Analysis of Crushed and Whole Tablet Genvoya: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Analysis of Crushed and Whole Tablet Genvoya (NCT03717129), a non-randomized phase 4 study. The primary outcome is Area Under the Curve From 0 to Infinity (AUC0-∞) for EVG.

2. Clinical Question

In general, a pharmacokinetic bioequivalence question asks whether drug exposure after one formulation is sufficiently similar to exposure after another, according to prespecified criteria. The endpoint listed for this study is EVG AUC0-∞, measured in ng*h/mL, with a 72-hour timeframe. The record also lists secondary outcomes involving peak concentration and half-life measures for EVG, COBI, FTC, and TFV.

The stated question is about formulation and exposure following single doses in healthy volunteers. It is not a question about clinical effectiveness, long-term use, or outcomes in people with a medical condition. The registry record does not report the criteria used to declare bioequivalence, or numerical endpoint results with which to assess the question.

3. Trial Design

This completed phase 4 study, sponsored by Johns Hopkins University, enrolled 12 healthy volunteers. Its registry title is “Analysis of Crushed and Whole Tablet Genvoya.” The official title describes bioequivalence of crushed and whole Genvoya tablets, containing elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide fumarate. The recorded study dates are 2019-04-15 for the start and 2021-11-01 for primary completion.

The design is recorded as a nonrandomized crossover with no masking. According to the study summary, participants first received a directly observed single dose of the whole tablet, with semi-intensive pharmacokinetic serum sampling at time points following the dose. After a washout period of seven days, participants then received a directly observed single dose of the crushed tablet, followed by serum sampling. This is a sequential order: whole tablet first, crushed tablet second.

In general, a crossover design measures different conditions in the same participants. This can support a within-participant comparison, because each participant contributes observations under both conditions. It does not make the sequence randomized. In this study, the listed order means treatment condition and period are linked: the whole-tablet observation occurs first and the crushed-tablet observation occurs second. Order or period effects therefore matter when interpreting a comparison. The registry record does not report an analysis of such effects.

The listed enrollment is 12; the record does not describe a separate control group receiving neither formulation. The registry also does not report the allocation procedure beyond identifying it as nonrandomized, or additional details about adherence, participant flow, or reasons for any missing observations.

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: This is a cross-over study where participants acted as their own controls. All participants received Genvoya oral first, and then crossed over to Genvoya crushed after a 2-week washout period.

Genvoya Oral Dose (1 Week)

Washout (2 Weeks)

Genvoya Crushed Dose (1 Week)

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 Curve From 0 to Infinity (AUC0-∞) for EVG, measured over 72 hours.

The primary endpoint is the area under the concentration-time curve from 0 to infinity for elvitegravir (EVG), reported in ng*h/mL, with a 72-hour timeframe. AUC is a measure of exposure: in general, it represents the area accumulated under a drug concentration-versus-time profile. AUC0-∞ refers to exposure from dosing onward, including the portion extrapolated beyond the observed sampling period when the method calls for that extrapolation. The registry record does not report the calculation details used for this endpoint.

Exposure is relevant to a bioequivalence question because two formulations may be compared by how much drug reaches the circulation over time. The primary endpoint is a mean of a continuous measure, and the registry identifies standard deviation as its dispersion measure. Those summaries describe a group’s average exposure and the variability among observations, but they do not by themselves establish whether two formulations meet a bioequivalence criterion.

To interpret a bioequivalence analysis, readers generally need the comparison estimate and its uncertainty, along with the prespecified acceptance bounds and analysis method. These are not reported in the registry record. No primary endpoint values, comparison estimate, or confidence interval are reported, so the endpoint’s observed magnitude and precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The listed primary outcome is continuous: it is a mean EVG AUC0-∞, with standard deviation as the stated measure of dispersion. In general, the mean describes the central level of a continuous measure, while the standard deviation describes how spread out individual observations are around that mean. Neither measure alone provides the uncertainty of a treatment comparison. To assess uncertainty in the difference or ratio between formulations, an analysis would need to account for the study design and report an estimate with an interval or another suitable uncertainty measure. The registry record does not report those analyses.

Why does crossover structure matter?

In a crossover study, participants receive more than one condition, so observations from the same participant are related. General statistical methods for crossover data account for that within-participant relationship rather than treating all observations as independent. This can make a paired comparison useful: stable participant characteristics are shared across the two measurements. But the registry’s described sequence is fixed, with the whole tablet first and crushed tablet after a seven-day washout. Because condition and period move together in that order, a difference between measurements could reflect formulation, period, or other order-related influences. The registry record does not report a model, a period-effect assessment, or a carryover assessment.

What would a bioequivalence estimate communicate?

