An Interaction Study to Assess Drug Levels in Fasting Healthy Adult Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Interaction Study to Assess Drug Levels in Fasting Healthy Adult Subjects (NCT00802074), a randomized na study. The primary outcome is Cmin/Cmax: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID..

2. Clinical Question

This is a pharmacokinetic interaction question, rather than a question about clinical efficacy. APV is identified in the registry as the active ingredient or metabolite of FPV. The planned concentration measurements were intended to characterize drug exposure under the different combinations. The record describes randomized assignment and an open-label design, but does not provide outcome estimates that would establish the direction or precision of any interaction.

3. Trial Design

The registry describes a randomized, open-label drug-interaction study in healthy adults under fasting conditions. The title calls the study six-period, whereas the brief summary describes a six-arm, three-period study, and the group descriptions list Period 1, Period 2, and Period 3. This difference in the record’s descriptions is not explained. Masking is listed as none, and the model is listed as factorial.

The arm descriptions pair groups with the same FPV-based regimens in different orders. Groups A and B include FPV 1400mg BID with and without RTG 400mg BID. Groups C and D include FPV 700mg BID with RTV 100mg BID, with and without RTG 400mg BID. Groups E and F include FPV 1400mg QD with RTV 100mg QD, with and without RTG 400mg BID. Each group description also lists RTG 400mg BID in Period 1. The primary outcome description says that data from the corresponding groups were collated for assessment.

There are differences in dosing descriptions across registry text. The official title describes a 14-day RTG regimen and 14-day FPV-based regimens, while the brief summary describes a 7-day RTG-alone regimen and 14-day combination regimens. The record does not explain this variation. Its primary outcome timeframe names Day 14 of the FPV-based regimens.

The registry enrollment field lists 45, while the brief summary describes 48 healthy adults. These figures are not reconciled. The study is listed as completed, with a start in 2008-12 and primary completion in 2009-03. No allocation sequence details, washout information, or further conduct details are reported in the registry record.

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:

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Cmin/Cmax: Fasting Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID., measured over Day 14 of the FPV 1400mg BID, FPV 1400mg/RAL 400mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/RAL 400mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus RAL 400mg BID regimens.

The primary outcome concerns steady-state plasma APV pharmacokinetics during FPV regimens, with and without concurrent RTG. The outcome title emphasizes minimum concentration (Cmin) and maximum concentration (Cmax). The accompanying description also names area under the plasma concentration-time curve (AUC) and oral clearance (CL/F). Concentrations were to be assessed from blood samples collected at specified times during the BID and QD regimens. The endpoint timeframe is Day 14 of the listed regimens.

In general, Cmin describes the lowest measured concentration over a dosing interval, while Cmax describes the highest. AUC reflects drug exposure across the sampling interval, and clearance describes the apparent rate at which drug is removed from the body relative to exposure. These are general pharmacokinetic interpretations. Together, such measures can characterize different aspects of exposure and help assess whether coadministration is associated with a change in drug concentrations. They do not, by themselves, establish a clinical benefit or harm.

The registry specifies the unit as ng/mL and the summary measure as mean, with a 90% confidence interval. It does not provide numerical estimates, confidence limits, or a defined primary contrast among the regimens. Although the title focuses on Cmin and Cmax, the description includes additional measures; the record does not clarify how these measures were prioritized or how results were to be combined into an overall conclusion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, open-label study with a factorial model, but it does not report the statistical methods used to analyze the primary outcome. In particular, the analysis model, treatment-contrast definitions, handling of repeated measurements, and adjustment factors are not reported in the registry record. The description of how regimen data were collated across groups is not a substitute for an analysis plan.

What does a 90% confidence interval communicate?

In general, a confidence interval expresses uncertainty about an estimated quantity under the assumptions of the statistical procedure. It provides a range of values compatible with the data and method, rather than a guarantee that the true value lies within that particular interval. Its width reflects precision: intervals that are wider indicate greater uncertainty than narrower intervals. The registry names a 90% confidence interval for the mean, but no interval bounds or associated estimates are reported. Therefore, the precision of the APV measurements and contrasts cannot be judged.

Why distinguish peak, trough, and overall exposure?

As general pharmacokinetic context, Cmax characterizes the peak concentration, while Cmin characterizes the minimum concentration over the relevant dosing interval. AUC summarizes exposure across a period of concentration sampling, and CL/F is a measure of apparent oral clearance. These measures address related but different features of drug disposition. A change in one measure cannot be assumed to imply a particular change in another. The outcome description lists all of these measures, but does not report their results or explain whether one was the principal basis for interpretation.

