an objectively measured concentration, expectations are less directly involved in measurement than for a subjective outcome, but open-label status still describes the study’s conduct and should not be silently treated as blinded. The record does not describe laboratory procedures or any safeguards against measurement bias.

How should the planning illustration be understood?

General sample-size calculations estimate how many observations might be needed under specified assumptions to detect a chosen effect with a chosen error rate and power. The planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of the observed effect. It is explicitly a planning illustration based on the observed effect, not the trial’s own design. The registry record does not report the trial’s sample-size justification.

Such calculations depend on their assumptions, including the effect used and the variability expected. They are not a retrospective measure of whether a study had adequate power, and they should not be presented as observed power. The stated convention is that non-time-to-event sample-size illustrations give participants per arm; there are no time-to-event outcomes. Since the numerical planning outputs are not in the registry record, this discussion does not characterize their values.

The registry lists three outcome measures but no analysis entries. The statistical analysis plan, treatment of multiplicity, missing-data methods, model diagnostics, and any adjustments are not reported in the registry record. General statistical methods cannot fill those gaps; the interpretation should remain limited to what the posted record documents.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Efavirenz Alone", "Efavirenz With Fenofibric Acid")
n   <- c(28, 28)
m   <- c(2.62, 2.63)
sp  <- c(0.57, 0.55)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Efavirenz Alone  28  2.620  0.570  2.399  2.841
CARM  Efavirenz With Fenofibric Acid  28  2.630  0.550  2.417  2.843

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, while the record lists no analysis entries. It does not state which outcomes, beyond the named primary Cmax endpoint, were included in any completed statistical analysis, or whether multiple outcomes or comparisons were adjusted for. Multiplicity refers, in general, to the increased chance of misleading findings when several hypotheses are tested. Whether and how that issue was addressed is not reported in the registry record.

The primary endpoint population description states that 28 of 30 subjects completed the entire study and had sufficient data to calculate at minimum Cmax for efavirenz. The record does not explain why the other subjects did not meet that description, whether they contributed to other outcomes, or how missing observations were treated. No imputation procedure, sensitivity analysis, or missing-data assumption is reported.

The record does not specify an intention-to-treat population, a per-protocol population, or another formal analysis population. It also does not report whether the Cmax summary was calculated only among subjects with available measurements or according to another rule. These omissions make it difficult to assess how closely the analyzed population may correspond to the enrolled population.

In general, missing-data methods rely on assumptions about why measurements are unavailable. Different assumptions can lead to different estimates, so transparent reporting of participant flow and analysis populations is useful. The available registry description identifies the number with sufficient Cmax data but does not provide those methodological details.

12. 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 lists serious adverse events as 0 in the efavirenz-alone group, among 30 at risk; 0 in the fenofibric-acid-alone group, among 29 at risk; and 0 in the efavirenz-with-fenofibric-acid group, among 28 at risk. These are the recorded serious-event figures for the listed groups. They should not be read as proof that no serious event could occur, particularly because the study enrolled a limited number of healthy subjects.

The registry also lists other adverse events affecting 19 of 30 in the efavirenz-alone group, 2 of 29 in the fenofibric-acid-alone group, and 15 of 28 in the combination group. These are group-specific counts, not a randomized comparison. Because the record describes a non-randomized, single-group study and does not establish like-for-like control groups, the counts alone do not establish that one exposure caused more or fewer events than another.

Deaths are not reported in the registry record. The record does not provide the adverse-event terms beyond indicating that no top serious-event terms are listed. These figures are a description of the posted safety information, not an assessment of an individual’s risk.

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

The registry record establishes that a completed Phase 1 study was designed to examine efavirenz pharmacokinetics when efavirenz was taken alone and when it was co-administered with fenofibric acid. It identifies Cmax as the primary endpoint and describes the biological rationale involving CYP2B6. It also reports the study’s open-label, non-randomized, single-group design and the number of subjects with sufficient data for at least the primary measure.

The record does not report numerical primary-endpoint results. Consequently, it cannot show whether Cmax was higher, lower, or similar across the described exposure conditions, and it cannot show the magnitude or precision of a comparison. No conclusion about statistical significance is available from the listed record.