In general, bioequivalence analyses commonly compare exposure measures on a relative scale, and the analysis may use transformations suited to positive, skewed pharmacokinetic measurements. The particular scale, transformation, and model used for this study are not reported in the registry record. A confidence interval for the comparison would communicate its statistical precision. A bioequivalence decision would then depend on whether the interval satisfies prespecified acceptance bounds. Neither those bounds nor an interval estimate is reported, so no decision can be independently evaluated from the registry information.

These general concepts do not describe confirmed procedures for this study. The record specifies the endpoint and design, but it does not report the analysis plan, the statistical model, assumptions, diagnostics, or a test result. It also does not report a protocol-based sample-size justification. The planning assumptions listed for illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects described as stated fractions of the observed effect. Such illustrations are planning calculations, not observed power. The numerical planning results and the observed endpoint effect are not reported in the registry record. The listed assumptions should not be mistaken for confirmation that the trial’s primary analysis used that approach.

How should precision be read?

In general, an estimate is more informative when accompanied by a measure of uncertainty. A confidence interval gives a range of values that are compatible with the data under the specified model and procedure. It does not guarantee that the true value lies in the interval, and it does not correct for design limitations, missing observations, or unreported analytical choices. For this study, no primary estimate or confidence interval is reported. Thus neither statistical precision nor the range of plausible exposure contrasts can be described using the registry record.

The record lists standard deviation for the primary measure, but does not give a standard deviation value. It also does not provide individual-level observations or summary values by formulation. Without those quantities, no independent recalculation of the EVG comparison is possible. There are no reported analyses to compare with a recalculation, and no sponsor analysis result is stated in the registry record.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means that observed variability exceeds what a chosen model expects. It can lead to uncertainty estimates that are too small if the model does not account for the extra variability. That concept is not directly the primary endpoint issue in this trial, because the listed endpoint is a continuous pharmacokinetic measure rather than a count. The registry does not report a count-outcome analysis or a model for such data. For a continuous exposure measure, the relevant general concerns include the distribution of measurements, influential observations, model assumptions, and the paired structure; the record does not report how these were evaluated.

How do the secondary outcomes fit?

The registry names secondary measures including EVG, FTC, and TFV Cmax, and half-life measures for EVG, COBI, FTC, and TFV. Cmax generally refers to a peak concentration measure; half-life describes the time course of decline under a defined pharmacokinetic model. These are general meanings, not claims about the calculations used in this study. The record reports 11 outcome measures overall but does not report the full set of numerical results, analysis methods, or which outcomes were included in any particular analysis. The number of analyses is recorded as zero.

Because the primary endpoint and multiple secondary measures are listed, multiplicity is a potential interpretive issue in general. When many outcomes are tested, the chance of at least one apparently notable result can increase, depending on the testing strategy. A prespecified hierarchy or adjustment may address this issue, but the statistical plan and any multiplicity procedure are not reported in the registry record. With no outcome analyses reported, it is not possible to determine whether multiplicity was addressed or how it would affect interpretation.

All of these statistical principles help frame what would be needed to interpret a crossover bioequivalence analysis. They do not fill in missing trial results. The registry record documents the endpoint definition, design sequence, and enrollment, but does not report a fitted model, an estimate, a confidence interval, or the assumptions used in an analysis.

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("Genvoya Oral Dose", "Genvoya Crushed Dose")
n   <- c(12, 12)
m   <- c(24219, 26948)
sp  <- c(6074, 5955)
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  Genvoya Oral Dose  12  24219.000  6074.000  20359.765  28078.235
CARM  Genvoya Crushed Dose  12  26948.000  5955.000  23164.374  30731.626

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 11 outcome measures, including the primary EVG AUC0-∞ measure and secondary pharmacokinetic outcomes. It records no analyses. A multiplicity strategy, such as a prespecified hierarchy or adjustment across outcomes, is not reported in the registry record. In general, when several outcomes are assessed, the interpretation of isolated findings depends partly on whether the analysis plan accounted for the number and relationship of those assessments. No outcome results are reported to evaluate under such a strategy.

Missing-data procedures and analysis populations are also not reported in the registry record. It does not state how incomplete pharmacokinetic sampling, missing endpoint values, or participant withdrawals would be handled, nor does it describe which participants were included in each analysis. Enrollment of 12 volunteers does not establish that all 12 contributed complete data to every endpoint.

The study summary describes a fixed sequence of whole tablet followed by crushed tablet after a seven-day washout, but the registry does not report details of the analysis population, model specification, or sensitivity analyses. It is therefore not possible to determine how the reported design was reflected in any statistical analysis. The protocol’s statistical analysis plan and missing-data assumptions are not reported in the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists two exposure groups: Genvoya Oral Dose and Genvoya Crushed Dose. For each, 12 participants are listed as at risk for serious adverse events and 0 as affected; for other adverse events, 12 are listed as at risk and 0 as affected. Deaths are listed as 0 in each group. These are counts recorded for each exposure group, not a comparison demonstrating a difference in safety between formulations.