What is important about the design?

The group descriptions place regimens in different orders and state that corresponding groups were combined for PK assessment. In general, when observations are collected from the same participant under different regimens, the analysis may need to account for within-participant dependence and period or sequence effects. That is general methodological context, not a description of the analysis used in this study. The registry record does not say whether the same participants contributed measurements under each regimen, how order effects were assessed, or how the analysis handled period effects.

The record’s wording is not fully consistent about the number of periods: the title uses six-period, while the brief summary and arm descriptions refer to three periods. It also differs on the length of the initial RTG-alone regimen. Because the registry does not resolve those descriptions, it is not possible to give a more specific account of the analysis structure from this record.

How should the analysis status be read?

The registry lists seven outcome measures and zero analyses. This means the record does not contain reported analysis results for the primary pharmacokinetic outcome. It does not establish that no analysis was conducted outside the registry; any such analysis is not reported in the registry record. There are no reported estimates, standard errors, confidence limits, test statistics, or p-values to interpret.

The record also does not report how missing pharmacokinetic samples were handled, what analysis population was used, or whether participants with incomplete periods were included. Those details matter in general because missing concentration measurements or incomplete participation can affect which observations contribute to an estimate and the assumptions needed to interpret it. No missing-data method can be inferred from the listed sampling schedule.

What can the sample-size illustrations establish?

Any sample-size figures associated with the posted results are planning illustrations based on the observed effect, not evidence of observed power. The stated assumptions for those illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. Such calculations are hypothetical planning scenarios. They do not show that the trial was designed with those assumptions, and the registry does not report a sample-size justification. No planning value should be interpreted as the number actually analyzed or as proof that the study could detect a particular effect.

In general, a planning calculation depends on the effect size and assumptions used. If the effect used for an illustration is itself estimated from trial results, the calculation remains a planning exercise and is not observed power. The registry does not report the primary outcome estimates needed to independently assess those assumptions, nor does it provide the trial’s own design rationale.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description lists several pharmacokinetic measures: Cmin, Cmax, AUC, and CL/F. The outcome title emphasizes Cmin and Cmax, but the registry does not state how these measures were prioritized, whether one was designated as the decisive endpoint, or whether any multiplicity adjustment was planned. The number of outcome measures is listed as seven, but that count does not describe a testing hierarchy or correction procedure. Multiplicity handling is not reported in the registry record.

The record does not report an analysis plan, prespecified contrasts, or whether the comparisons across the three FPV-based regimens were intended to be treated as separate confirmatory questions. It also does not say whether the analysis would account for the different regimen orders or repeated measurements. These omissions prevent assessment of how statistical uncertainty across the set of measures and comparisons was managed.

Missing-data handling is not reported in the registry record. Although the description specifies blood-sampling time points, it does not state how missed samples, incomplete concentration profiles, or withdrawals were handled. The analysis population is also not reported: there is no stated definition of which randomized participants, completed periods, or available samples contributed to each outcome estimate. The enrollment field and brief summary list different participant counts, without a reconciliation or outcome-specific denominators.

The record contains no analysis results for the primary outcome. It therefore gives no basis for determining whether analyses were adjusted, whether all planned measures were reported, or whether missingness affected the estimates. These are limitations of the registry reporting; they do not establish what methods may have been used elsewhere.

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’s serious-adverse-event entries list zero affected participants in Groups A, B, C, D, E, and F. The corresponding numbers at risk are 7, 7, 6, 7, 7, and 7, respectively. No serious adverse-event terms are listed. The death entries are null, so deaths are not reported in the registry record; a null entry should not be read as a confirmed count of zero.

These are group-level descriptive entries. They do not provide a statistical comparison among regimens, an estimate of relative risk, or information about the timing or duration of events within dosing periods. The registry also lists participants with other adverse events, but those entries do not alter the interpretation of the serious-event figures.

In general, a zero count in a group does not demonstrate that the underlying risk is zero. The registry entries should be read as the adverse-event information recorded for this study, with the listed group denominators, rather than as evidence that serious events cannot occur. A fuller account of event definitions, collection procedures, and exposure time is not reported in the registry record.

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

The record describes a randomized, open-label pharmacokinetic study intended to assess APV exposure during FPV-based regimens with and without concurrent RTG. It identifies Cmin and Cmax in the primary outcome title and also lists AUC and CL/F in the outcome description. This establishes the scientific focus of the registered study, but does not reveal what the measurements showed.