Even when numerical results are available, a pharmacokinetic measure is not itself a clinical outcome. In general, concentration data describe drug exposure; translating such data into implications for clinical outcomes requires evidence and context beyond a peak concentration alone. This study’s stated population was healthy subjects, and the registry does not report clinical outcomes in patients being treated for a condition.

The safety counts are also descriptive. They report no serious adverse events in the listed groups and give counts for other adverse events, but the non-randomized design and lack of a like-for-like control comparison limit comparative interpretation. The registry record does not report deaths.

Overall, the posted information supports an account of the question, design, endpoint, and some safety counts. It does not support a quantitative statement about the primary pharmacokinetic effect. Any stronger interpretation would require results and analysis details not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why a clearly stated pharmacokinetic question and a reported numerical result are both needed for statistical interpretation. The registry gives a specific endpoint, efavirenz Cmax, and a rationale for examining it with fenofibric acid. But without endpoint estimates and measures of uncertainty, the reader cannot determine what the observed comparison was or how precisely it was measured.

It also highlights the importance of interpreting study structure before comparing groups. The registry identifies the design as non-randomized and single-group and explicitly cautions that the arms are not a like-for-like control comparison. Group labels by themselves do not make exposure groups equivalent to independently randomized treatment arms. A clear account of participant-level exposure and analysis would help readers understand what contrast the data can support.

The record further distinguishes enrollment from availability of endpoint data: 30 subjects were enrolled, while 28 of 30 completed the entire study and had sufficient data to calculate at minimum Cmax. Reporting why measurements are unavailable and how the analysis handled them is important for judging the evidence.

Finally, the planning calculations on the page should be kept separate from the study’s original design and results. A sample-size illustration based on an observed effect can help explore planning assumptions, but it is not a substitute for a reported effect estimate, a confidence interval, or a documented sample-size justification. The registry record does not report the trial’s own design rationale or detailed statistical plan.

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 principal limitation for interpreting this record is that it does not report numerical results for the primary Cmax endpoint. It therefore lacks the estimate and uncertainty needed to describe the observed pharmacokinetic comparison. The registry also lists no analysis entries, so the methods used to derive or compare endpoint summaries are not available.

The design is open-label, non-randomized, and single-group. The record cautions that the exposure groups are not a like-for-like control comparison. It gives the efavirenz-alone and combination dosing days, but does not report enough detail to reconstruct the full participant-level sequence or determine how time and repeated observations were handled.

The registry’s safety listing includes a fenofibric-acid-alone group, but its dosing description is not included in the arm descriptions. This limits interpretation of that group’s role and exposure. The record also does not report the reasons that 28 of 30 subjects, rather than all enrolled subjects, completed the study with sufficient data to calculate at minimum Cmax.

Further details not reported in the registry record include the statistical analysis plan, missing-data methods, analysis populations, multiplicity handling, protocol-based sample-size justification, interim analyses, and any model assumptions or diagnostics. These gaps mean that this page can describe the posted design and counts, but cannot independently assess the primary result or the robustness of an analysis that is not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Drug-Drug Interaction Study Between Fenofibric Acid and Efavirenz — NCT01472380.
• Registry record last updated 2012-08-01; status last verified 2012-07.
• Results first posted 2012-07-23.
• 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.

19. Record Summary

This completed Phase 1 study examined the effect of steady-state fenofibric acid on the pharmacokinetics of single-dose efavirenz in healthy subjects. It was open-label, non-randomized, and classified as a single-group study, with 30 subjects enrolled.

The primary endpoint was mean efavirenz Cmax in ug/mL, summarized with standard deviation. The registry describes efavirenz 600mg alone on Day 1 and co-administration of efavirenz 600 mg with fenofibric acid 105 mg on Day 31. It reports that 28 of 30 subjects completed the entire study and had sufficient data to calculate at minimum Cmax.

Numerical primary results, analysis entries, and a detailed statistical plan are not reported in the registry record. The posted safety information lists no serious adverse events in the three exposure groups and includes counts for other adverse events.