In general, zero recorded events does not establish that the underlying risk is zero. Interpretation depends on how events were defined, collected, and followed, as well as the amount of observation. The registry record does not report detailed safety ascertainment methods, event descriptions, or follow-up completeness. The study summary describes single-dose administration with pharmacokinetic sampling, but the registry does not give a separate safety follow-up description. The figures should therefore be read as the adverse-event counts in the record, not as proof that no events occurred beyond those recorded.

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

The record establishes that a completed phase 4 crossover study enrolled 12 healthy volunteers to examine a whole Genvoya tablet followed by a crushed tablet, with a seven-day washout between doses. Its primary question concerns EVG exposure measured by AUC0-∞ over a 72-hour timeframe. The design and endpoint make clear what comparison the study was intended to address.

The record does not report the primary endpoint values, a comparison estimate, a confidence interval, or an analysis conclusion. It therefore does not show whether exposure differed in a particular direction or by what amount, and does not establish whether the prespecified standard for bioequivalence was met. The acceptance criteria and analysis plan are not reported in the registry record. Absence of results in the registry should not be interpreted as evidence that the formulations are equivalent or different.

The findings, if reported elsewhere, would pertain to the stated single-dose study in healthy volunteers. The registry information does not establish what would happen with repeated dosing, in people with a medical condition, or for clinical outcomes. Those questions are outside the outcomes described in this record.

The safety counts are also limited: the record lists zero serious adverse events, zero other adverse events, and zero deaths in each exposure group, with 12 at risk in each. These counts describe recorded events, not a general guarantee about safety. Overall, the registry record supports a description of the research question and design, but not a conclusion about the numerical pharmacokinetic comparison or its precision.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between a trial’s question and the evidence needed to answer it. The registry specifies an exposure endpoint and a comparison of two formulations, but does not report the numerical outcome analysis. A design description can clarify what researchers intended to estimate; it cannot replace the estimate, its uncertainty, or the decision rule used to interpret it.

The crossover format also makes the structure of the data central to analysis. Measurements from the same participant are generally related, and the sequence in this study is described as whole tablet first and crushed tablet second. A statistical interpretation should therefore take account of pairing and consider whether period or order effects could matter. The registry record does not describe the analysis used to address these considerations.

Bioequivalence is a question of precision as well as similarity. General assessment requires comparing an estimate and its uncertainty with prespecified bounds. A statement that a study aimed to determine bioequivalence is not itself a result, and a sample-size illustration is not observed power. Without the endpoint comparison and analysis details, the statistical evidence cannot be judged from the registry record.

The study also demonstrates why clear reporting of analysis populations, missing-data handling, and multiplicity procedures matters. The registry lists multiple outcomes, but does not report analyses or these methodological details. For readers assessing a pharmacokinetic study, the design, endpoint, result, uncertainty, and analysis choices need to be considered together.

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 record has several study-specific limitations for statistical interpretation. It describes a nonrandomized, unmasked crossover in which participants received the whole tablet first and the crushed tablet after a seven-day washout. With a fixed order, formulation and study period are linked. The record does not report whether period effects or carryover were assessed, or how they were handled analytically.

The enrollment is 12 healthy volunteers, but the registry does not report the protocol’s sample-size justification or the number with complete data for each outcome. It does not give participant flow, missing-data methods, analysis populations, endpoint estimates, or measures of precision. The primary endpoint is identified, but acceptance bounds and the statistical analysis plan are not reported in the registry record.

The record lists 11 outcome measures and no analyses. It therefore does not permit assessment of multiplicity, outcome-specific results, or whether the primary endpoint was analyzed as planned. The described single-dose study in healthy volunteers also limits the scope of what the design addresses; the record does not report repeated-dose or clinical outcome results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Analysis of Crushed and Whole Tablet Genvoya — NCT03717129.
• Registry record last updated 2023-01-31; status last verified 2023-01.
• Results first posted 2023-01-31.
• 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

NCT03717129 is a completed phase 4 study sponsored by Johns Hopkins University. It enrolled 12 healthy volunteers and is recorded as a nonrandomized, unmasked crossover. Participants received a single whole Genvoya tablet first, then a crushed tablet after a seven-day washout, with pharmacokinetic serum sampling described after each dose.

The primary endpoint is EVG AUC0-∞ in ng*h/mL, with a 72-hour timeframe. The registry lists 11 outcome measures and no analyses. It reports zero serious adverse events, zero other adverse events, and zero deaths in each exposure group, with 12 at risk per group. Numerical outcome results, analysis details, and bioequivalence criteria are not reported in the registry record.