No numerical primary-outcome estimates, confidence intervals, or analyses are reported in the registry record. The available information therefore cannot establish whether APV concentrations changed with concurrent RTG, how large any change was, or how precisely it was estimated. It also cannot establish that the regimens were equivalent or that no interaction occurred. Absence of reported estimates is not evidence that the comparison found no difference.

The study population was described as healthy and fasting, and the registry’s brief summary describes participants as HIV-negative. The results, even if available, would pertain to the study conditions and population represented in the record. The registry does not provide evidence about clinical outcomes or establish how the pharmacokinetic findings would apply outside those conditions.

The safety record lists zero participants affected by serious adverse events in each group, but the death entries are null and the event information is limited. These entries cannot establish that a regimen is free of risk. Similarly, the completed status does not substitute for results or explain whether every planned measure was analyzed.

The appropriate interpretation is therefore narrow: the registry records a planned comparison of APV pharmacokinetics across FPV-based regimens with and without RTG, but it does not report the numerical evidence needed to answer that comparison. It supports describing the question and design as recorded, not drawing a conclusion about the presence, absence, size, or clinical importance of a drug interaction.

13. Why This Trial Matters Statistically

This study is statistically interesting because its question is about drug exposure under combinations of treatments, rather than a direct clinical efficacy outcome. The registered measures describe different aspects of APV pharmacokinetics: minimum and maximum concentrations, overall exposure, and apparent clearance. Considering several measures can provide a broader description of exposure, but it also makes clear why endpoint definitions and analysis priorities matter. The registry does not report those priorities or the results.

The arm descriptions also highlight the importance of regimen order. The record says matching groups received the same regimens in different orders and that their PK data were collated before assessment. In general, analyses of measurements collected across periods need to consider whether observations are dependent and whether order or period could matter. The registry does not report the model or how those issues were handled, so the design description alone cannot establish the validity or precision of the comparisons.

Another statistical lesson is the difference between a completed study and an interpretable result. The registry lists the study as completed and identifies a confidence-interval summary, but does not report estimates or analyses. Without them, readers cannot assess effect magnitude, uncertainty, or compatibility with a meaningful change. A planned endpoint and a stated interval method do not replace the observed results.

Finally, the record’s differing enrollment and regimen descriptions illustrate why transparent, consistent reporting matters. The registry lists 45 in its enrollment field and describes 48 in the brief summary; it also varies in its descriptions of periods and regimen duration. These inconsistencies are unresolved in the registry record. They limit how confidently a reader can reconstruct the analysis structure and relate the reported safety denominators to the intended study population.

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 principal limitation for interpretation is that the registry record reports no numerical primary-outcome results and lists zero analyses. Although the endpoint and confidence-interval summary are described, estimates, interval limits, and treatment contrasts are absent. The record therefore does not permit an assessment of effect size or precision.

There are internal differences in the study description. The title calls the study six-period, while the brief summary calls it six-arm and three-period, and the group descriptions list three periods. The title describes a 14-day RTG regimen, whereas the brief summary describes a 7-day RTG-alone regimen. The enrollment field lists 45, while the brief summary describes 48 healthy adults. These differences are not reconciled in the registry record and should not be resolved by assumption.

The record does not report the analysis model, analysis populations, missing-data methods, multiplicity approach, or treatment-contrast definitions. It also does not explain how repeated measurements, regimen order, or period effects were handled. The outcome description lists multiple PK measures, without specifying their hierarchy or how the results were intended to support a single conclusion.

The safety information is limited to group-level counts. No serious adverse-event terms are listed, and deaths are recorded as null rather than as a numerical count. Details about event timing, exposure, and ascertainment are not reported in the registry record. These reporting limitations constrain interpretation of both the pharmacokinetic and safety information; they do not establish what analyses or information may exist outside the registry.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Interaction Study to Assess Drug Levels in Fasting Healthy Adult Subjects — NCT00802074.
• Registry record last updated 2016-01-29; status last verified 2016-01.
• Results first posted 2016-01-29.
• 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 randomized, open-label study of APV pharmacokinetics during FPV-based regimens with and without concurrent RTG in healthy adults under fasting conditions. The planned measures include Cmin, Cmax, AUC, and CL/F, with a mean and 90% confidence interval specified for the primary outcome. The group descriptions pair corresponding regimens in different orders.

Numerical primary-outcome results and analyses are not reported in the registry record. The record also contains unresolved differences in its enrollment and study-period descriptions. Serious adverse-event entries list zero affected participants in each group; deaths are not reported in the registry record. The available information describes the registered question and design, but does not support a conclusion about the size or direction of a pharmacokinetic interaction.